MINNEAPOLIS — 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 an infectious disease in COVID-19 for which there are few proven treatments.
“This has been considered the highest priority study by the NIH,” said James Neaton, the U biostatistics professor who is leading the research.
Neaton’s INSIGHT network was selected to oversee the study based on its experience running international clinical trials of medications for HIV and influenza.
The antibody 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 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 earlier this month by the study group is of an antibody product developed by drugmaker Eli Lilly under the name LY-CoV555. Neaton said the group could be studying several other versions under development by drug companies by this fall.
Locally, Hennepin County Medical Center is participating in the first trial and enrolling patients, who must be admitted to hospitals for COVID-19 and taking the antiviral drug remdesivir.
Neaton said there is growing evidence that a cocktail of drugs is needed to fight severe COVID-19. Remdesivir was proved in a drug trial earlier this year to limit viral replication by infected cells, whereas antibody therapies could prevent the cells from becoming infected in the first place.
“I think they may complement each other,” Neaton said. “These drugs have different methods of action. I liken it to the days in HIV when we learned that one drug alone didn’t work, and two drugs didn’t work very well.”
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 and compared.
Each antibody therapy submitted to the ACTIV program will be studied in a blinded 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 alone.
Recruitment has been a challenge in other studies of COVID-19 therapies using smaller hospital networks. The U and Hennepin Healthcare 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 due to a slowdown in hospitalizations for COVID-19 in Minnesota, but enrollment picked up due to surges in cases at participating trial sites in Mississippi and Florida, said Dr. Michael Puskarich, an emergency physician for Hennepin Healthcare and a co-leader of the losartan studies.
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 cause “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 whether antibody therapies result in fewer long-term complications from infections.
©2020 Star Tribune (Minneapolis)