A large clinical trial, evaluating the safety and efficacy of a combinatorial treatment consisting of the antiviral remdesivir plus the immunomodulator interferon beta-1a in patients with COVID-19 has begun, announced the National Institutes of Health (NIH).
The randomized, controlled clinical study, which is named Adaptive COVID-19 Treatment Trial 3 (ACTT 3), is anticipated to enroll more than 1,000 hospitalised adults with COVID-19 at as many as 100 sites in the US and abroad. ACTT 3 is the third iteration of NIH’s Adaptive COVID-19 Treatment Trial (ACTT).
ACTT began in February to evaluate remdesivir, as an investigational broad-spectrum antiviral in COVID-19 patients. 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.
Recently, two small randomised controlled trials had suggested that treatment with interferon beta may benefit patients with COVID-19. However, the combination of interferon beta-1a and remdesivir for treating COVID-19 has not been evaluated in a large, randomised controlled trial.
Subcutaneous interferon beta-1a (Rebif ) is used for the treatment of multiple sclerosis. 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. It has both antiviral and anti-inflammatory properties.
Laboratory studies have shown 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 could inhibit SARS-CoV-2 and two closely related viruses, SARS-CoV and MERS-CoV, stated the researchers.
Participants with 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 are involved in the trial. 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 hospitalisation. Those in the remdesivir-only group will receive a matching placebo subcutaneous injection every other day for a total of four doses during hospitalisation.
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 hospitalised. 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, according to NIH.