In the battle against COVID-19, clinical trials enable researchers and clinicians to field test the weapons they hope will help end the current pandemic and prevent more from occurring. Trials to evaluate therapies for COVID-19 outpatients — those people diagnosed with cases of the disease not severe enough to require hospitalization — are now being conducted under the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-2) program. The program is part of Operation Warp Speed, the federal government’s COVID-19 treatment development effort led by the National Institutes of Health’s National Institute for Allergies and Infectious Diseases.

Johns Hopkins Medicine is one of more than 50 clinical trial sites across the United States for ACTIV-2, which plans to test several investigational medicines to see if they are safe and effective against COVID-19 in outpatients with mild to moderate symptoms. The ultimate goal is to develop treatments that can stop the disease from worsening so that people don’t have to go to the hospital.

Participants in the trial must be adults ages 18 and older who have tested positive for COVID-19 within the previous seven days and have been at home with mild to moderate symptoms. Each person will be randomly placed into either a group that will receive the drug under study or one that will get a placebo. Patients will be followed for six months.

“The first drug we are testing is the monoclonal antibody LY-CoV555 (also known as LY3819253) which keeps SARS-CoV-2 [the virus that causes COVID-19] from binding to the cells it targets for attack,” says Kelly Dooley, M.D., Ph.D., associate professor of medicine at the Johns Hopkins University School of Medicine and one of the leaders of the Johns Hopkins Medicine ACTIV-2 program. “LY-CoV555 was copied from an antibody isolated in the blood of a patient who recovered from COVID-19. Preliminary evidence from earlier trials suggests that it could be effective at reducing the duration of symptoms and the amount of virus being shed by patients, both of which could mean fewer hospitalizations.”

The hardest part of conducting the ACTIV-2 trial at Johns Hopkins Medicine and other testing centers, say the researchers involved, may be recruitment.

“Outpatients with milder cases of COVID-19 are likely to believe that clinical trials are only for seriously ill patients who have no other treatment options, so they probably don’t think of themselves as candidates,” says Mark Sulkowski, M.D., professor of medicine at the Johns Hopkins University School of Medicine and chief of the infectious diseases division at Johns Hopkins Bayview Medical Center, where the ACTIV-2 trial is being conducted. He also serves as the director of the COVID-19 Clinical Research Center within the Johns Hopkins Institute for Clinical and Translational Research.

“However, a clinical trial to get effective therapies into practice for outpatients may actually be more critical toward curtailing the spread of COVID-19, because they’re the ones, not hospitalized patients, who are likely to pass the virus to others,” Sulkowski adds. “Furthermore, these treatments have the potential to reduce the risk of serious illness and hospitalization due to COVID-19.”

COVID-19 outpatients who enroll in the ACTIV-2 trial will be examined and treated within portable isolation rooms separated from the other facilities at Johns Hopkins Bayview. These clinical research units (CRUs) are steel-walled storage containers that have been converted into medical stations complete with self-contained air conditioning and heating, negative air pressure exhaust and virus-trapping filters; standard hospital electrical and lighting systems; Wi-Fi; emergency backup power and easily sanitized surfaces.

“The CRUs enable us to take care of participants with coronavirus safely and comfortably — giving them intravenous medications, performing virus detection tests and carrying out the procedures required to make ACTIV-2 successful — while keeping them separated from others,” says Dooley.

“We really are grateful for the volunteers who are willing to sign up for clinical trials, even while feeling ill,” she adds. “It is only with their help that we will develop the safe, effective outpatient treatments so desperately needed.”

For more information on the ACTIV-2 outpatient clinical trial, go to riseabovecovid.org/en.

Johns Hopkins Medicine researchers are working tirelessly to find ways to better understand and eventually eliminate COVID-19 and the virus that causes it. New discoveries, especially those related to clinical therapies and drug regimens, are still early in concept and small in sample size. Rigorous research, testing and peer review, all of which take time, will be required before solid conclusions for clinical care and disease prevention can be made.