"Item Id","Item URI","Dublin Core:Title","Dublin Core:Subject","Dublin Core:Description","Dublin Core:Creator","Dublin Core:Source","Dublin Core:Publisher","Dublin Core:Date","Dublin Core:Contributor","Dublin Core:Rights","Dublin Core:Relation","Dublin Core:Format","Dublin Core:Language","Dublin Core:Type","Dublin Core:Identifier","Dublin Core:Coverage","Item Type Metadata:Bibliography","Item Type Metadata:Biographical Text","Item Type Metadata:Occupation","Item Type Metadata:Death Date","Item Type Metadata:Birthplace","Item Type Metadata:Text","Item Type Metadata:Player","Item Type Metadata:Access","Item Type Metadata:Alternate URL","Item Type Metadata:Citation","Item Type Metadata:Accessibility","Item Type Metadata:Abstract","Item Type Metadata:Read Online","Item Type Metadata:Additional Exercise","Item Type Metadata:Email Body","Item Type Metadata:Interviewer","Item Type Metadata:Interviewee","Item Type Metadata:Location","Item Type Metadata:Transcription","Item Type Metadata:Local URL","Item Type Metadata:Original Format","Item Type Metadata:Physical Dimensions","Item Type Metadata:Duration","Item Type Metadata:Compression","Item Type Metadata:Producer","Item Type Metadata:Director","Item Type Metadata:Bit Rate/Frequency","Item Type Metadata:Time Summary","Item Type Metadata:Birth Date","Item Type Metadata:Subject Line","Item Type Metadata:From","Item Type Metadata:To","Item Type Metadata:CC","Item Type Metadata:BCC","Item Type Metadata:Number of Attachments","Item Type Metadata:Standards","Item Type Metadata:Objectives","Item Type Metadata:Materials","Item Type Metadata:Lesson Plan Text","Item Type Metadata:URL","Item Type Metadata:Event Type","Item Type Metadata:Participants","PDF Text:Text",tags,file,itemType,collection,public,featured
1743,https://repository.netecweb.org/items/show/1743,"Safety, tolerability, pharmacokinetics, and immunogenicity of a human monoclonal antibody targeting the G glycoprotein of henipaviruses in healthy adults: a first-in-human, randomised, controlled, phase 1 study",Laboratory,"The monoclonal antibody m102.4 is a potent, fully human antibody that neutralises Hendra and Nipah viruses in vitro and in vivo. We aimed to investigate the safety, tolerability, pharmacokinetics, and immunogenicity of m102.4 in healthy adults.","Playford, E. G., T. Munro, S. M. Mahler, S. Elliott, M. Gerometta, K. L. Hoger, M. L. Jones, P. Griffin, K. D. Lynch, H. Carroll, D. El Saadi, M. E. Gilmour, B. Hughes, K. Hughes, E. Huang, C. de Bakker, R. Klein, M. G. Scher, I. L. Smith, L. F. Wang, S. B. Lambert, D. S. Dimitrov, P. P. Gray, and C. C. Broder.",,,2020-04,,,,,,Publication,,2024-02-09,,,,,,,,,,"Playford, E. G., T. Munro, S. M. Mahler, S. Elliott, M. Gerometta, K. L. Hoger, M. L. Jones, P. Griffin, K. D. Lynch, H. Carroll, D. El Saadi, M. E. Gilmour, B. Hughes, K. Hughes, E. Huang, C. de Bakker, R. Klein, M. G. Scher, I. L. Smith, L. F. Wang, S. B. Lambert, D. S. Dimitrov, P. P. Gray, and C. C. Broder. 2020. ""Safety, tolerability, pharmacokinetics, and immunogenicity of a human monoclonal antibody targeting the G glycoprotein of henipaviruses in healthy adults: a first-in-human, randomised, controlled, phase 1 study."" Lancet Infect Dis 20 (4):445-454. doi: 10.1016/s1473-3099(19)30634-6.
","Pay online through the Lancet.","
Background: The monoclonal antibody m102.4 is a potent, fully human antibody that neutralises Hendra and Nipah viruses in vitro and in vivo. We aimed to investigate the safety, tolerability, pharmacokinetics, and immunogenicity of m102.4 in healthy adults.
Methods: In this double-blind, placebo-controlled, single-centre, dose-escalation, phase 1 trial of m102.4, we randomly assigned healthy adults aged 18-50 years with a body-mass index of 18·0-35·0 kg/m2 to one of five cohorts. A sentinel pair for each cohort was randomly assigned to either m102.4 or placebo. The remaining participants in each cohort were randomly assigned (5:1) to receive m102.4 or placebo. Cohorts 1-4 received a single intravenous infusion of m102.4 at doses of 1 mg/kg (cohort 1), 3 mg/kg (cohort 2), 10 mg/kg (cohort 3), and 20 mg/kg (cohort 4), and were monitored for 113 days. Cohort 5 received two infusions of 20 mg/kg 72 h apart and were monitored for 123 days. The primary outcomes were safety and tolerability. Secondary outcomes were pharmacokinetics and immunogenicity. Analyses were completed according to protocol. The study was registered on the Australian New Zealand Clinical Trials Registry, ACTRN12615000395538.
Findings: Between March 27, 2015, and June 16, 2016, 40 (52%) of 77 healthy screened adults were enrolled in the study. Eight participants were assigned to each cohort (six received m102.4 and two received placebo). 86 treatment-emergent adverse events were reported, with similar rates between placebo and treatment groups. The most common treatment-related event was headache (12 [40%] of 30 participants in the combined m102.4 group, and three [30%] of ten participants in the pooled placebo group). No deaths or severe adverse events leading to study discontinuation occurred. Pharmacokinetics based on those receiving m102.4 (n=30) were linear, with a median half-life of 663·3 h (range 474·3-735·1) for cohort 1, 466·3 h (382·8-522·3) for cohort 2, 397·0 h (333·9-491·8) for cohort 3, and 466·7 h (351·0-889·6) for cohort 4. The elimination kinetics of those receiving repeated dosing (cohort 5) were similar to those of single-dose recipients (median elimination half-time 472·0 [385·6-592·0]). Anti-m102.4 antibodies were not detected at any time-point during the study.
Interpretation: Single and repeated dosing of m102.4 were well tolerated and safe, displayed linear pharmacokinetics, and showed no evidence of an immunogenic response. This study will inform future dosing regimens for m102.4 to achieve prolonged exposure for systemic efficacy to prevent and treat henipavirus infections.
Funding: Queensland Department of Health, the National Health and Medical Research Council, and the National Hendra Virus Research Program.
Copyright © 2020 Elsevier Ltd. All rights reserved.
",https://www.thelancet.com/journals/laninf/article/PIIS1473-30991930634-6/fulltext,,,,,,,,,,,,,,,,,,,,,,,,,,,https://pubmed.ncbi.nlm.nih.gov/32027842/,,,,"Nipah (NiV),R-Res&Pub,R-T&C,Trial",,Publication,Discover,1,0
1225,https://repository.netecweb.org/items/show/1225,"Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report",Research,"Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death.","The RECOVERY Collaborative Group. ",,,2020-07-17,,,,,,Publication,,,,,,,,,,,,"The RECOVERY Collaborative Group. ""Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report."" 2020. New England Journal of Medicine.
","Free online on NEJM","Background
Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death.
Methods
In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison.
Results
A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55).
Conclusions
In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936. opens in new tab; ISRCTN number, 50189673. opens in new tab.)
",https://www.nejm.org/doi/full/10.1056/NEJMoa2021436,,,,,,,,,,,,,,,,,,,,,,,,,,,https://www.nejm.org/doi/full/10.1056/NEJMoa2021436,,,,"2019-nCoV,Coronavirus,COVID-19,R-Res&Pub,Therapeutics,Trial",https://repository.netecweb.org/files/original/99bceacb29370a100db317cb497e2afe.png,Publication,Discover,1,0
1226,https://repository.netecweb.org/items/show/1226,"Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial",Research,"The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2.","Oxford COVID Vaccine Trial Group","Folegatti, Pedro M., Katie J. Ewer, Parvinder K. Aley, Brian Angus, Stephan Becker, Sandra Belij-Rammerstorfer, Duncan Bellamy, Sagida Bibi, Mustapha Bittaye, Elizabeth A. Clutterbuck, Christina Dold, Saul N. Faust, Adam Finn, Amy L. Flaxman, Bassam Hallis, Paul Heath, Daniel Jenkin, Rajeka Lazarus, Rebecca Makinson, Angela M. Minassian, Katrina M. Pollock, Maheshi Ramasamy, Hannah Robinson, Matthew Snape, Richard Tarrant, Merryn Voysey, Catherine Green, Alexander D. Douglas, Adrian V. S. Hill, Teresa Lambe, Sarah C. Gilbert, Andrew J. Pollard, Jeremy Aboagye, Kelly Adams, Aabidah Ali, Elizabeth Allen, Jennifer L. Allison, Rachel Anslow, Edward H. Arbe-Barnes, Gavin Babbage, Kenneth Baillie, Megan Baker, Philip Baker, Ioana Baleanu, Juliana Ballaminut, Eleanor Barnes, Jordan Barrett, Louise Bates, Alexander Batten, Kirsten Beadon, Rebecca Beckley, Eleanor Berrie, Lisa Berry, Amy Beveridge, Kevin R. Bewley, Else Margreet Bijker, Tracey Bingham, Luke Blackwell, Caitlin L. Blundell, Emma Bolam, Elena Boland, Nicola Borthwick, Thomas Bower, Amy Boyd, Tanja Brenner, Philip D. Bright, Charlie Brown-O'Sullivan, Emily Brunt, Jamie Burbage, Sharon Burge, Karen R. Buttigieg, Nicholas Byard, Ingrid Cabera Puig, Anna Calvert, Susana Camara, Michelangelo Cao, Federica Cappuccini, Melanie Carr, Miles W. Carroll, Victoria Carter, Katrina Cathie, Ruth J. Challis, Irina Chelysheva, Jee-Sun Cho, Paola Cicconi, Liliana Cifuentes, Helen Clark, Elizabeth Clark, Tom Cole, Rachel Colin-Jones, Christopher P. Conlon, Aislinn Cook, Naomi S. Coombes, Rachel Cooper, Catherine A. Cosgrove, Karen Coy, Wendy E. M. Crocker, Christina J. Cunningham, Brad E. Damratoski, Lynne Dando, Mehreen S. Datoo, Hannah Davies, Hans De Graaf, Tesfaye Demissie, Claudio Di Maso, Isabelle Dietrich, Tao Dong, Francesca R. Donnellan, Naomi Douglas, Charlotte Downing, Jonathan Drake, Rachael Drake-Brockman, Ruth Elizabeth Drury, Susanna Jane Dunachie, Nick J. Edwards, Frances D. L. Edwards, Chris J. Edwards, Sean C. Elias, Michael J. Elmore, Katherine R. W. Emary, Marcus Rex English, Susanne Fagerbrink, Sally Felle, Shuo Feng, Samantha Field, Carine Fixmer, Clare Fletcher, Karen J. Ford, Jamie Fowler, Polly Fox, Emma Francis, John Frater, Julie Furze, Michelle Fuskova, Eva Galiza, Diane Gbesemete, Ciaran Gilbride, Giacomo Gorini, Lyndsey Goulston, Caroline Grabau, Lara Gracie, Zoe Gray, Lucy Belle Guthrie, Mark Hackett, Sandro Halwe, Elizabeth Hamilton, Joseph Hamlyn, Brama Hanumunthadu, Irasha Harding, Stephanie A. Harris, Andrew Harris, Daisy Harrison, Clare Harrison, Thomas C. Hart, Louise Haskell, Sophia Hawkins, Ian Head, John Aaron Henry, Jennifer Hill, Susanne H. C. Hodgson, Mimi M. Hou, Elizabeth Howe, Nicola Howell, Cecilia Hutlin, Sabina Ikram, Catherine Isitt, Poppy Iveson, Susan Jackson, Frederic Jackson, Sir William James, Megan Jenkins, Elizabeth Jones, Kathryn Jones, Christine E. Jones, Bryony Jones, Reshma Kailath, Konstantinos Karampatsas, Jade Keen, Sarah Kelly, Dearbhla Kelly, David Kerr, Simon Kerridge, Liaquat Khan, Uzma Khan, Annabel Killen, Jasmin Kinch, Thomas B. King, Lloyd King, Jade King, Lucy Kingham-Page, Paul Klenerman, Francesca Knapper, Julian C. Knight, Stanislava Koleva, Alexandra Kupke, Colin W. Larkworthy, Jessica P. J. Larwood, Anna Laskey, Alison M. Lawrie, Arlene Lee, Kim Yee Ngan Lee, Emily A. Lee, Helen Legge, Alice Lelliott, Nana-Marie Lemm, Amelia M. Lias, Aline Linder, Samuel Lipworth, Xinxue Liu, Shuchang Liu, Raquel Lopez Ramon, May Lwin, Francesca Mabesa, Meera Madhavan, Gary Mallett, Kushal Mansatta, Inēs Marcal, Spyridoula Marinou, Emma Marlow, Julia L. Marshall, Jane Martin, Joanne McEwan, Gretchen Meddaugh, Alexander J. Mentzer, Neginsadat Mirtorabi, Maria Moore, Edward Moran, Ella Morey, Victoria Morgan, Susan Jane Morris, Hazel Morrison, Gertraud Morshead, Richard Morter, Yama F. Mujadidi, Jilly Muller, Tatiana Munera-Huertas, Claire Munro, Alasdair Munro, Sarah Murphy, Vincent J. Muster, Philomena Mweu, Andrés Noé, Fay L. Nugent, Elizabeth Nugent, Katie O'Brien, Daniel O'Connor, Blanché Oguti, Jennifer L. Oliver, Catarina Oliveira, Peter John O'Reilly, Mairead Osborn, Piper Osborne, Cathy Owen, Daniel Owens, Nelly Owino, Mihaela Pacurar, Kaye Parker, Helena Parracho, Maia Patrick-Smith, Victoria Payne, Jennifer Pearce, Yanchun Peng, Marco Polo Peralta Alvarez, James Perring, Katja Pfafferott, Dimitra Pipini, Emma Plested, Helen Pluess-Hall, Katrina Pollock, Ian Poulton, Laura Presland, Samuel Provstgaard-Morys, David Pulido, Kajal Radia, Fernando Ramos Lopez, Jade Rand, Helen Ratcliffe, Thomas Rawlinson, Sarah Rhead, Amy Riddell, Adam John Ritchie, Hannah Roberts, Joanna Robson, Sophie Roche, Cornelius Rohde, Christine S. Rollier, Rosanna Romani, Indra Rudiansyah, Stephen Saich, Sara Sajjad, Stephannie Salvador, Lidia Sanchez Riera, Helen Sanders, Katherine Sanders, Shari Sapaun, Chloe Sayce, Ella Schofield, Gavin Screaton, Beatrice Selby, Calum Semple, Hannah R. Sharpe, Adam Shea, Holly Shelton, Sarah Silk, Laura Silva-Reyes, Donal T. Skelly, Heather Smee, Catherine C. Smith, David J. Smith, Rinn Song, Alexandra J. Spencer, Elizabeth Stafford, Amy Steele, Elena Stefanova, Lisa Stockdale, Anna Szigeti, Abdessamad Tahiri-Alaoui, Moira Tait, Helen Talbot, Rachel Tanner, Iona Jennifer Taylor, Victoria Taylor, Rebecca Te Water Naude, Nazia Thakur, Yrene Themistocleous, Andreas Themistocleous, Merin Thomas, Tonia M. Thomas, Amber Thompson, Samantha Thomson-Hill, Jennifer Tomlins, Susan Tonks, James Towner, Nguyen Tran, Julia A. Tree, Adam Truby, Kate Turkentine, Cheryl Turner, Nicola Turner, Sally Turner, Toby Tuthill, Marta Ulaszewska, Rachel Varughese, Neeltje Van Doremalen, Kristin Veighey, Marije K. Verheul, Iason Vichos, Elia Vitale, Laura Walker, Marion E. E. Watson, Benjamin Welham, Julie Wheat, Caroline White, Rachel White, Andrew T. Worth, Danny Wright, Suzie Wright, Xin Li Yao, and Yasmine Yau. ",,2020-07-20,,,,,,Publication,,,,,,,,,,,,"Folegatti, Pedro M., Katie J. Ewer, Parvinder K. Aley, Brian Angus, Stephan Becker, Sandra Belij-Rammerstorfer, Duncan Bellamy, Sagida Bibi, Mustapha Bittaye, Elizabeth A. Clutterbuck, Christina Dold, Saul N. Faust, Adam Finn, Amy L. Flaxman, Bassam Hallis, Paul Heath, Daniel Jenkin, Rajeka Lazarus, Rebecca Makinson, Angela M. Minassian, Katrina M. Pollock, Maheshi Ramasamy, Hannah Robinson, Matthew Snape, Richard Tarrant, Merryn Voysey, Catherine Green, Alexander D. Douglas, Adrian V. S. Hill, Teresa Lambe, Sarah C. Gilbert, Andrew J. Pollard, Jeremy Aboagye, Kelly Adams, Aabidah Ali, Elizabeth Allen, Jennifer L. Allison, Rachel Anslow, Edward H. Arbe-Barnes, Gavin Babbage, Kenneth Baillie, Megan Baker, Philip Baker, Ioana Baleanu, Juliana Ballaminut, Eleanor Barnes, Jordan Barrett, Louise Bates, Alexander Batten, Kirsten Beadon, Rebecca Beckley, Eleanor Berrie, Lisa Berry, Amy Beveridge, Kevin R. Bewley, Else Margreet Bijker, Tracey Bingham, Luke Blackwell, Caitlin L. Blundell, Emma Bolam, Elena Boland, Nicola Borthwick, Thomas Bower, Amy Boyd, Tanja Brenner, Philip D. Bright, Charlie Brown-O'Sullivan, Emily Brunt, Jamie Burbage, Sharon Burge, Karen R. Buttigieg, Nicholas Byard, Ingrid Cabera Puig, Anna Calvert, Susana Camara, Michelangelo Cao, Federica Cappuccini, Melanie Carr, Miles W. Carroll, Victoria Carter, Katrina Cathie, Ruth J. Challis, Irina Chelysheva, Jee-Sun Cho, Paola Cicconi, Liliana Cifuentes, Helen Clark, Elizabeth Clark, Tom Cole, Rachel Colin-Jones, Christopher P. Conlon, Aislinn Cook, Naomi S. Coombes, Rachel Cooper, Catherine A. Cosgrove, Karen Coy, Wendy E. M. Crocker, Christina J. Cunningham, Brad E. Damratoski, Lynne Dando, Mehreen S. Datoo, Hannah Davies, Hans De Graaf, Tesfaye Demissie, Claudio Di Maso, Isabelle Dietrich, Tao Dong, Francesca R. Donnellan, Naomi Douglas, Charlotte Downing, Jonathan Drake, Rachael Drake-Brockman, Ruth Elizabeth Drury, Susanna Jane Dunachie, Nick J. Edwards, Frances D. L. Edwards, Chris J. Edwards, Sean C. Elias, Michael J. Elmore, Katherine R. W. Emary, Marcus Rex English, Susanne Fagerbrink, Sally Felle, Shuo Feng, Samantha Field, Carine Fixmer, Clare Fletcher, Karen J. Ford, Jamie Fowler, Polly Fox, Emma Francis, John Frater, Julie Furze, Michelle Fuskova, Eva Galiza, Diane Gbesemete, Ciaran Gilbride, Giacomo Gorini, Lyndsey Goulston, Caroline Grabau, Lara Gracie, Zoe Gray, Lucy Belle Guthrie, Mark Hackett, Sandro Halwe, Elizabeth Hamilton, Joseph Hamlyn, Brama Hanumunthadu, Irasha Harding, Stephanie A. Harris, Andrew Harris, Daisy Harrison, Clare Harrison, Thomas C. Hart, Louise Haskell, Sophia Hawkins, Ian Head, John Aaron Henry, Jennifer Hill, Susanne H. C. Hodgson, Mimi M. Hou, Elizabeth Howe, Nicola Howell, Cecilia Hutlin, Sabina Ikram, Catherine Isitt, Poppy Iveson, Susan Jackson, Frederic Jackson, Sir William James, Megan Jenkins, Elizabeth Jones, Kathryn Jones, Christine E. Jones, Bryony Jones, Reshma Kailath, Konstantinos Karampatsas, Jade Keen, Sarah Kelly, Dearbhla Kelly, David Kerr, Simon Kerridge, Liaquat Khan, Uzma Khan, Annabel Killen, Jasmin Kinch, Thomas B. King, Lloyd King, Jade King, Lucy Kingham-Page, Paul Klenerman, Francesca Knapper, Julian C. Knight, Stanislava Koleva, Alexandra Kupke, Colin W. Larkworthy, Jessica P. J. Larwood, Anna Laskey, Alison M. Lawrie, Arlene Lee, Kim Yee Ngan Lee, Emily A. Lee, Helen Legge, Alice Lelliott, Nana-Marie Lemm, Amelia M. Lias, Aline Linder, Samuel Lipworth, Xinxue Liu, Shuchang Liu, Raquel Lopez Ramon, May Lwin, Francesca Mabesa, Meera Madhavan, Gary Mallett, Kushal Mansatta, Inēs Marcal, Spyridoula Marinou, Emma Marlow, Julia L. Marshall, Jane Martin, Joanne McEwan, Gretchen Meddaugh, Alexander J. Mentzer, Neginsadat Mirtorabi, Maria Moore, Edward Moran, Ella Morey, Victoria Morgan, Susan Jane Morris, Hazel Morrison, Gertraud Morshead, Richard Morter, Yama F. Mujadidi, Jilly Muller, Tatiana Munera-Huertas, Claire Munro, Alasdair Munro, Sarah Murphy, Vincent J. Muster, Philomena Mweu, Andrés Noé, Fay L. Nugent, Elizabeth Nugent, Katie O'Brien, Daniel O'Connor, Blanché Oguti, Jennifer L. Oliver, Catarina Oliveira, Peter John O'Reilly, Mairead Osborn, Piper Osborne, Cathy Owen, Daniel Owens, Nelly Owino, Mihaela Pacurar, Kaye Parker, Helena Parracho, Maia Patrick-Smith, Victoria Payne, Jennifer Pearce, Yanchun Peng, Marco Polo Peralta Alvarez, James Perring, Katja Pfafferott, Dimitra Pipini, Emma Plested, Helen Pluess-Hall, Katrina Pollock, Ian Poulton, Laura Presland, Samuel Provstgaard-Morys, David Pulido, Kajal Radia, Fernando Ramos Lopez, Jade Rand, Helen Ratcliffe, Thomas Rawlinson, Sarah Rhead, Amy Riddell, Adam John Ritchie, Hannah Roberts, Joanna Robson, Sophie Roche, Cornelius Rohde, Christine S. Rollier, Rosanna Romani, Indra Rudiansyah, Stephen Saich, Sara Sajjad, Stephannie Salvador, Lidia Sanchez Riera, Helen Sanders, Katherine Sanders, Shari Sapaun, Chloe Sayce, Ella Schofield, Gavin Screaton, Beatrice Selby, Calum Semple, Hannah R. Sharpe, Adam Shea, Holly Shelton, Sarah Silk, Laura Silva-Reyes, Donal T. Skelly, Heather Smee, Catherine C. Smith, David J. Smith, Rinn Song, Alexandra J. Spencer, Elizabeth Stafford, Amy Steele, Elena Stefanova, Lisa Stockdale, Anna Szigeti, Abdessamad Tahiri-Alaoui, Moira Tait, Helen Talbot, Rachel Tanner, Iona Jennifer Taylor, Victoria Taylor, Rebecca Te Water Naude, Nazia Thakur, Yrene Themistocleous, Andreas Themistocleous, Merin Thomas, Tonia M. Thomas, Amber Thompson, Samantha Thomson-Hill, Jennifer Tomlins, Susan Tonks, James Towner, Nguyen Tran, Julia A. Tree, Adam Truby, Kate Turkentine, Cheryl Turner, Nicola Turner, Sally Turner, Toby Tuthill, Marta Ulaszewska, Rachel Varughese, Neeltje Van Doremalen, Kristin Veighey, Marije K. Verheul, Iason Vichos, Elia Vitale, Laura Walker, Marion E. E. Watson, Benjamin Welham, Julie Wheat, Caroline White, Rachel White, Andrew T. Worth, Danny Wright, Suzie Wright, Xin Li Yao, and Yasmine Yau. 2020. ""Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial."" The Lancet.
","Free online on Lancet site.","
Background
The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2.
Methods
We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18–55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 10
10 viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT
50]; a microneutralisation assay [MNA
50, MNA
80, and MNA
90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and
ClinicalTrials.gov,
NCT04324606.
Findings
Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493–1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96–317; n=127), and were boosted following a second dose (639 EU, 360–792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R2=0·67 by Marburg VN; p<0·001).
Interpretation
ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support large-scale evaluation of this candidate vaccine in an ongoing phase 3 programme.
Funding
UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and the German Center for Infection Research (DZIF), Partner site Gießen-Marburg-Langen.
",https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31604-4/fulltext,,,,,,,,,,,,,,,,,,,,,,,,,,,https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31604-4/fulltext,,,,"2019-nCoV,Coronavirus,COVID-19,R-Res&Pub,Trial,Vaccine Study",https://repository.netecweb.org/files/original/2a508e63261e9c91b88fe0e077f44e2a.png,Publication,Discover,1,0
1227,https://repository.netecweb.org/items/show/1227,"Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial",Research,"This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose of the candidate vaccine for an efficacy study.","Zhu, Feng-Cai, Xu-Hua Guan, Yu-Hua Li, Jian-Ying Huang, Tao Jiang, Li-Hua Hou, Jing-Xin Li, Bei-Fang Yang, Ling Wang, Wen-Juan Wang, Shi-Po Wu, Zhao Wang, Xiao-Hong Wu, Jun-Jie Xu, Zhe Zhang, Si-Yue Jia, Bu-Sen Wang, Yi Hu, Jing-Jing Liu, Jun Zhang, Xiao-Ai Qian, Qiong Li, Hong-Xing Pan, Hu-Dachuan Jiang, Peng Deng, Jin-Bo Gou, Xue-Wen Wang, Xing-Huan Wang, and Wei Chen. ",,,2020-07-20,,,,,,Publication,,,,,,,,,,,,"Zhu, Feng-Cai, Xu-Hua Guan, Yu-Hua Li, Jian-Ying Huang, Tao Jiang, Li-Hua Hou, Jing-Xin Li, Bei-Fang Yang, Ling Wang, Wen-Juan Wang, Shi-Po Wu, Zhao Wang, Xiao-Hong Wu, Jun-Jie Xu, Zhe Zhang, Si-Yue Jia, Bu-Sen Wang, Yi Hu, Jing-Jing Liu, Jun Zhang, Xiao-Ai Qian, Qiong Li, Hong-Xing Pan, Hu-Dachuan Jiang, Peng Deng, Jin-Bo Gou, Xue-Wen Wang, Xing-Huan Wang, and Wei Chen. 2020. ""Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial."" The Lancet.
","Free online on Lancet site.","
Background
This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose of the candidate vaccine for an efficacy study.
Methods
This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 10
11 viral particles per mL or 5 × 10
10 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with
ClinicalTrials.gov,
NCT04341389.
Findings
603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). In the 1 × 1011 and 5 × 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2–749·2) and 571·0 (467·6–697·3), with seroconversion rates at 96% (95% CI 93–98) and 97% (92–99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8–22·7) and 18·3 (14·4–23·3) in participants receiving 1 × 1011 and 5 × 1010 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85–93) of 253 and 113 (88%, 81–92) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 1011 viral particles dose group and one (1%) participant in the 5 × 1010 viral particles dose group. No serious adverse reactions were documented.
Interpretation
The Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation.
Funding
National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.
",https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31605-6/fulltext,,,,,,,,,,,,,,,,,,,,,,,,,,,https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31605-6/fulltext,,,,"2019-nCoV,Coronavirus,COVID-19,R-Res&Pub,Trial,Vaccine Study",https://repository.netecweb.org/files/original/c8fee0a5ec3bded7ec724307c84b54a8.png,Publication,Discover,1,0
1231,https://repository.netecweb.org/items/show/1231,"The RECOVERY Platform","Treatment & Care","In a platform trial, patients with a single disease are randomly assigned to a group of different therapies on the basis of a decision algorithm to determine whether any therapy has benefit.","Normand, Sharon-Lise T. ",,,2020-07-21,"2022-09-27 - general asset review - Treatment & Care group",,,,,Publication,,2023-09-27,,,,,,,,,,"Normand, Sharon-Lise T. 2020. ""The RECOVERY Platform."" New England Journal of Medicine.
","Free online on NEJM",,https://www.nejm.org/doi/full/10.1056/NEJMe2025674,,,,,,,,,,,,,,,,,,,,,,,,,,,https://www.nejm.org/doi/full/10.1056/NEJMe2025674,,,,"2019-nCoV,Coronavirus,COVID-19,R-Res&Pub,R-T&C,Therapeutics,Trial",https://repository.netecweb.org/files/original/473c025315cfa7786c5e943c4aeb084a.png,Publication,Discover,1,0
1266,https://repository.netecweb.org/items/show/1266,"A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19",Research,"This reports on a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis.","Boulware, David R., Matthew F. Pullen, Ananta S. Bangdiwala, Katelyn A. Pastick, Sarah M. Lofgren, Elizabeth C. Okafor, Caleb P. Skipper, Alanna A. Nascene, Melanie R. Nicol, Mahsa Abassi, Nicole W. Engen, Matthew P. Cheng, Derek LaBar, Sylvain A. Lother, Lauren J. MacKenzie, Glen Drobot, Nicole Marten, Ryan Zarychanski, Lauren E. Kelly, Ilan S. Schwartz, Emily G. McDonald, Radha Rajasingham, Todd C. Lee, and Kathy H. Hullsiek. ",,,2020-08-06,,,,,,Publication,,,,,,,,,,,,"Boulware, David R., Matthew F. Pullen, Ananta S. Bangdiwala, Katelyn A. Pastick, Sarah M. Lofgren, Elizabeth C. Okafor, Caleb P. Skipper, Alanna A. Nascene, Melanie R. Nicol, Mahsa Abassi, Nicole W. Engen, Matthew P. Cheng, Derek LaBar, Sylvain A. Lother, Lauren J. MacKenzie, Glen Drobot, Nicole Marten, Ryan Zarychanski, Lauren E. Kelly, Ilan S. Schwartz, Emily G. McDonald, Radha Rajasingham, Todd C. Lee, and Kathy H. Hullsiek. 2020. ""A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19."" New England Journal of Medicine 383 (6):517-25.
","Free online on NEJM","Background
Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown.
Methods
We conducted a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis. We enrolled adults who had household or occupational exposure to someone with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days). The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days.
Results
We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was −2.4 percentage points (95% confidence interval, −7.0 to 2.2; P=0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported.
Conclusions
After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure. (Funded by David Baszucki and Jan Ellison Baszucki and others; ClinicalTrials.gov number, NCT04308668. opens in new tab.)
",https://www.nejm.org/doi/full/10.1056/NEJMoa2016638,,,,,,,,,,,,,,,,,,,,,,,,,,,https://www.nejm.org/doi/full/10.1056/NEJMoa2016638,,,,"2019-nCoV,Clinical Trial,Coronavirus,COVID-19,Outcomes,R-Res&Pub,Research,Therapeutics,Trial",https://repository.netecweb.org/files/original/111dee0563894d304072e95e7faa5da8.png,Publication,Discover,1,0
1398,https://repository.netecweb.org/items/show/1398,"Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18–59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial",Laboratory,"With the unprecedented morbidity and mortality associated with the COVID-19 pandemic, a vaccine against COVID-19 is urgently needed. We investigated CoronaVac (Sinovac Life Sciences, Beijing, China), an inactivated vaccine candidate against COVID-19, containing inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for its safety, tolerability and immunogenicity.","Zhang, Yanjun, Gang Zeng, Hongxing Pan, Changgui Li, Yaling Hu, Kai Chu, Weixiao Han, Zhen Chen, Rong Tang, Weidong Yin, Xin Chen, Yuansheng Hu, Xiaoyong Liu, Congbing Jiang, Jingxin Li, Minnan Yang, Yan Song, Xiangxi Wang, Qiang Gao, and Fengcai Zhu. ",,,2020-11-17,"2023-12-18 skipped for review by Lab, bump to next round",,,,,Publication,Laboratory,2024-04-01,,,,,,,,,,"Zhang, Yanjun, Gang Zeng, Hongxing Pan, Changgui Li, Yaling Hu, Kai Chu, Weixiao Han, Zhen Chen, Rong Tang, Weidong Yin, Xin Chen, Yuansheng Hu, Xiaoyong Liu, Congbing Jiang, Jingxin Li, Minnan Yang, Yan Song, Xiangxi Wang, Qiang Gao, and Fengcai Zhu. 2020. ""Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial."" The Lancet Infectious Diseases.
","Free online on Lancet site.","Summary
Background
With the unprecedented morbidity and mortality associated with the COVID-19 pandemic, a vaccine against COVID-19 is urgently needed. We investigated CoronaVac (Sinovac Life Sciences, Beijing, China), an inactivated vaccine candidate against COVID-19, containing inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for its safety, tolerability and immunogenicity.
Methods
In this randomised, double-blind, placebo-controlled, phase 1/2 clinical trial, healthy adults aged 18–59 years were recruited from the community in Suining County of Jiangsu province, China. Adults with SARS-CoV-2 exposure or infection history, with axillary temperature above 37·0°C, or an allergic reaction to any vaccine component were excluded. The experimental vaccine for the phase 1 trial was manufactured using a cell factory process (CellSTACK Cell Culture Chamber 10, Corning, Wujiang, China), whereas those for the phase 2 trial were produced through a bioreactor process (ReadyToProcess WAVE 25, GE, Umea, Sweden). The phase 1 trial was done in a dose-escalating manner. At screening, participants were initially separated (1:1), with no specific randomisation, into two vaccination schedule cohorts, the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and within each cohort the first 36 participants were assigned to block 1 (low dose CoronaVac [3 μg per 0·5 mL of aluminium hydroxide diluent per dose) then another 36 were assigned to block 2 (high-dose Coronavc [6 μg per 0·5 mL of aluminium hydroxide diluent per dse]). Within each block, participants were randomly assigned (2:1), using block randomisation with a block size of six, to either two doses of CoronaVac or two doses of placebo. In the phase 2 trial, at screening, participants were initially separated (1:1), with no specific randomisation, into the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and participants were randomly assigned (2:2:1), using block randomisation with a block size of five, to receive two doses of either low-dose CoronaVac, high-dose CoronaVac, or placebo. Participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was adverse reactions within 28 days after injection in all participants who were given at least one dose of study drug (safety population). The primary immunogenic outcome was seroconversion rates of neutralising antibodies to live SARS-CoV-2 at day 14 after the last dose in the days 0 and 14 cohort, and at day 28 after the last dose in the days 0 and 28 cohort in participants who completed their allocated two-dose vaccination schedule (per-protocol population). This trial is registered with
ClinicalTrials.gov,
NCT04352608, and is closed to accrual.
Findings
Between April 16 and April 25, 2020, 144 participants were enrolled in the phase 1 trial, and between May 3 and May 5, 2020, 600 participants were enrolled in the phase 2 trial. 743 participants received at least one dose of investigational product (n=143 for phase 1 and n=600 for phase 2; safety population). In the phase 1 trial, the incidence of adverse reactions for the days 0 and 14 cohort was seven (29%) of 24 participants in the 3 ug group, nine (38%) of 24 in the 6 μg group, and two (8%) of 24 in the placebo group, and for the days 0 and 28 cohort was three (13%) of 24 in the 3 μg group, four (17%) of 24 in the 6 μg group, and three (13%) of 23 in the placebo group. The seroconversion of neutralising antibodies on day 14 after the days 0 and 14 vaccination schedule was seen in 11 (46%) of 24 participants in the 3 μg group, 12 (50%) of 24 in the 6 μg group, and none (0%) of 24 in the placebo group; whereas at day 28 after the days 0 and 28 vaccination schedule, seroconversion was seen in 20 (83%) of 24 in the 3 μg group, 19 (79%) of 24 in the 6 μg group, and one (4%) of 24 in the placebo group. In the phase 2 trial, the incidence of adverse reactions for the days 0 and 14 cohort was 40 (33%) of 120 participants in the 3 μg group, 42 (35%) of 120 in the 6 μg group, and 13 (22%) of 60 in the placebo group, and for the days 0 and 28 cohort was 23 (19%) of 120 in the 3 μg group, 23 (19%) of 120 in the 6 μg group, and 11 (18%) of 60 for the placebo group. Seroconversion of neutralising antibodies was seen for 109 (92%) of 118 participants in the 3 μg group, 117 (98%) of 119 in the 6 μg group, and two (3%) of 60 in the placebo group at day 14 after the days 0 and 14 schedule; whereas at day 28 after the days 0 and 28 schedule, seroconversion was seen in 114 (97%) of 117 in the 3 μg group, 118 (100%) of 118 in the 6 μg group, and none (0%) of 59 in the placebo group.
Interpretation
Taking safety, immunogenicity, and production capacity into account, the 3 μg dose of CoronaVac is the suggested dose for efficacy assessment in future phase 3 trials.
Funding
Chinese National Key Research and Development Program and Beijing Science and Technology Program.
",https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30843-4/fulltext,,,,,,,,,,,,,,,,,,,,,,,,,,,https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30843-4/fulltext,,,,"2019-nCoV,Coronavirus,COVID-19,R-Lab,R-Res&Pub,SARS-CoV-2,Trial,Vaccine Study",https://repository.netecweb.org/files/original/56764a8bdc1a871e4d2faed591677b2c.png,Publication,Discover,1,0
1487,https://repository.netecweb.org/items/show/1487,"Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials",Research,"The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. ","the Oxford COVID Vaccine Trial Group","Voysey, Merryn, Sue Ann Costa Clemens, Shabir A. Madhi, Lily Y. Weckx, Pedro M. Folegatti, Parvinder K. Aley, Brian Angus, Vicky L. Baillie, Shaun L. Barnabas, Qasim E. Bhorat, Sagida Bibi, Carmen Briner, Paola Cicconi, Elizabeth A. Clutterbuck, Andrea M. Collins, Clare L. Cutland, Thomas C. Darton, Keertan Dheda, Christina Dold, Christopher J. A. Duncan, Katherine R. W. Emary, Katie J. Ewer, Amy Flaxman, Lee Fairlie, Saul N. Faust, Shuo Feng, Daniela M. Ferreira, Adam Finn, Eva Galiza, Anna L. Goodman, Catherine M. Green, Christopher A. Green, Melanie Greenland, Catherine Hill, Helen C. Hill, Ian Hirsch, Alane Izu, Daniel Jenkin, Carina C. D. Joe, Simon Kerridge, Anthonet Koen, Gaurav Kwatra, Rajeka Lazarus, Vincenzo Libri, Patrick J. Lillie, Natalie G. Marchevsky, Richard P. Marshall, Ana V. A. Mendes, Eveline P. Milan, Angela M. Minassian, Alastair McGregor, Yama F. Mujadidi, Anusha Nana, Sherman D. Padayachee, Daniel J. Phillips, Ana Pittella, Emma Plested, Katrina M. Pollock, Maheshi N. Ramasamy, Adam J. Ritchie, Hannah Robinson, Alexandre V. Schwarzbold, Andrew Smith, Rinn Song, Matthew D. Snape, Eduardo Sprinz, Rebecca K. Sutherland, Emma C. Thomson, M. Estée Török, Mark Toshner, David P. J. Turner, Johan Vekemans, Tonya L. Villafana, Thomas White, Christopher J. Williams, Alexander D. Douglas, Adrian V. S. Hill, Teresa Lambe, Sarah C. Gilbert, and Andrew J. Pollard. ",,2021-02-19,,,,,,Publication,,,,,,,,,,,,"Voysey, Merryn, Sue Ann Costa Clemens, Shabir A. Madhi, Lily Y. Weckx, Pedro M. Folegatti, Parvinder K. Aley, Brian Angus, Vicky L. Baillie, Shaun L. Barnabas, Qasim E. Bhorat, Sagida Bibi, Carmen Briner, Paola Cicconi, Elizabeth A. Clutterbuck, Andrea M. Collins, Clare L. Cutland, Thomas C. Darton, Keertan Dheda, Christina Dold, Christopher J. A. Duncan, Katherine R. W. Emary, Katie J. Ewer, Amy Flaxman, Lee Fairlie, Saul N. Faust, Shuo Feng, Daniela M. Ferreira, Adam Finn, Eva Galiza, Anna L. Goodman, Catherine M. Green, Christopher A. Green, Melanie Greenland, Catherine Hill, Helen C. Hill, Ian Hirsch, Alane Izu, Daniel Jenkin, Carina C. D. Joe, Simon Kerridge, Anthonet Koen, Gaurav Kwatra, Rajeka Lazarus, Vincenzo Libri, Patrick J. Lillie, Natalie G. Marchevsky, Richard P. Marshall, Ana V. A. Mendes, Eveline P. Milan, Angela M. Minassian, Alastair McGregor, Yama F. Mujadidi, Anusha Nana, Sherman D. Padayachee, Daniel J. Phillips, Ana Pittella, Emma Plested, Katrina M. Pollock, Maheshi N. Ramasamy, Adam J. Ritchie, Hannah Robinson, Alexandre V. Schwarzbold, Andrew Smith, Rinn Song, Matthew D. Snape, Eduardo Sprinz, Rebecca K. Sutherland, Emma C. Thomson, M. Estée Török, Mark Toshner, David P. J. Turner, Johan Vekemans, Tonya L. Villafana, Thomas White, Christopher J. Williams, Alexander D. Douglas, Adrian V. S. Hill, Teresa Lambe, Sarah C. Gilbert, and Andrew J. Pollard. 2021. ""Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials."" The Lancet.
","Open Access on Lancet Site.","
Background
The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered.
Methods
We present data from three single-blind randomised controlled trials—one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)—and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 10
10 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 10
10 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and
ClinicalTrials.gov,
NCT04324606 (COV001),
NCT04400838 (COV002), and
NCT04444674 (COV005).
Findings
Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4–74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3–85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59–0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3–91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0–69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18–55 years (GMR 2·32 [2·01–2·68]).
Interpretation
The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose.
Funding
UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D’Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.
",https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00432-3/fulltext,,,,,,,,,,,,,,,,,,,,,,,,,,,https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00432-3/fulltext,,,,"2019-nCoV,Coronavirus,COVID-19,R-Res&Pub,Trial,Vaccine Study",,Publication,Discover,1,0
1504,https://repository.netecweb.org/items/show/1504,"Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial",Research,"BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine (3 μg or 6 μg) formulated with a toll-like receptor 7/8 agonist molecule (IMDG) adsorbed to alum (Algel). We previously reported findings from a double-blind, multicentre, randomised, controlled phase 1 trial on the safety and immunogenicity of three different formulations of BBV152 (3 μg with Algel-IMDG, 6 μg with Algel-IMDG, or 6 μg with Algel) and one Algel-only control (no antigen), with the first dose administered on day 0 and the second dose on day 14.","Ella, Raches, Siddharth Reddy, Harsh Jogdand, Vamshi Sarangi, Brunda Ganneru, Sai Prasad, Dipankar Das, Dugyala Raju, Usha Praturi, Gajanan Sapkal, Pragya Yadav, Prabhakar Reddy, Savita Verma, Chandramani Singh, Sagar Vivek Redkar, Chandra Sekhar Gillurkar, Jitendra Singh Kushwaha, Satyajit Mohapatra, Amit Bhate, Sanjay Rai, Samiran Panda, Priya Abraham, Nivedita Gupta, Krishna Ella, Balram Bhargava, and Krishna Mohan Vadrevu. ",,,2021-03-08,,,,,,Publication,,,,,,,,,,,,"Ella, Raches, Siddharth Reddy, Harsh Jogdand, Vamshi Sarangi, Brunda Ganneru, Sai Prasad, Dipankar Das, Dugyala Raju, Usha Praturi, Gajanan Sapkal, Pragya Yadav, Prabhakar Reddy, Savita Verma, Chandramani Singh, Sagar Vivek Redkar, Chandra Sekhar Gillurkar, Jitendra Singh Kushwaha, Satyajit Mohapatra, Amit Bhate, Sanjay Rai, Samiran Panda, Priya Abraham, Nivedita Gupta, Krishna Ella, Balram Bhargava, and Krishna Mohan Vadrevu. 2021. ""Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial."" The Lancet Infectious Diseases.
","Free online on Lancet site.","
Background
BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine (3 μg or 6 μg) formulated with a toll-like receptor 7/8 agonist molecule (IMDG) adsorbed to alum (Algel). We previously reported findings from a double-blind, multicentre, randomised, controlled phase 1 trial on the safety and immunogenicity of three different formulations of BBV152 (3 μg with Algel-IMDG, 6 μg with Algel-IMDG, or 6 μg with Algel) and one Algel-only control (no antigen), with the first dose administered on day 0 and the second dose on day 14. The 3 μg and 6 μg with Algel-IMDG formulations were selected for this phase 2 study. Herein, we report interim findings of the phase 2 trial on the immunogenicity and safety of BBV152, with the first dose administered on day 0 and the second dose on day 28.
Methods
We did a double-blind, randomised, multicentre, phase 2 clinical trial to evaluate the immunogenicity and safety of BBV152 in healthy adults and adolescents (aged 12–65 years) at nine hospitals in India. Participants with positive SARS-CoV-2 nucleic acid and serology tests were excluded. Participants were randomly assigned (1:1) to receive either 3 μg with Algel-IMDG or 6 μg with Algel-IMDG. Block randomisation was done by use of an interactive web response system. Participants, investigators, study coordinators, study-related personnel, and the sponsor were masked to treatment group allocation. Two intramuscular doses of vaccine were administered on day 0 and day 28. The primary outcome was SARS-CoV-2 wild-type neutralising antibody titres and seroconversion rates (defined as a post-vaccination titre that was at least four-fold higher than the baseline titre) at 4 weeks after the second dose (day 56), measured by use of the plaque-reduction neutralisation test (PRNT
50) and the microneutralisation test (MNT
50). The primary outcome was assessed in all participants who had received both doses of the vaccine. Cell-mediated responses were a secondary outcome and were assessed by T-helper-1 (Th1)/Th2 profiling at 2 weeks after the second dose (day 42). Safety was assessed in all participants who received at least one dose of the vaccine. In addition, we report immunogenicity results from a follow-up blood draw collected from phase 1 trial participants at 3 months after they received the second dose (day 104). This trial is registered at
ClinicalTrials.gov,
NCT04471519.
Findings
Between Sept 5 and 12, 2020, 921 participants were screened, of whom 380 were enrolled and randomly assigned to the 3 μg with Algel-IMDG group (n=190) or 6 μg with Algel-IMDG group (n=190). Geometric mean titres (GMTs; PRNT50) at day 56 were significantly higher in the 6 μg with Algel-IMDG group (197·0 [95% CI 155·6–249·4]) than the 3 μg with Algel-IMDG group (100·9 [74·1–137·4]; p=0·0041). Seroconversion based on PRNT50 at day 56 was reported in 171 (92·9% [95% CI 88·2–96·2] of 184 participants in the 3 μg with Algel-IMDG group and 174 (98·3% [95·1–99·6]) of 177 participants in the 6 μg with Algel-IMDG group. GMTs (MNT50) at day 56 were 92·5 (95% CI 77·7–110·2) in the 3 μg with Algel-IMDG group and 160·1 (135·8–188·8) in the 6 μg with Algel-IMDG group. Seroconversion based on MNT50 at day 56 was reported in 162 (88·0% [95% CI 82·4–92·3]) of 184 participants in the 3 μg with Algel-IMDG group and 171 (96·6% [92·8–98·8]) of 177 participants in the 6 μg with Algel-IMDG group. The 3 μg with Algel-IMDG and 6 μg with Algel-IMDG formulations elicited T-cell responses that were biased to a Th1 phenotype at day 42. No significant difference in the proportion of participants who had a solicited local or systemic adverse reaction in the 3 μg with Algel-IMDG group (38 [20·0%; 95% CI 14·7–26·5] of 190) and the 6 μg with Algel-IMDG group (40 [21·1%; 15·5–27·5] of 190) was observed on days 0–7 and days 28–35; no serious adverse events were reported in the study. From the phase 1 trial, 3-month post-second-dose GMTs (MNT50) were 39·9 (95% CI 32·0–49·9) in the 3μg with Algel-IMDG group, 69·5 (53·7–89·9) in the 6 μg with Algel-IMDG group, 53·3 (40·1–71·0) in the 6 μg with Algel group, and 20·7 (14·5–29·5) in the Algel alone group.
Interpretation
In the phase 1 trial, BBV152 induced high neutralising antibody responses that remained elevated in all participants at 3 months after the second vaccination. In the phase 2 trial, BBV152 showed better reactogenicity and safety outcomes, and enhanced humoral and cell-mediated immune responses compared with the phase 1 trial. The 6 μg with Algel-IMDG formulation has been selected for the phase 3 efficacy trial.
Funding
Bharat Biotech International.
Translation
For the Hindi translation of the abstract see Supplementary Materials section.
",https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00070-0/fulltext,,,,,,,,,,,,,,,,,,,,,,,,,,,https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00070-0/fulltext,,,,"2019-nCoV,Clinical Trial,Coronavirus,COVID-19,Immunology,R-Res&Pub,Trial,Vaccine Study",,Publication,Discover,1,0
1537,https://repository.netecweb.org/items/show/1537,"Safety and immunogenicity of an MF59-adjuvanted spike glycoprotein-clamp vaccine for SARS-CoV-2: a randomised, double-blind, placebo-controlled, phase 1 trial",Research,"Given the scale of the ongoing COVID-19 pandemic, the development of vaccines based on different platforms is essential, particularly in light of emerging viral variants, the absence of information on vaccine-induced immune durability, and potential paediatric use. We aimed to assess the safety and immunogenicity of an MF59-adjuvanted subunit vaccine for COVID-19 based on recombinant SARS-CoV-2 spike glycoprotein stabilised in a pre-fusion conformation by a novel molecular clamp (spike glycoprotein-clamp [sclamp]).","Chappell, Keith J., Francesca L. Mordant, Zheyi Li, Danushka K. Wijesundara, Paula Ellenberg, Julia A. Lackenby, Stacey T. M. Cheung, Naphak Modhiran, Michael S. Avumegah, Christina L. Henderson, Kym Hoger, Paul Griffin, Jillian Bennet, Luca Hensen, Wuji Zhang, Thi H. O. Nguyen, Sara Marrero-Hernandez, Kevin J. Selva, Amy W. Chung, Mai H. Tran, Peter Tapley, James Barnes, Patrick C. Reading, Suellen Nicholson, Stavroula Corby, Thomas Holgate, Bruce D. Wines, P. Mark Hogarth, Katherine Kedzierska, Damian F. J. Purcell, Charani Ranasinghe, Kanta Subbarao, Daniel Watterson, Paul R. Young, and Trent P. Munro.",,,2021-04-19,,,,,,Publication,,,,,,,,,,,,"Chappell, Keith J., Francesca L. Mordant, Zheyi Li, Danushka K. Wijesundara, Paula Ellenberg, Julia A. Lackenby, Stacey T. M. Cheung, Naphak Modhiran, Michael S. Avumegah, Christina L. Henderson, Kym Hoger, Paul Griffin, Jillian Bennet, Luca Hensen, Wuji Zhang, Thi H. O. Nguyen, Sara Marrero-Hernandez, Kevin J. Selva, Amy W. Chung, Mai H. Tran, Peter Tapley, James Barnes, Patrick C. Reading, Suellen Nicholson, Stavroula Corby, Thomas Holgate, Bruce D. Wines, P. Mark Hogarth, Katherine Kedzierska, Damian F. J. Purcell, Charani Ranasinghe, Kanta Subbarao, Daniel Watterson, Paul R. Young, and Trent P. Munro. 2021. ""Safety and immunogenicity of an MF59-adjuvanted spike glycoprotein-clamp vaccine for SARS-CoV-2: a randomised, double-blind, placebo-controlled, phase 1 trial."" The Lancet Infectious Diseases.
","Free online on Lancet site.","
Background
Given the scale of the ongoing COVID-19 pandemic, the development of vaccines based on different platforms is essential, particularly in light of emerging viral variants, the absence of information on vaccine-induced immune durability, and potential paediatric use. We aimed to assess the safety and immunogenicity of an MF59-adjuvanted subunit vaccine for COVID-19 based on recombinant SARS-CoV-2 spike glycoprotein stabilised in a pre-fusion conformation by a novel molecular clamp (spike glycoprotein-clamp [sclamp]).
Methods
We did a phase 1, double-blind, placebo-controlled, block-randomised trial of the sclamp subunit vaccine in a single clinical trial site in Brisbane, QLD, Australia. Healthy adults (aged ≥18 to ≤55 years) who had tested negative for SARS-CoV-2, reported no close contact with anyone with active or previous SARS-CoV-2 infection, and tested negative for pre-existing SARS-CoV-2 immunity were included. Participants were randomly assigned to one of five treatment groups and received two doses via intramuscular injection 28 days apart of either placebo, sclamp vaccine at 5 μg, 15 μg, or 45 μg, or one dose of sclamp vaccine at 45 μg followed by placebo. Participants and study personnel, except the dose administration personnel, were masked to treatment. The primary safety endpoints included solicited local and systemic adverse events in the 7 days after each dose and unsolicited adverse events up to 12 months after dosing. Here, data are reported up until day 57. Primary immunogenicity endpoints were antigen-specific IgG ELISA and SARS-CoV-2 microneutralisation assays assessed at 28 days after each dose. The study is ongoing and registered with
ClinicalTrials.gov,
NCT04495933.
Findings
Between June 23, 2020, and Aug 17, 2020, of 314 healthy volunteers screened, 120 were randomly assigned (n=24 per group), and 114 (95%) completed the study up to day 57 (mean age 32·5 years [SD 10·4], 65 [54%] male, 55 [46%] female). Severe solicited reactions were infrequent and occurred at similar rates in participants receiving placebo (two [8%] of 24) and the SARS-CoV-2 sclamp vaccine at any dose (three [3%] of 96). Both solicited reactions and unsolicited adverse events occurred at a similar frequency in participants receiving placebo and the SARS-CoV-2 sclamp vaccine. Solicited reactions occurred in 19 (79%) of 24 participants receiving placebo and 86 (90%) of 96 receiving the SARS-CoV-2 sclamp vaccine at any dose. Unsolicited adverse events occurred in seven (29%) of 24 participants receiving placebo and 35 (36%) of 96 participants receiving the SARS-CoV-2 sclamp vaccine at any dose. Vaccination with SARS-CoV-2 sclamp elicited a similar antigen-specific response irrespective of dose: 4 weeks after the initial dose (day 29) with 5 μg dose (geometric mean titre [GMT] 6400, 95% CI 3683–11 122), with 15 μg dose (7492, 4959–11 319), and the two 45 μg dose cohorts (8770, 5526–13 920 in the two-dose 45 μg cohort; 8793, 5570–13 881 in the single-dose 45 μg cohort); 4 weeks after the second dose (day 57) with two 5 μg doses (102 400, 64 857–161 676), with two 15 μg doses (74 725, 51 300–108 847), with two 45 μg doses (79 586, 55 430–114 268), only a single 45 μg dose (4795, 2858–8043). At day 57, 67 (99%) of 68 participants who received two doses of sclamp vaccine at any concentration produced a neutralising immune response, compared with six (25%) of 24 who received a single 45 μg dose and none of 22 who received placebo. Participants receiving two doses of sclamp vaccine elicited similar neutralisation titres, irrespective of dose: two 5 μg doses (GMT 228, 95% CI 146–356), two 15 μg doses (230, 170–312), and two 45 μg doses (239, 187–307).
Interpretation
This first-in-human trial shows that a subunit vaccine comprising mammalian cell culture-derived, MF59-adjuvanted, molecular clamp-stabilised recombinant spike protein elicits strong immune responses with a promising safety profile. However, the glycoprotein 41 peptide present in the clamp created HIV diagnostic assay interference, a possible barrier to widespread use highlighting the criticality of potential non-spike directed immunogenicity during vaccine development. Studies are ongoing with alternative molecular clamp trimerisation domains to ameliorate this response.
Funding
Coalition for Epidemic Preparedness Innovations, National Health and Medical Research Council, Queensland Government, and further philanthropic sources listed in the acknowledgments.
",https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00200-0/fulltext,,,,,,,,,,,,,,,,,,,,,,,,,,,https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00200-0/fulltext,,,,"2019-nCoV,Coronavirus,COVID-19,R-Res&Pub,Trial,Vaccine Study",,Publication,Discover,1,0
1687,https://repository.netecweb.org/items/show/1687,"Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial","Treatment & Care","Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19.","ACTT- Study Group","Cameron R Wolfe, Kay M Tomashek, Thomas F Patterson, Carlos A Gomez, Vincent C Marconi, Mamta K Jain, Otto O Yang, Catharine I Paules, Guillermo M Ruiz Palacios, Robert Grossberg, Michelle S Harkins, Richard A Mularski, Nathaniel Erdmann, Uriel Sandkovsky, Eyad Almasri, Justino Regalado Pineda, Alexandra W Dretler, Diego Lopez de Castilla, Angela R Branche, Pauline K Park, Aneesh K Mehta, William R Short, Susan L F McLellan, Susan Kline, Nicole M Iovine, Hana M El Sahly, Sarah B Doernberg, Myoung-Don Oh, Nikhil Huprikar, Elizabeth Hohmann, Colleen F Kelley, Mark Holodniy, Eu Suk Kim, Daniel A Sweeney, Robert W Finberg, Kevin A Grimes, Ryan C Maves, Emily R Ko, John J Engemann, Barbara S Taylor, Philip O Ponce, LuAnn Larson, Dante Paolo Melendez, Allan M Seibert, Nadine G Rouphael, Joslyn Strebe, Jesse L Clark, Kathleen G Julian, Alfredo Ponce de Leon, Anabela Cardoso, Stephanie de Bono, Robert L Atmar, Anuradha Ganesan, Jennifer L Ferreira, Michelle Green, Mat Makowski, Tyler Bonnett, Tatiana Beresnev, Varduhi Ghazaryan, Walla Dempsey, Seema U Nayak, Lori E Dodd, John H Beigel, Andre C Kalil
",,2022-05-23,,,,,,Publication,,2023-07-20,,,,,,,,,,"Wolfe, C. R., K. M. Tomashek, T. F. Patterson, C. A. Gomez, V. C. Marconi, M. K. Jain, O. O. Yang, C. I. Paules, G. M. R. Palacios, R. Grossberg, M. S. Harkins, R. A. Mularski, N. Erdmann, U. Sandkovsky, E. Almasri, J. R. Pineda, A. W. Dretler, D. L. de Castilla, A. R. Branche, P. K. Park, A. K. Mehta, W. R. Short, S. L. F. McLellan, S. Kline, N. M. Iovine, H. M. El Sahly, S. B. Doernberg, M. D. Oh, N. Huprikar, E. Hohmann, C. F. Kelley, M. Holodniy, E. S. Kim, D. A. Sweeney, R. W. Finberg, K. A. Grimes, R. C. Maves, E. R. Ko, J. J. Engemann, B. S. Taylor, P. O. Ponce, L. Larson, D. P. Melendez, A. M. Seibert, N. G. Rouphael, J. Strebe, J. L. Clark, K. G. Julian, A. P. de Leon, A. Cardoso, S. de Bono, R. L. Atmar, A. Ganesan, J. L. Ferreira, M. Green, M. Makowski, T. Bonnett, T. Beresnev, V. Ghazaryan, W. Dempsey, S. U. Nayak, L. E. Dodd, J. H. Beigel, and A. C. Kalil. 2022. ""Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial."" Lancet Respir Med. doi: 10.1016/s2213-2600(22)00088-1.","Free online on Pub Med Central."," Background: Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19.
Methods: In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168.
Findings: Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012).
Interpretation: In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered.
Funding: National Institute of Allergy and Infectious Diseases.
Copyright © 2022 Elsevier Ltd. All rights reserved.
",https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126560/,,,,,,,,,,,,,,,,,,,,,,,,,,,https://pubmed.ncbi.nlm.nih.gov/35617986/,,,,"2019-nCoV,Clinical Trial,COVID-19,R-Res&Pub,Research,Treatment and Care,Trial",,Publication,Discover,1,0
1683,https://repository.netecweb.org/items/show/1683,"Prepared to Act: Lessons Learned by the Special Pathogens Research Network, Based on Collaborations with the NIAID-Led Adaptive COVID-19 Treatment Trial","Emergency Management","The need for well-controlled clinical trials is fundamental to advancing medicine. Care should be taken to maintain high standards in trial design and conduct even during emergency medical events such as an infectious disease outbreak. In 2020, SARS-CoV-2 emerged and rapidly impacted populations around the globe.","Corri B Levine, Sami Vasistha, Caroline Croyle Persson, LuAnn R Larson, Christopher J Kratochvil, Aneesh K Mehta, Lindsay J Hicks, Abigail E Lowe, Mark G Kortepeter, Lauren M Sauer",,,2022-05-31,,,,,,Publication,,2023-07-20,,,,,,,,,,"Levine, C. B., S. Vasistha, C. C. Persson, L. R. Larson, C. J. Kratochvil, A. K. Mehta, L. J. Hicks, A. E. Lowe, M. G. Kortepeter, and L. M. Sauer. 2022. ""Prepared to Act: Lessons Learned by the Special Pathogens Research Network, Based on Collaborations with the NIAID-Led Adaptive COVID-19 Treatment Trial."" Health Secur 20 (S1):S20-s30. doi: 10.1089/hs.2021.0178.
","Open Access on journal site","The need for well-controlled clinical trials is fundamental to advancing medicine. Care should be taken to maintain high standards in trial design and conduct even during emergency medical events such as an infectious disease outbreak. In 2020, SARS-CoV-2 emerged and rapidly impacted populations around the globe. The need for effective therapeutics was immediately evident, prompting the National Institutes of Health to initiate the Adaptive COVID-19 Treatment Trial. The Special Pathogens Research Network, made up of 10 Regional Emerging Special Pathogens Treatment Centers, was approached to participate in this trial and readily joined the trial on short notice. By trial closure, the Special Pathogens Research Network sites, making up 19% of all study sites, enrolled 26% of the total participants. The initial resources available and experience in running clinical trials at each treatment center varied from minimal experience and few staff to extensive experience and a large staff. Based on experiences during the first phase of this trial, the Special Pathogens Research Network members provided feedback regarding operational lessons learned and recommendations for conducting future studies during a pandemic. Communication, collaboration, information technology, regulatory processes, and access to resources were identified as important topics to address. Key stakeholders including institutions, institutional review boards, and study personnel must maintain routine communication to efficiently and effectively activate when future research needs arise. Regular and standardized training for new personnel will aid in transitions and project continuity, especially in a rapidly evolving environment. Trainings should include local just-in-time training for new staff and sponsor-designed modules to refresh current staff knowledge. We offer recommendations that can be used by institutions and sponsors to determine goals and needs when preparing to set up this type of trial for critical, short-notice needs.",https://www.liebertpub.com/doi/10.1089/hs.2021.0178,,,,,,,,,,,,,,,,,,,,,,,,,,,https://pubmed.ncbi.nlm.nih.gov/35483093/,,,,"Clinical Trial,Emergency Management,NETEC,Pandemic,R-Res&Pub,Research,Special Pathogens,Trial",,Publication,Discover,1,0