A Phase 2/3 trial to evaluate a new fully-human polyclonal antibody therapeutic targeted to SARS-CoV-2, called SAB-185, has begun enrolling non-hospitalized people with mild or moderate cases of COVID-19. The trial, ACTIV-2, is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The therapeutic was developed by SAB Biotherapeutics, Inc. (Sioux Falls, South Dakota).
NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program is a public-private partnership to develop a coordinated research strategy for speeding development of the most promising treatments and vaccine candidates. ACTIV-2 is a master protocol designed for evaluating multiple investigational agents in adults with mild-to-moderate COVID-19 who are not hospitalized. Led by the NIAID-funded AIDS Clinical Trials Group (ACTG) and supported by PPD (Wilmington, North Carolina), a global contract research organization that is responsible for trial execution, the trial will enroll participants at sites around the world.
The ACTIV-2 study design allows researchers to evaluate SAB-185 in a small group of volunteers and then continue testing it in a larger group if the antibody appears safe and effective. The trial began on Aug. 4, 2020 and has since added several therapeutics for testing.
SAB-185 is a fully-human polyclonal antibody therapeutic candidate for COVID-19 that has completed enrollment of Phase 1 and Phase 1b clinical studies. In previous pre-clinical studies, SAB-185 demonstrated neutralization of live SARS-CoV-2 at titers higher than convalescent plasma. The therapeutic candidate was developed from SAB’s platform, which uses genetically engineered cattle to produce fully-human antibodies in a process designed to potentially be both scalable and reliable.SAB-185 is administered intravenously, with the dose depending on the patient’s weight in kilograms (kg). A high and a low dose of SAB-185 will be tested in this trial.
When participants enroll in ACTIV-2, they will be assigned at random to receive either SAB-185, another therapeutic currently being evaluated in ACTIV-2, or a placebo. Other therapeutics currently being evaluated in ACTIV-2 include:
- a regimen of two experimental antibodies, BRII-196 and BRII-198, developed by Brii Biosciences based in Durham, North Carolina and Beijing;
- SNG001, an inhalable beta interferon developed by Synairgen based in Southampton, United Kingdom;
- AZD7442, a long-acting monoclonal antibody combination administered by either an intravenous infusion or an intramuscular injection, developed by AstraZeneca based in Cambridge, United Kingdom
- Camostat mesilate, an orally administered serine protease inhibitor developed by Sagent Pharmaceuticals based in Schaumburg, Illinois.
In the Phase 2 evaluation, each agent tested in ACTIV-2, and the shared placebo group, will enroll 110 participants with mild or moderate COVID-19 who are at risk for disease progression. The trial is blinded, so neither participants nor investigators will know whether a participant is receiving the therapeutic or the placebo. Participants will attend a series of clinic or at-home visits by clinicians and will be followed for a total of 72 weeks.
An independent Data and Safety Monitoring Board (DSMB) overseeing the trial will review the data collected at 28 days. They will monitor data to see if the therapy is safe, reduces the duration of COVID-19 symptoms and eliminates virus from the body. If there are no serious safety concerns and the results of this Phase 2 study seem promising, the trial will transition to Phase 3. It will then enroll 421 additional volunteers to receive the SAB agent, and 421 volunteers in the placebo group. The primary objective of the Phase 3 trial is to determine if the SAB therapy prevents either hospitalization or death by 28 days after study entry.
The study team for ACTIV-2 is led by protocol chairs Kara W. Chew, M.D., of the University of California, Los Angeles (UCLA), and Davey Smith, M.D., of the University of California, San Diego. Eric S. Daar, M.D., of UCLA, and David Wohl, M.D., of the University of North Carolina at Chapel Hill (UNC), serve as protocol vice-chairs. Babafemi Taiwo, MBBS of Northwestern University is a co-investigator focused on the SAB agent. The ACTG network is led by chair Judith Currier, M.D., (UCLA) and vice-chair Joseph Eron, M.D., of UNC.
NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses.