Thursday, August 6, 2020
A randomized, controlled clinical trial evaluating the safety and efficacy of a treatment regimen consisting of the antiviral remdesivir plus the immunomodulator interferon beta-1a in patients with coronavirus disease 2019 (COVID-19) has begun. The study, called the Adaptive COVID-19 Treatment Trial 3 (ACTT 3), is anticipated to enroll more than 1,000 hospitalized adults with COVID-19 at as many as 100 sites in the United States and abroad. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is sponsoring the trial.
ACTT 3 is the third iteration of NIAID's Adaptive COVID-19 Treatment Trial (ACTT). ACTT began on Feb. 21 to evaluate remdesivir, an investigational broad-spectrum antiviral discovered and developed by Gilead Sciences, Inc, of Foster City, California. A preliminary analysis of ACTT data found that patients who received remdesivir had a statistically significant shorter time to recovery compared to patients who received placebo. These results were published on May 22. More detailed information about the results, including more comprehensive data, will be available in a forthcoming report.
Subcutaneous interferon beta-1a, a medication manufactured by Merck KGaA, Darmstadt, Germany, is approved in the U.S. and more than 90 other countries for the treatment of multiple sclerosis. The drug is marketed under the brand name Rebif by EMD Serono, the North American biopharmaceutical business of Merck KGaA, Darmstadt, Germany. Interferon beta-1a has the same amino acid sequence as a naturally occurring protein called interferon beta, which is part of a class of proteins called type 1 interferons. Infected cells normally produce type 1 interferons to help the immune system fight pathogens, especially viruses. Interferon beta has both antiviral and anti-inflammatory properties.
Laboratory studies suggest that the normal interferon response is suppressed in some people after infection with SARS-CoV-2, the virus that causes COVID-19. In the laboratory, type 1 interferon can inhibit SARS-CoV-2 and two closely related viruses, SARS-CoV and MERS-CoV. In addition, two small randomized controlled trials suggest that treatment with interferon beta may benefit patients with COVID-19. The combination of interferon beta-1a and remdesivir for treating COVID-19 has not been evaluated in a large, randomized controlled trial.
In accordance with standard clinical research protocols, eligible patients who provide informed consent will participate in ACTT 3. Participants must have laboratory-confirmed SARS-CoV-2 infection with evidence of lung involvement, including a need for supplemental oxygen, abnormal chest X-rays, or illness requiring mechanical ventilation. People with confirmed infection who have mild symptoms or no apparent symptoms will not be included in the study.
ACTT 3 participants are being randomly assigned in a 1-to-1 ratio to receive either subcutaneous interferon beta-1a plus remdesivir (combination therapy) or remdesivir alone. Neither the participants nor the study team will know who is receiving which treatment regimen. All participants will receive standard doses of remdesivir and either interferon beta-1a or a placebo. Those in the combination therapy group will receive interferon beta-1a as a 44-microgram subcutaneous injection every other day for a total of four doses during hospitalization. Those in the remdesivir-only group will receive a matching placebo subcutaneous injection every other day for a total of four doses during hospitalization.
Investigators will evaluate whether time to recovery is shorter in the combination therapy group relative to the remdesivir-only group. Recovery is defined as the participant being well enough for hospital discharge, meaning the participant either no longer requires supplemental oxygen or ongoing medical care in the hospital, or is no longer hospitalized (with or without some limitation on activities). Recovery is evaluated up until day 29. A key secondary goal of the study is to compare patient outcomes at day 15 using an ordinal eight-point scale ranging from fully recovered to death. The trial also will compare other secondary outcome variables between treatment groups, including mortality alone.
An independent data and safety monitoring board (DSMB) will monitor ongoing results to ensure patient well-being and safety as well as study integrity. Preliminary results are expected in the fall of 2020.
The second iteration of the Adaptive COVID-19 Treatment Trial, ACTT 2, began on May 8 to evaluate the safety and efficacy of remdesivir plus the anti-inflammatory drug baricitinib for treating hospitalized adults with COVID-19. A product licensed to Eli Lilly and Company by Incyte and marketed under the brand name Olumiant, baricitinib(link is external) is approved in the U.S. and more than 65 other countries as a treatment for adults with moderately to severely active rheumatoid arthritis. ACTT 2 closed to enrollment on June 30 after recruiting 1,034 participants at 71 U.S. and international sites.
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. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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