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

ACTIV Fast-Track Areas

ACTIV Governance

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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.
  • 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.
  • 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

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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

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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

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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

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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

See the ACTIV Organization Chart (PDF, 207 KB).

Government Organizations 

  • Biomedical Advanced Research and Development Authority 

  • Centers for Disease Control and Prevention 

  • Department of Defense 

  • Department of Veterans Affairs 

  • European Medicines Agency 

  • National Institutes of Health 

  • Operation Warp Speed 

  • U.S. Food and Drug Administration 

Industry 

  • AbbVie, Inc. 

  • Amgen 

  • AstraZeneca 

  • Bristol Myers Squibb 

  • Eisai 

  • Eli Lilly and Company 

  • Evotec 

  • Gilead 

  • GlaxoSmithKline 

  • Johnson & Johnson 

  • Merck & Co., Inc. 

  • Moderna, Inc. 

  • Novartis 

  • Novavax 

  • Pfizer 

  • Rhythm Therapeutics 

  • Roche/Genentech 

  • Sanofi 

  • Takeda 

  • Vir Biotechnology 

Nonprofit 

  • Bill & Melinda Gates Foundation 

  • Fred Hutchinson Cancer Research Center 

  • Foundation for the National Institutes of Health 

  • 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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