The NIH intramural research program has shifted all non-mission-critical laboratory operations to a maintenance phase in order to promote physical distancing and diminished transmission risk of COVID-19. Effective Monday, March 23, 2020, only mission-critical functions within NIH research laboratories will be supported.

COVID-19 Therapeutics Prioritized for Testing in Clinical Trials

In the last three months, working in an unprecedented timeframe, the ACTIV public-private partnership has evaluated hundreds of available therapeutic agents with potential application for COVID-19, prioritized the most promising candidates, designed and harmonized four adaptive master protocols for ACTIV clinical trials, and selected numerous NIH-supported networks to launch these clinical trials to test prioritized therapeutic candidates.

Master protocols allow coordinated and efficient evaluation of multiple investigational agents as they become available, 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 reduce administrative burden and cost, 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, NIH will list those studies under each protocol.

ACTIV-1

Immune Modulators

Young male nurse in white scrubs standing at bedside with hand on shoulder of recovering mature male COVID-19 patient, both wearing protective masks.

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 will enroll hospitalized adults with moderate to severe COVID-19 disease. It will evaluate 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.

ACTIV-2

Outpatient Monoclonal Antibodies and Other Therapies

Doctor talking to senior female patient while being in a home visit

ACTIV-2 is designed as a Phase 2 trial that can expand seamlessly to Phase 3. The trial will enroll 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. Multiple therapies, beginning with a monoclonal antibody but including other types of therapeutics, will be tested in ACTIV-2.

Agent Trial Phase Description More Information

LY-CoV555

Phase 2/3

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.

News Release

ACTIV-3

Inpatient Monoclonal Antibodies and Other Therapies

Health visitor using digital tablet and talking to a senior man during home visit

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 will enroll 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. Multiple therapies, beginning with a monoclonal antibody but including other types of therapeutics, will be tested in ACTIV-3.

Agent Trial Phase Description More Information

LY-CoV555

Phase 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.

News Release

ACTIV-4

Antithrombotics

Happy senior woman listening as her doctor is explaining therapy details during house call visit

This master protocol will evaluate the safety and effectiveness of varying types of blood thinners to treat adults diagnosed with COVID-19. No less than three adaptive platform clinical trials will evolve under the umbrella of ACTIV-4 as data emerges. The trial infrastructure will also be 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.

The three trials within ACTIV-4 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.

This page last reviewed on August 4, 2020