NIH Begins Clinical Trial of Antiviral Remdesivir Plus Immunomodulator Interferon Beta-1a in COVID-19 Patients

The National Institutes of Health (NIH Bethesda, MA, USA) has begun 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 COVID-19 patients.

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 US and abroad. ACTT 3 is the third iteration of NIAID’s Adaptive COVID-19 Treatment Trial (ACTT). ACTT began in February to evaluate remdesivir, an investigational broad-spectrum antiviral discovered and developed by Gilead Sciences (Foster City, CA, USA; www.gilead.com). 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.

Subcutaneous interferon beta-1a, a medication manufactured by Merck KGaA (Darmstadt, Germany; www.merckgroup.com), is approved in the US 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.

ACTT 3 participants will 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. They will be 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.

The trial will evaluate whether time to recovery is shorter in the combination therapy group relative to the remdesivir-only group. 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.

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The National Institutes of Health (NIH)
Gilead Sciences
Merck KGaA