Federal study of COVID treatments enters a new phase
By Gina Kolata
A large federal study that found an antiviral drug, remdesivir, can hasten the recovery in hospitalized COVID-19 patients, has begun a new phase of investigation.
Now it will examine whether adding another drug, beta interferon — which mainly kills viruses but can also tame inflammation — would improve remdesivir’s effects and speed recovery even more.
So far, remdesivir, an experimental drug, has received emergency use approval from the Food and Drug Administration to treat hospitalized COVID patients. In a large clinical trial, sponsored by the National Institutes of Health, remdesivir was shown to modestly shorten recovery time, by four days, on average, but it did not reduce deaths.
The additional drug, beta interferon, has already been approved for treatment of multiple sclerosis, which takes advantage of its anti-inflammatory effect.
The U.S. trial, known as ACCT, is designed to move quickly. Known as an adaptive trial, it is a race between treatments. It tests one treatment against another and when results are in, the drug that won that phase becomes the control drug for the next phase, in which it is tested against a different drug.
The new phase is the study’s third. A total of 1,000 patients will receive either remdesivir and a placebo or remdesivir and beta interferon.
Interferon is given as an injection. Remdesivir, made by Gilead Sciences, is given as an intravenous infusion.
A team of researchers held multiple group conference calls trying to select the new test drug for Phase 3, Dr. Peter Chin-Hong, an infectious disease expert at the University of California in San Francisco, said.
Their first suggestion was to try adding an experimental drug made by Merck known as EIDD-2801, which, like remdesivir, is an antiviral but is a pill. But they wanted something that had already been approved and available for other diseases. They hoped that by showing that the new drug was effective, and had already been approved for other illnesses, that doctors could immediately give it to COVID patients.
The group also considered dexamethasone, a common steroid that seems to be effective in reducing the death rate in severely ill patients. The drug, which suppresses inflammation, might be even better when added to remdesivir, the researchers reasoned.
But they worried. Dexamethasone is inexpensive and easily available. With widespread publicity over its apparent effectiveness, many patients would balk at joining a study in which they might get a placebo.
Then the group weighed using beta interferon, which had several things going for it. It is on the market as a treatment for multiple sclerosis, because of its weak anti-inflammatory properties. It kills the new coronavirus in laboratory studies and it wipes out severe acute respiratory syndrome and Middle East respiratory syndrome, which also are coronaviruses.
And, most impressive, Chin-Hong said, the drug was tested twice in COVID patients, with promising results. One test was in England, where beta interferon or a placebo was provided to 101 hospitalized patients. They inhaled it in a nebulizer, a device like the ones used to deliver asthma medications.
The study, although small, found that those who had received the drug recovered better than those who had received a placebo.
The other study, in Hong Kong, involved 127 patients who received beta interferon along with two antiviral drugs. The patients were hospitalized but many were not severely ill. The drug cocktail was superior to placebo in speeding recovery.
But the U.S. trial will be the only large rigorous trial to test beta interferon in COVID patients.
The first phase involving remdesivir began Feb. 21, testing the experimental drug against a placebo. That phase closed April 19 after 1,000 patients had been enrolled. The National Institute of Allergy and Infectious Diseases, which is sponsoring the study, announced preliminary results April 27.
The next phase began May 8, testing remdesivir and a placebo against remdesivir and baricitinib, an arthritis drug that quells inflammation. Researchers hoped that the addition of the arthritis drug would improve patients’ outcomes by stemming an overreaction of the immune system to the virus, a so-called cytokine storm, which can occur in severely ill patients and can be lethal. After 1,000 patients were enrolled and followed, that part of the study was closed.
Results of Phase 2 are still being evaluated. Chin-Hong said that he and others were fairly certain that if adding the arthritis drug, baricitinib, were found to have helped at all, the effect would not have been huge. If the drug had demonstrated an impressive effect, the study’s data safety and monitoring board, which oversees the trial, would have halted it and given every patient remdesivir and baricitinib. That combination would then have been the control drugs for Phase 3 of the study.
That did not happen.
Rather than wait while the data with baricitinib could be fully evaluated, the study has moved on to its next phase, testing remdesivir and placebo against remdesivir and beta interferon.
Enrollment began this month.
At the University of California in San Francisco and San Francisco General, nine patients have joined so far.
“We are approaching another today,” Chin-Hong said Monday.