Trials Adding Covid-19 Hospital, Out-Patient Therapies

Transmission electron micrograph of a SARS-CoV-2 virus particle, isolated from a patient. (NIAID, NIH)

22 Apr. 2021. National Institutes of Health is adding a new treatment to a clinical trial for Covid-19 patients hospitalized with severe respiratory failure. And a related trial by National Institute of Allergy and Infectious Diseases, or NIAID, in NIH is testing a multi-action synthetic antibody to treat non-hospitalized Covid-19 patients with mild to moderate symptoms.

The two studies are part of NIH’s Accelerating Covid-19 Therapeutic Interventions and Vaccines or Activ clinical trials conducted with private companies, not-for profit organizations, and international agencies. The trials use an adaptive design that allow for changing the course of the study while underway, without compromising gold-standard quality of the efficacy or safety data. Adaptive trials are governed by a single governing board and master protocol spelling out ground rules for the study, including standards and processes for assessing results, adding or closing sample groups, and adding new drugs or devices for testing.

NIH’s Activ-3 trial is testing various treatments for hospitalized Covid-19 patients with more severe symptoms. The Activ-3 Critical Care study is a separate branch of the overall trial focusing on patients with acute respiratory failure from Covid-19 infections. The trial is testing the drug Zyesami, a synthetic form of the peptide aviptadil made by NeuroRx in Radnor, Pa. Aviptadil binds to alveolar type 2 cells that make up 10 to 15 percent of cells in the lung, and are targets of SARS-CoV-2 viruses for infection.

NeuroRx, the maker of Zyesami, says the drug protects those cells and surrounding lung tissue against cytokine enzymes in the immune system that attack the virus, preserving surfactants that maintain surface tension in the lungs. The loss of surfactants, says the company, is associated with respiratory failure in Covid-19 patients.

Testing combinations and single drugs

The Activ-3 Critical Care trial is enrolling 640 patients at two sites in the U.S. — Duke University and University of Utah medical centers — admitted with respiratory failure due from Covid-19 infections. Participants are randomly assigned to receive the standard of care with Zyesami and the authorized antiviral drug remdesivir, Zyesami and a remdesivir placebo, remdesivir and a Zyesami placebo, or placebos of both Zyesami and remdesivir.

Participants are then tracked for the next 90 days, with the study team looking mainly at the number of days patients need oxygen during their recovery at home, or if they still require hospitalization, hospice care, or die. NIAID Director Anthony Fauci says in an NIH statement, “We need more treatment options to increase the chances of recovery for people who are extremely sick so they can leave the hospital more quickly, continue their recovery at home, and return to life as usual.”

As reported by Science & Enterprise, other therapies have not fared well in the Activ-3 trial. In March, the trial dropped a combination synthetic antibody therapy made by Brii Biosciences for not meeting efficacy standards. In October 2020, the trial stopped testing the synthetic antibody therapy bamlanivimab made by Eli Lilly & Co. However, bamlanivimab combined with another synthetic antibody etesevimab received emergency clearance from FDA to treat non-hospitalized Covid-19 patients.

Testing an antibody to hit multiple targets

NIH’s Activ-2 study is another adaptive clinical trial, testing in this case treatments for Covid-19 patients not needing hospitalization. The mid- and late-stage trial is adding a synthetic antibody code-named SAB-185 made by SAB Biotherapeutics Inc. in Sioux Falls, South Dakota. The company  calls SAB-185 a polyclonal antibody since it’s designed to address multiple targets and invoke a strong immune response.

As reported by Science & Enterprise in April 2020, Department of Defense funded development of SAB-185. SAB Biotherapeutics’ technology designs synthetic forms of therapeutic antibodies, which are humanized and scaled-up for production in larger quantities inside genetically engineered cattle. The company raises and houses the engineered cattle on a ranch they call their “pharm.”

The Activ-2 trial is testing SAB-185 and four other therapies among non-hospitalized people with Covid-19 infections. Each of the treatment candidates is first tested among a group of 110 participants looking mainly for safety issues, and then in a larger sample of 421 participants testing for efficacy. In the later phase, study teams are looking primarily for recovery or hospitalization in the 28 days after treatment.

More from Science & Enterprise:

• Lilly Asks FDA to Revoke Covid-19 Therapy Clearance
• Antibody Cocktail Prevents Covid-19 Disease Symptoms
• Arthritis Drug Unsuccessful for Covid-19 Hospital Patients
• Trial Shows Inhaled Covid-19 Therapy Safe
• Microbiome Therapy Shown to Cut Covid-19 Health Needs

*     *     *