The National Institutes of Health (NIH) announced today the launch of the third iteration of the National Institute of Allergy and Infectious Diseases’ (NIAID) Adaptive COVID-19 Treatment Trial (ACTT) pairing remdesivir and interferon beta-1a.
The randomized, controlled clinical trial, which will evaluate the safety and efficacy of the combination treatment regimen in patients with COVID-19, is called the Adaptive COVID-19 Treatment Trial 3 (ACTT 3). NIAID, the trial’s sponsor, plans to enroll more than 1,000 hospitalized adults with COVID-19 at as many as 100 sites in the U.S. and abroad.
ACTT 3 is the third iteration of ACTT program, which first began Feb. 21 to evaluate remdesivir, an investigational broad-spectrum antiviral from Gilead Sciences. A preliminary analysis of ACTT data published in May found that patients who received remdesivir had a statistically significant shorter time to recovery compared to patients who received placebo. Subcutaneous interferon beta-1a (brand name Rebif), is a medication produced by Merck KGaA, and is approved in the U.S. and more than 90 other countries for the treatment of multiple sclerosis (MS). 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.
Laboratory studies suggest that the normal interferon response is suppressed in some people after infection with SARS-CoV-2. Laboratory tests have also shown that type 1 interferon can inhibit SARS-CoV-2 and the related viruses SARS-CoV and MERS-CoV. Two small, randomized controlled trials have suggested interferon beta may benefit patients with COVID-19, but the combination of interferon beta-1a and remdesivir for treating COVID-19 has not been evaluated in a large, randomized controlled trial.
Patients selected for the trial must have a 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 the combination of subcutaneous interferon beta-1a plus remdesivir, or remdesivir alone. In this double-blinded study, 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.
The study will seek to determine whether time to recovery is shorter in the combination therapy group relative to the remdesivir-only group, with recovery defined as the patient 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 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.
