The federal government has tapped researchers at the University of Minnesota to oversee international clinical trials of synthetic antibody therapies and whether they can treat COVID-19.
The goal is to harness the natural power of antibodies, produced by the immune system in response to infections, and to mass-produce it against COVID-19, an infectious disease for which there are few proven treatments.
“This has been considered the highest priority study by the NIH,” said James Neaton, the U School of Public Health professor leading the research.
Neaton’s INSIGHT network was selected to oversee the inpatient study based on its experience running international clinical trials of medications for HIV and influenza.
The study is part of the National Institutes of Health’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program and is receiving multimillion-dollar support from federal Operation Warp Speed grants.
Three other large networks will collaborate with INSIGHT and the U, creating a broad group of research hospitals and institutions for enrolling patients and responding to changes in viral activity.
“Hospitals can be activated to enroll participants in epidemic hot spots in the U.S. and around the world,” Neaton said.
The first trial launched this month by the study group is of an antibody product developed by drugmaker Eli Lilly under the name LY-CoV555. Neaton said results could come this fall, by which time the study group could be evaluating several other antibody products under development.
Locally, HCMC is participating in the first trial and enrolling patients, who must be admitted to hospitals for COVID-19 and be taking the antiviral drug remdesivir. A separate U.S. clinical trial group is studying the use of antibody therapies on an outpatient basis.
Neaton said there is growing evidence that a cocktail of drugs is needed to fight severe COVID-19. Remdesivir showed in a drug trial that it could limit viral replication in cells, whereas antibody therapies could give the immune system “extra umph” to prevent infection of the cells in the first place, Neaton said.
“I think they may complement each other,” he said. “These drugs have different methods of action. I liken it to the days in HIV” when researchers discovered that multiple drugs were needed to fight the infection.
Antibodies are produced by the human immune system in response to COVID-19, including so-called neutralizing antibodies that fight off the virus. The initial synthetic therapies are monoclonal, meaning researchers have isolated a single type of neutralizing antibody from COVID-19 patients and reproduced it in large enough quantities to use as therapies.
Drugmakers have the option of launching their own independent trials of their experimental antibody therapies, which are required for U.S. Food and Drug Administration approval. Neaton said the ACTIV program offers one standard approach by which the different therapies can be evaluated.
Each antibody therapy submitted to the ACTIV program will be studied in a blind trial of 1,000 patients — half of whom will receive the therapy and half of whom will receive non-medicating placebos for comparison.
Neaton said an advantage of the large group approach is that studies of different therapies can share patients in the placebo comparison group, which will hasten results amid a pandemic that has caused 65,716 known infections and 1,712 deaths in Minnesota.
Recruitment has been a challenge in other studies of COVID-19 therapies using smaller hospital networks. The U and HCMC also are leading two clinical trials of losartan, ordinarily used to manage blood pressure, against COVID-19.
The local arm of the inpatient study struggled with recruitment because of a slowdown in hospitalizations for COVID-19 in Minnesota, but overall enrollment picked up after surges in cases at participating trial sites in Mississippi and Florida, said Dr. Michael Puskarich, an HCMC emergency physician and a co-leader of the losartan studies.
U a research leader
Minnesota has been a leader of several COVID-19 research initiatives, including the U’s clinical trials that found that hydroxychloroquine didn’t prevent the onset of COVID-19 symptoms and the Mayo Clinic’s leadership of a national convalescent plasma therapy group.
The ACTIV trial of antibody therapies is recruiting only in the U.S. at first because “this is where the patients are, unfortunately,” Neaton said.
Antibody therapies will be evaluated primarily on whether they result in “sustained recovery,” he said.
“Basically, you have to be discharged to your home — not to a rehabilitation center or an intermediate care facility — but essentially where you were living before you were infected,” Neaton said. “And you have to be there for two weeks, essentially still healthy, in order to count you as a success.”
Researchers also will follow the patients for 90 days to assess the safety of antibody therapies and whether they result in fewer long-term complications from infections.