The National Institutes of Health (NIH) in the USA are to conduct a large-scale clinical trial to evaluate a new fully-human polyclonal antibody therapy targeted at severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of coronavirus disease 2019 (COVID-19).
Non-hospitalized people with mild or moderate cases of COVID-19 are to be enrolled at sites around the world, for a test trial called ACTIV-2, which is a part of NIH’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program.
On April 17, 2020, the National Institutes of Health (NIH) announced the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership to develop a coordinated research strategy for prioritizing and speeding development of the most promising treatments and vaccines.”
ACTIV-2, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, is designed to evaluate a therapeutic candidate called SAB-185, in a small group of volunteers. This master protocol will further continue to test if the antibody appears safe and effective in a larger group. The trial for ACTIVE-2 began on August 4, 2020. It has since added several therapeutics for testing.
The SAB-185, developed by SAB Biotherapeutics, Inc. (Sioux Falls, South Dakota), is a fully human polyclonal antibody therapeutic candidate for COVID-19. It has completed enrollment of Phase 1 and Phase 1b clinical studies, where SAB-185 neutralized the live SARS-CoV-2 at titers higher than convalescent plasma.
This therapeutic candidate, SAB-185, was developed from SAB’s platform, which uses genetically engineered cattle. These produce fully human antibodies through a scalable and reliable process.
ACTIV-2 is designed for evaluating ‘multiple investigational agents’ in adults with mild-to-moderate COVID-19 who are non-hospitalized. The news release revealed the other therapeutics currently being evaluated in ACTIV-2, (in addition to SAB-185). These include:
- A regimen of two experimental antibodies, BRII-196 and BRII-198, developed by Brii Biosciences based in Durham, North Carolina and Beijing, China
- SNG001, 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.
The SAB-185 is administered intravenously, with the dose depending on the patient’s weight in kilograms (kg). Both high and low doses of SAB-185 are tested in this trial.
The Phase 2 evaluation will enroll 110 participants (each for the therapeutic candidate and placebo) with mild or moderate COVID-19 who are at risk of disease progression. In a blinded trial, where when participants enroll in ACTIV-2, they will be randomly assigned to receive either SAB-185, another therapeutic that is currently being evaluated (as mentioned above), or a placebo. Participants will attend a series of clinic or at-home visits by clinicians and will be followed for a total of 72 weeks.
The news reported that an independent Data and Safety Monitoring Board (DSMB) overseeing the trial will review the data collected in 28 days. If they observe that the therapeutic candidate reduces the duration of COVID-19 symptoms and eliminates the virus from the body, the therapy will be inferred as safe.
With promising results from this trial (and no safety concerns), Phase 2 will transition to Phase 3, where an additional number of volunteers will be enrolled: 421 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.”
Even as the COVID-19 pandemic rages on, exacting an enormous toll on global public health and the economy, effective therapeutics are yet to come into the market for clinical use. Many of the successful candidates are under trial at various stages of evaluation.