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Therapeutics Clinical Working Group

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Charge

Prioritize therapeutic agents for testing within an adaptive master protocol strategy that will be jointly designed by the partnership and quickly launched in networks identified by the Clinical Trial Capacity Working Group.

Objectives

Check mark indicates completion.

✓ Agent Prioritization

The working group developed a process (see image below) to prioritize clinical agents for rapid testing:

An overview of the sources used to identify agents for prioritization in the ACTIV master protocols. The clinical therapeutics fall into four categories (antivirals, immunomodulators, supportive therapies, and neutralizing antibodies). The activities of the prioritizations team is also described as refining the process and criteria, scoring the candidates, and assessing logistical needs.

Wave 1

  • Using publicly available sources, approximately 400 candidate agents were identified. Compounds already FDA-approved were the focus to allow for quick repurposing to treat patients. An agent prioritization review committee selected by the working group used an agent triage process to narrow the list to 39 therapeutic candidates. Prioritizing the most promising candidates not already in existing clinical trials was also a focus in order to maximize the number of therapeutic agents in development to ultimately find successful treatments.
  • Using a rigorous set of prioritization criteria and a scoring system developed by the working group, the 39 candidates were split into four groups (antivirals, host targeted therapies/immune modulators, and symptomatic/supportive therapies) and scored to determine prioritization for deployment in master protocols.
  • Following a final prioritization review, the most promising agents were identified to move into clinical testing.

Wave 2 and Beyond

The prioritization process was refined, tailored to each therapy class, and applied to additional therapies submitted through the an ACTIV COVID-19 Clinical & Preclinical Candidate Compound Survey. In addition, a new agent prioritization sub-team was formed to analyze neutralizing monoclonal and polyclonal antibodies; new prioritization criteria were developed specifically for these neutralizing antibody candidates.

An overview of the actual steps in the evaluation process that generates the final list of highly promising therapeutics for testing in the ACTIV master protocols. Each step acts as a gate for the next step and leads to either more detailed consideration or removal from consideration. The types of questions that need to be addressed are shown to be related to current status in human clinical trials, efficacy data in COVID-19 treatment, and other more detailed criteria (for example human delivery data or manufacturing issues). The process that ends in initiation of the therapeutic in an ACTIV master protocol is a reproducible, scientific, data-driven process.

Based on the results of the first and subsequent waves of agent prioritization, ACTIV clinical trials are now underway.

✓ Clinical and Preclinical Candidates Survey

To assist in developing and prioritizing a complete inventory of potential candidates with different approaches to preventing or mitigating COVID-19 infection, an ACTIV COVID-19 Clinical & Preclinical Candidate Compound Survey has been established in conjunction with the Preclinical Working Group. The survey is used to collect detailed information, such as preclinical and clinical data, on therapeutic candidates. Stakeholders throughout the biopharmaceutical, academic, scientific research, advocacy, and clinical practice communities are welcome to participate in the survey.

Master Protocols for Therapeutics

The working group has assessed and designed multiple master protocols for ACTIV clinical trials, as well as selected clinical trial networks for these protocols. Using master protocols allows for the standardization of primary endpoints to enable the comparison of trial data, as well as the customization of secondary endpoints appropriate for each trial. ACTIV master protocols have been designed with a portfolio approach in mind and are intended to test all classes of agents in and appropriate patient population and setting, including immunomodulators, anticoagulants, antivirals, and neutralizing monoclonal antibodies.

Four master protocols to test the agents selected through the above prioritization process were designed (ACTIV-1, -2, -3, and -4). These are described further on the ACTIV Therapeutics Page.

Members

Neil Aggarwal, M.D.
Chief, Lung Biology and Disease Branch
National Heart, Lung, and Blood Institute, NIH

Samuel Bozzette, M.D., Ph.D.
Chief Medical Officer
National Center for Advancing Translational Sciences, NIH

Jeremy Brown, M.D.
Director, Office of Emergency Care Research
National Institute of Neurological Disorders and Stroke, NIH

Tim Buchman, M.D., Ph.D.
IPA Senior Advisor, Division of Research, Innovation and Ventures (DRIVe)
Biomedical Advanced Research and Development Authority, HHS

Captain Timothy Burgess, M.D., M.P.H.
Director, Infectious Diseases Clinical Research Program
Uniformed Services University of the Health Sciences

Joan Butterton, M.D.
Associate Vice President, Clinical Research, Infectious Diseases
Merck & Co. Inc.

Sylva Collins, Ph.D.
Director, Office of Biostatistics
U.S. Food and Drug Administration

Judith Currier, M.D.
Professor of Medicine
University of California Los Angeles
Division of Infectious Diseases
Chair, AIDS Clinical Trial Group (ACTG)

Angelo DeClaro, M.D.
Division Director (Acting), Division of Hematologic Malignancies 1
Center for Drug Evaluation and Research
U.S. Food and Drug Administration

Ruxandra Draghia-Akli, M.D., Ph.D.
Global Head, Global Public Health R&D
The Janssen Pharmaceutical Companies of Johnson & Johnson

Mark Eisner, M.D., M.P.H.
Senior Vice President, Global Head of Immunology, Infectious Disease, and Ophthalmology Clinical Development
Genentech

John Farley, M.D., M.P.H.
Director, Office of Infectious Diseases
Center for Drug Evaluation and Research
U.S. Food and Drug Administration

Carl Garner, M.S., Ph.D.
Vice President, Global Regulatory Affairs
Eli Lilly and Company

David Goff, M.D., Ph.D.
Director, Division of Cardiovascular Sciences
National Heart, Lung, and Blood Institute, NIH

Keith Gottesdiener, M.D.
Retired; past President and Chief Executive Officer
Rhythm

Elizabeth Higgs M.D., M.I.A., DTM&H
Global Health Science Advisor for the Division of Clinical Research
National Institute of Allergy and Infectious Diseases, NIH

Eric Hughes, M.D., Ph.D. (Co-Chair)
Global Development Unit Head, Immunology, Hepatology & Dermatology and China Region Development Head
Novartis

Walter Koroshetz, M.D.
Director
National Institute of Neurological Disorders and Stroke, NIH

Lisa LaVange, Ph.D.
Professor and Associate Chair, Department of Biostatistics
University of North Carolina Gillings School of Global Public Health

Elliot Levy, M.D.
Senior Vice President, Global Development
Amgen

John Mellors, M.D.
Distinguished Professor of Medicine, Chief of Division of Infectious Diseases
University of Pittsburgh School of Medicine

Sandeep Menon, M.D., Ph.D.
Senior Vice President and Head of Early Clinical Development
Pfizer

Naimish Patel, M.D.
Head of Global Development, Immunology and Inflammation Therapeutic Area
Sanofi Genzyme

Amanda Peppercorn, M.D.
Senior Medical Director, Infectious Disease
GlaxoSmithKline

Mike Poole, M.D., F.A.C.P.
Therapeutic Accelerator Lead
Bill & Melinda Gates Foundation

Michael Proschan, Ph.D.
Mathematical Statistician, Biostatistics Research Branch
National Institute of Allergy and Infectious Diseases, NIH

Sarah Read, M.D. (Co-Chair)
Deputy Director, Division of AIDS
National Institute of Allergy and Infectious Diseases, NIH

Lora Reineck, M.D., M.S.
Program Director, Acute Lung Injury/Critical Care Program
Division of Lung Diseases
National Heart, Lung, and Blood Institute, NIH

Yves Rosenberg, M.D., M.P.H.
Chief, Atherothrombosis and Coronary Artery Disease Branch
National Heart, Lung, and Blood Institute, NIH

Peter Stein, M.D.
Director of Office of New Drugs
Center for Drug Evaluation and Research
U.S. Food and Drug Administration

Pamela Tenaerts, M.D., M.B.A.
Executive Director, Clinical Trial Transformation Initiative
Duke University Clinical Research Institute

Peter Wung, M.D.
Associate Vice President, Global OMD Lead, Immuno-Inflammation
Sanofi

This page last reviewed on September 9, 2020