Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) is a public-private partnership to coordinate research and speed the development of the most promising COVID-19 treatments and vaccines.
Coordinated by the Foundation for the National Institutes of Health, ACTIV brings together NIH and its sibling agencies in the Department of Health and Human Services—including the Biomedical Advanced Research and Development Authority, Centers for Disease Control and Prevention, and the U.S. Food and Drug Administration—as well as other government agencies both at home and abroad, including the Department of Defense and Department of Veterans Affairs, Operation Warp Speed, and the European Medicines Agency. ACTIV also includes representatives from academia, philanthropic organizations, and numerous biopharmaceutical companies.
Read more about the history of ACTIV and its partners and goals.
ACTIV Protocols
The ACTIV public-private partnership has designed five adaptive master protocols for ACTIV clinical trials to test COVID-19 therapies. Master protocols allow coordinated and efficient evaluation of multiple investigational agents, but within the same clinical trial structure, across multiple study sites. Adaptive protocols swiftly weed out experimental drugs that do not demonstrate effectiveness and identify those that do. Adaptive master protocols provide a flexible framework to rapidly identify drugs that work, and rapidly move additional experimental agents into the trial.
The ACTIV master protocols are listed below. As studies of specific compounds are launched, we will list those studies under each protocol.
The ACTIV-1 master protocol will test promising immune modulator compounds, a class of drugs that help minimize the deleterious effects of an overactive immune response to SARS-CoV-2 infection. This Phase 3 trial is enrolling hospitalized adults with moderate to severe COVID-19 disease. It is evaluating the safety and efficacy of at least three immune modulators when given as an add-on therapy to remdesivir, an antiviral approved for treatment of COVID-19, and the standard of care in use at local clinics. The different treatments will be assessed with respect to illness severity, recovery speed, mortality, and hospital resource utilization.
- Remicade® (infliximab) / Phase 3
A monoclonal antibody donated by Janssen Biotech, Inc., that inhibits tumor necrosis factor, a pro-inflammatory cytokine hypothesized to drive the excess inflammatory response some experience during advanced stages of COVID-19. Remicade received FDA approval in 1998 to treat several chronic auto-immune inflammatory diseases. - Orencia® (abatacept) / Phase 3
Orencia, a selective T-cell co-stimulation immunomodulator donated by Bristol Myers Squibb, consists of the extracellular domain of human cytotoxic T cell-associated antigen 4 fused to a modified immunoglobulin tail and works by preventing the full activation of T cells, which also helps inhibit the downstream inflammatory cascade. - Cenicriviroc (CVC) / Phase 3
CVC, donated by AbbVie Inc., blocks CCR2 and CCR5 chemokine receptors involved in the inflammatory and fibrogenic pathways of certain diseases potentially reduced with immunomodulation therapy.
ACTIV-2 is designed as a Phase 2 trial that can expand seamlessly to Phase 3. The trial is enrolling adults with COVID-19 who are not hospitalized and aims to evaluate safety, to understand if the investigational treatment can reduce the duration of symptoms, and to test if the treatment can increase the proportion of participants with undetectable virus. It will perform testing using nasopharyngeal swabs at specific time points. ACTIV-2 is testing multiple therapies, beginning with a monoclonal antibody but including other types of therapeutics.
- LY-CoV555 / Phase2/3
An investigational antibody developed by Eli Lilly and Co. in partnership with AbCellera Biologics. AbCellera collaborated with NIAID’s Vaccine Research Center to identify and isolate the antibody from a blood sample from a person who recovered from COVID-19.
The ACTIV-3 master protocol is designed as a Phase 3 trial with two stages of testing, allowing for quick analysis of compounds for effectiveness in Stage 1 and then a seamless progression to Stage 2 to validate the compound for broader use in patients. The trial is enrolling hospitalized adults with COVID-19 and primarily aims to evaluate safety and to understand if the investigational treatment can reduce time to recovery and to understand a treatment’s effect on extrapulmonary complications and respiratory dysfunction. ACTIV-3 is testing multiple therapies, beginning with a monoclonal antibody but including other types of therapeutics.
- LY-CoV555 / Phase 3 (This sub-study has closed.)
An investigational antibody developed by Eli Lilly and Co. in partnership with AbCellera Biologics. AbCellera collaborated with NIAID’s Vaccine Research Center to identify and isolate the antibody from a blood sample from a person who recovered from COVID-19. This study closed because the Data Safety Monitoring Board determined low likelihood that the intervention would be of clinical value in this hospitalized patient population.
The ACTIV-4 master protocol is evaluating the safety and effectiveness of varying types of blood thinners to treat adults diagnosed with COVID-19. Currently there are three adaptive platform clinical trials within ACTIV-4 that aim to prevent, treat, and address COVID-19-associated coagulopathy (CAC), or clotting, as well as help understand the effects of CAC across three patient populations: inpatient, outpatient, and convalescent. The trial infrastructure is also poised to rapidly test promising new agents. The adaptive nature of the platform will allow a seamless transition to studies that will test multi-regimen anticoagulation approaches.
- ACTIV-4 Outpatient Trial: Investigates whether anticoagulants or antithrombotic therapy can reduce life-threatening cardiovascular or pulmonary complications in newly diagnosed COVID-19 patients who do not require hospital admission. Participants are assigned to take either a placebo, aspirin, or a low or therapeutic dose the blood thinner apixaban.
- Apixaban / Phase 3
Direct oral anticoagulant donated by Bristol Myers Squibb/Pfizer - Aspirin / Phase 3
Anti-platelet agent donated by Bristol Myers Squibb/Pfizer
- Apixaban / Phase 3
- ACTIV-4 Inpatient Trial: Investigates an approach aimed at preventing clotting events and improving outcomes in hospitalized COVID-19 patients. It is evaluating the safety and effectiveness of using varying doses of heparin, a blood thinner, to prevent or reduce the formation of blood clots.
- Unfractionated (UF) and Low Molecular Weight (LMW) heparin / Phase 3
Agents used for in-hospital anticoagulation
- Unfractionated (UF) and Low Molecular Weight (LMW) heparin / Phase 3
- ACTIV-4 Convalescent Trial: Investigates the effectiveness and safety of anticoagulants and/or antiplatelets administered to patients who have been discharged from the hospital or are convalescing in reducing thrombotic complications such as heart attack, stroke, blood clots in major veins and arteries, deep vein and pulmonary thrombosis, and death. Researchers will assess if patients develop these complications within 45 days of being hospitalized for moderate and severe COVID-19.
The ACTIV-5 master protocol is designed to conduct a series of randomized, double-blind, placebo-controlled Phase 2 trials using common assessments and endpoints. Trials using this protocol are enrolling hospitalized adults with COVID-19 to evaluate whether certain approved therapies or investigational drugs in late-stage clinical development show promise against COVID-19. Compounds that do not demonstrate efficacy based in interim evaluations will be dropped, while those that demonstrate efficacy will move forward to Phase 3 trials.
- Risankizumab / Phase 2
A monoclonal antibody developed by Boehringer Ingelheim and AbbVie and approved in the U.S. for the treatment of severe plaque psoriasis. The therapeutic is given in conjunction with the antiviral drug remdesivir and is compared with placebo and remdesivir. - Lenzilumab / Phase 2
An investigational monoclonal antibody developed by Humanigen. The therapeutic is given in conjunction with the antiviral drug remdesivir and is compared with placebo and remdesivir.
ACTIV Fast-Track Areas
Through ACTIV, NIH is focusing on four fast-track areas, each led by a working group of senior scientists representing government, industry, nonprofit, and academic organizations.
Preclinical Working Group

Goal:
Develop a collaborative, streamlined forum to identify preclinical treatments.
Summary:
- Establish a centralized process and repository for harmonizing and sharing methods and evaluating animal models
- Extend access to high-throughput screening facilities, especially in biosafety level 3 (BSL-3) labs
- Increase access to validated animal models
- Enhance comparison of approaches to identify informative assays
Therapeutics Clinical Working Group

Goal:
Accelerate clinical testing of the most promising vaccines and treatments.
Summary:
- Establish a steering committee with relevant expertise to set criteria for and rank potential candidates submitted by industry partners for testing
- Develop a complete inventory of potential candidates with different mechanisms of action and acceptable safety profiles
- Design, launch, and openly share master protocols with agreed-upon endpoints, sampling, and analysis for evaluating candidates
- Use a single control arm to enhance trial efficiency
Clinical Trial Capacity Working Group

Goal:
Improve clinical trial capacity and effectiveness.
Summary:
- Specialize in different populations and disease stages
- Leverage infrastructure and expertise from across NIH and non-NIH networks and clinical research organizations
- Establish a coordinated mechanism across networks to expedite trials
- Track incidence across sites and project future capacity
Vaccines Working Group

Goal:
Accelerate the evaluation of vaccine candidates to enable rapid authorization or approval.
Summary:
- Harmonize studies to enable analysis of protection across vaccines
- Create a collaborative framework to share insights into natural immunity and vaccine candidate-induced immune response
ACTIV Governance and Leadership
Government Organizations
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Biomedical Advanced Research and Development Authority
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Centers for Disease Control and Prevention
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Department of Defense
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Department of Veterans Affairs
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European Medicines Agency
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National Institutes of Health
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Operation Warp Speed
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U.S. Food and Drug Administration
Industry
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AbbVie, Inc.
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Amgen
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AstraZeneca
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Bristol Myers Squibb
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Eisai
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Eli Lilly and Company
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Evotec
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Gilead
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GlaxoSmithKline
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Johnson & Johnson
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Merck & Co., Inc.
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Moderna, Inc.
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Novartis
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Novavax
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Pfizer
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Rhythm Therapeutics
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Roche/Genentech
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Sanofi
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Takeda
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Vir Biotechnology
Nonprofit
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Bill & Melinda Gates Foundation
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Fred Hutchinson Cancer Research Center
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Foundation for the National Institutes of Health
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RTI International
Francis Collins, M.D., Ph.D. (Co-Chair)
NIH
Paul Stoffels, M.D. (Co-Chair)
Johnson & Johnson
Gary Disbrow, Ph.D.
Biomedical Advanced Research and Development Authority
Mikael Dolsten, M.D., Ph.D.
Pfizer
Anthony Fauci, M.D.
National Institute of Allergy and Infectious Diseases
Gary Gibbons, M.D.
National Heart, Lung, and Blood Institute
Peter Marks, M.D., Ph.D.
U.S. Food and Drug Administration
William Pao, M.D., Ph.D.
Roche
Andrew Plump, M.D., Ph.D.
Takeda Pharmaceutical Co. Ltd.
Janet Woodcock, M.D.
Operation Warp Speed
Peter Adams, Ph.D.
Biomedical Advanced Research and Development Authority
Annaliesa Anderson, Ph.D., FAAM
Pfizer
James Anderson, M.D., Ph.D.
NIH Office of the Director
Ralph Baric, Ph.D.
University of North Carolina, Chapel Hill
Kara Carter, Ph.D.
Evotec
Marc Charette, Ph.D.
National Heart, Lung, and Blood Institute
Tomas Cihlar, Ph.D.
Gilead Sciences, Inc.
Christine Colvis, Ph.D. (Co-Chair)
National Center for Advancing Translational Sciences
Michael Diamond, M.D., Ph.D.
Washington University School of Medicine in St. Louis
Ken Duncan, Ph.D.
Bill & Melinda Gates Foundation
Prabhavathi Fernandes, Ph.D.
Global Antibiotic Research and Development Partnership
National Biodefense Science Board
Joshua Fessel, M.D., Ph.D.
National Heart, Lung, and Blood Institute
Clint Florence, Ph.D.
National Institute of Allergy and Infectious Diseases
Greg Gatto, Ph.D.
RTI International
Jay Grobler, Ph.D.
Merck & Co., Inc.
Nancy Haigwood, Ph.D.
Oregon Health & Science University
Judith Hewitt, Ph.D.
National Institute of Allergy and Infectious Diseases
Sheri Hild, Ph.D.
NIH Office of Research Infrastructure Programs
Samantha Jonson, M.P.S.
National Center for Advancing Translational Sciences
Isis Kanevsky, Ph.D.
Pfizer
Cat Lutz, Ph.D.
The Jackson Laboratory
Stephen Mason, Ph.D.
Pfizer
Frank Nestle, M.D.
Sanofi
Elizabeth Ottinger, Ph.D.
National Center for Advancing Translational Sciences
David Payne, Ph.D.
GlaxoSmithKline
Louise Pitt, Ph.D.
U.S. Army Medical Research Institute of Infectious Diseases
Antonello (Tony) Punturieri, M.D., Ph.D.
National Heart, Lung, and Blood Institute
Srinivas Rao, D.V.M., Ph.D.
Sanofi
Jay Rappaport, Ph.D.
Tulane University National Primate Research Center
Frank Stegmeier, Ph.D.
KSQ Therapeutics
John Young, Ph.D. (Co-Chair)
Roche
Roland Zahn, Ph.D.
Janssen Vaccines and Prevention
Neil Aggarwal, M.D.
National Heart, Lung, and Blood Institute
Samuel Bozzette, M.D., Ph.D.
National Center for Advancing Translational Sciences
Jeremy Brown, M.D.
National Institute of Neurological Disorders and Stroke
Tim Buchman, M.D., Ph.D.
Biomedical Advanced Research and Development Authority
Captain Timothy Burgess, M.D., M.P.H.
Uniformed Services University of the Health Sciences
Joan Butterton, M.D.
Merck & Co., Inc.
Sylva Collins, Ph.D.
U.S. Food and Drug Administration
Judith Currier, M.D.
University of California, Los Angeles
AIDS Clinical Trial Group
Angelo DeClaro, M.D.
U.S. Food and Drug Administration
Ruxandra Draghia-Akli, M.D., Ph.D.
Janssen Pharmaceutical Companies of Johnson & Johnson
Mark Eisner, M.D., M.P.H.
Genentech
John Farley, M.D., M.P.H.
U.S. Food and Drug Administration
Carl Garner, M.S., Ph.D.
Eli Lilly and Company
David Goff, M.D., Ph.D.
National Heart, Lung, and Blood Institute
Keith Gottesdiener, M.D.
Rhythm Pharmaceuticals
Elizabeth Higgs, M.D., M.I.A., DTM&H
National Institute of Allergy and Infectious Diseases
Eric Hughes, M.D., Ph.D. (Co-Chair)
Novartis
Walter Koroshetz, M.D.
National Institute of Neurological Disorders and Stroke
Lisa LaVange, Ph.D.
University of North Carolina Gillings School of Global Public Health
Elliot Levy, M.D.
Amgen
John Mellors, M.D.
University of Pittsburgh School of Medicine
Sandeep Menon, M.D., Ph.D.
Pfizer
Naimish Patel, M.D.
Sanofi
Amanda Peppercorn, M.D.
GlaxoSmithKline
Mike Poole, M.D., FACP
Bill & Melinda Gates Foundation
Michael Proschan, Ph.D.
National Institute of Allergy and Infectious Diseases
Sarah Read, M.D. (Co-Chair)
National Institute of Allergy and Infectious Diseases
Lora Reineck, M.D., M.S.
National Heart, Lung, and Blood Institute
Yves Rosenberg, M.D., M.P.H.
National Heart, Lung, and Blood Institute
Peter Stein, M.D.
U.S. Food and Drug Administration
Pamela Tenaerts, M.D., M.B.A.
Duke University Clinical Research Institute
Peter Wung, M.D.
Sanofi
Lionel Bascles, Ph.D.
Sanofi
Myron Cohen, M.D.
University of North Carolina, Chapel Hill
Lawrence Corey, M.D.
Fred Hutchinson Cancer Research Center
Victoria Davey, Ph.D., M.P.H.
U.S. Department of Veterans Affairs
Elizabeth Desrosiers, M.S., PMP (Co-Chair)
Merck & Co., Inc.
James Dickens
National Center for Advancing Translational Sciences
Jim Doroshow, M.D.
National Cancer Institute
Carlos Garner, Ph.D.
Eli Lilly and Company
David Goff, M.D., Ph.D.
National Heart, Lung, and Blood Institute
Penny Heaton, Ph.D.
Bill & Melinda Gates Medical Research Institute
Michael Kurilla, M.D., Ph.D. (Co-Chair)
National Center for Advancing Translational Sciences
George Mensah, M.D.
National Heart, Lung, and Blood Institute
Seema Nayak, M.D.
National Institute of Allergy and Infectious Diseases
Manizhe Payton, M.P.H.
National Institute of Allergy and Infectious Diseases
Laura Resnansky, B.S.N.
Genentech
Christine Sizemore, Ph.D.
Fogarty International Center, NIH
Badhri Srinivasan, A.B.D., M.S.
Novartis
Peter Stein, M.D.
U.S. Food and Drug Administration
Therese Takas
AstraZeneca
Mike Vincent, M.D., Ph.D.
Pfizer
Gail Weinmann, M.D.
National Heart, Lung, and Blood Institute
Paula Annunziato, M.D.
Merck & Co., Inc.
Ann Arvin, M.D.
Stanford University School of Medicine
Beth Bell, M.D.
University of Washington
Susan Buchbinder, M.D.
University of California, San Francisco
San Francisco Department of Public Health
Marco Cavaleri, Ph.D.
European Medicines Agency
Lawrence Corey, M.D.
Fred Hutchinson Cancer Research Center
Mark Davis, Ph.D.
Stanford Institute for Immunology, Transplantation and Infection
Stanford University School of Medicine
Emilio Emini, Ph.D.
Bill & Melinda Gates Foundation
Gregory Glenn, M.D.
Novavax, Inc.
Emmanuel Hanon, Ph.D.
GlaxoSmithKline
Barton Haynes, M.D.
Duke University
Peter Hotez, M.D., Ph.D.
Baylor College of Medicine
Texas Children’s Hospital
Kathrin Jansen, Ph.D. (Co-Chair)
Pfizer
Antonio Lanzavecchia, M.D.
Vir Biotechnology, Inc.
Institute for Research in Biomedicine
Douglas Lowy, M.D. (Co-Chair)
National Cancer Institute
Peter Marks, M.D., Ph.D.
U.S. Food and Drug Administration
John Mascola, M.D.
National Institute of Allergy and Infectious Diseases
Nancy Messonnier, M.D.
Centers for Disease Control and Prevention
Nelson Michael, M.D., Ph.D.
Walter Reed Army Institute of Research, U.S. Army Medical Research and Development Command
Paul Offit, M.D.
University of Pennsylvania
Children’s Hospital of Philadelphia
Hanneke Schuitemaker, Ph.D.
Johnson & Johnson
University of Amsterdam
Jonathan Seals, Ph.D.
Biomedical Advanced Research and Development Authority
Jim Tartaglia, Ph.D.
Sanofi Pasteur
Tonya Villafana, M.P.H., Ph.D.
AstraZeneca
Tal Zaks, M.D., Ph.D.
Moderna, Inc.
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