The National Health Institute (NIH) foundation set up the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program to direct federal research dollars and resources to COVID-19 clinical trials. The public-private partnership program, critiqued by TrialSite for lack of diversity both in terms of representation from the real-world clinic as well as ethnic minorities at leadership and in the various programs, was formed to create a coordinated research strategy that prioritizes and accelerates the development of promising COVID-19 treatments and vaccines. The ACTIV-2 program represents an adaptive trial designed to test investigational agents in non-hospitalized adult volunteers experiencing mild to moderate COVID-19 symptoms. Sponsored by the National Institutes of Allergy and Infectious Diseases (NIAID)—led by Dr. Anthony Fauci and part of the NIH—the AIDS Clinical Trials Group (ACTG) leads the investigation. ACTIV-2 recently added sub-studies to test four interventions for safety and efficacy, including SNG001, inhalable beta interferon delivered by nebulizer (Synairgen); AstraZeneca’s AZD7442, a long-acting monoclonal antibody study as both infusion and intramuscular injection; Camostat mesilate, an orally administered serine protease inhibitor that may block SARS-CoV-2 from entering cells (Sagent Pharmaceuticals). Apparently, the first volunteer enrollments in the SNG001 sub-study occurred on Feb 10. With the other agents under study expected to commence enrollment soon, the TrialSite ponders why isn’t NIAID including a study on ivermectin as well? The latest meta-analysis developed by Dr. Andrew Hill, affiliated with University of Liverpool, approaches 3,500 patients and significant benefits associated with that generic drug.
An Adaptive Platform
NIAID designed ACTIV-2 as an adaptive trial meaning that if a particular investigational agent shows promise by demonstrating safety and reducing COVID-19 symptoms through 28 days following administration, the ACTIV-2 trial can expand seamlessly from Phase 2 to a Phase 3 study to gather additional critical data from a larger pool of volunteers without delay.
Phase 2 studies in ACTIV-2 enroll up to 220 volunteers, reports the NIH press release, but the exact Phase 3 enrollment size varies based on the mode of administration of the study agent. This adaptive desired study supports the comparison of multiple interventions with a shared group of placebo recipients. Moreover, ACTIV-2 studies also investigate whether a particular investigational agent can reduce the amount of SARS-CoV-2 virus detectable in the nasopharynx.
How do Participants Qualify?
Participants in ACTIV-2 must have tested positive for COVID-19 in the outpatient setting within 10 days and started experiencing symptoms within eight days of enrolling. Note that participants eligible for the AZD7442 infusion study must have a risk factor that puts them at a higher probability of progressing to severe COVID-19. This could include one over the age of 60, a current smoker, or having one of a number of conditions such as chronic lung, kidney or liver disease, obesity, hypertension, cardiovascular disease, diabetes, current cancer or immunosuppression.
ACTIV-2 Study led to EUA for Lilly’s LY-CoV555
ACTIV-2 supported the study investigating the Eli Lilly monoclonal antibody called LY-CoV555 (bamlanivimab), which was ultimately granted Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration for treating mild to moderate COVID-19 in adults and children over 12 who are at high risk for progressing to severe COVID-19 and/or hospitalization. Note that some physicians have been critical of this particular treatment as it is relatively challenging to administer. It isn’t useful for the great majority of COVID-19 cases, which are mild cases needing rather ideally a form of antiviral. TrialSite recently reported on the ACTIV-2 study testing monoclonal antibodies from Chinese headquartered Brii Biosciences (also located in Durham, NC).
Studies Go On
It’s important to note that despite mass vaccination pushes, the NIAID continues to promote significant research as its abundantly clear the need for therapeutics that can also treat COVID-19. TrialSite reminds the audience that there are also possible repurposed drugs that show significant promise, including ivermectin, fluvoxamine and colchicine, for example. Up in Canada, Dr. Reddy’s has submitted a market authorization to Health Canada for favipiravir.
- Davey Smith, MD, University of California, San Diego (UCSD) (protocol co-chair)
- Kara W. Chew, MD, MS, University of California, Los Angeles (UCLA), (protocol co-chair)
- David Alain Wohl, MD, University of North Carolina at Chapel Hill (UNC) (protocol-vice chair)
- Eric S. Daar, MD, UCLA (protocol vice-chair)
- Judith Currier, MD, MSc, UCLA (ACTG network chair)
- Joseph Eron, MD, UNC, (ACTG network co-chair)
Call to Action: Interested in these investigational therapies—check out the ACT-2 studies.