The University of Minnesota is coordinating a federally funded COVID-19 trial to find out whether purified virus-fighting antibodies from as many as 10 donors can effectively treat one severe case of the infectious disease.
The trial is an extension of the plasma therapies that have received federal emergency use authorization to treat COVID-19 but with uneven results because antibody levels vary in the plasma donated by people who have recovered from the disease.
"If you're a lucky person to get enough of the antibodies in the plasma infusion you receive, it may work," said James Neaton, who directs the U's INSIGHT network that will enroll patients worldwide for the new trial. "But a very high percentage of the plasma infusions that were done had levels that did not seem to achieve the benefit that you would like."
The study treatment is called anti-coronavirus hyperimmune intravenous immunoglobulin, or hIVIG, and is being developed for the trial through a partnership of four pharmaceutical companies.
The National Institute of Allergy and Infectious Diseases (NIAID) formally launched the trial last week, seeking 500 patients through the U's INSIGHT network.
Half will receive hIVIG and the remainder will receive a placebo saline solution for comparison.
All patients must be hospitalized and also receive remdesivir, an approved antiviral drug for COVID-19.
NIAID director Dr. Anthony Fauci said in a statement that the treatment will hopefully "give the immune system a needed boost to suppress SARS-CoV-2 early in the course of illness, nipping the infection in the bud."
Better oxygen management and two proven drugs have reduced COVID-19 mortality and the average length of hospital stay, but there is still pressure to come up with improved treatments in the absence of a vaccine and amid a new wave of infections.
The Minnesota Department of Health on Wednesday reported a total of more than 115,000 infections with the novel coronavirus that causes COVID-19, and 2,180 deaths. The total included 29 deaths newly reported Wednesday, the highest single-day total since June 4.
The 487 Minnesotans admitted to hospitals for COVID-19 in the seven-day period ending Oct. 11 was the highest total since the first peak of the pandemic in May.
"There is a lot of pressure to quickly find treatments particularly for hospitalized patients," Neaton said. "We feel that pressure. It's taken longer to get this trial going actually because of the difficulty of getting enough plasma and enough treatments to begin the study."
Antibody therapies have been hot topics of late, spurred by President Donald Trump's claim last week that an experimental antibody cocktail made by Regeneron was a "cure" for his recent COVID-19 illness.
A synthetic antibody therapy made by Eli Lilly is part of a federally funded COVID-19 trial that paused its recruiting on Tuesday because of unspecified safety concerns found by the data safety and monitoring board that is overseeing it.
The U's INSIGHT group also is leading that trial of hospitalized patients based on its track record of success in coordinating studies of drugs to fight other infections such as influenza, HIV and Ebola.
Pauses in trials are common as enrollees' health problems are evaluated to determine if they are due to the experimental therapies they received.
"It could be that everything will be just fine and things will resume in two weeks," Neaton said. "If not, then we will review the data which we are currently blinded to in order to try to understand what went wrong."
Intravenous immunoglobulin infusions already treat infections such as cytomegalovirus, rabies and hepatitis A but present risks for COVID-19 patients, Neaton said.
The goal is to use a purified and measurable dosage of antibodies from multiple donors and to give it to patients early enough to stop the virus from wreaking havoc in the lungs and other organs.
However, many COVID-19 deaths are not due to the virus, but rather the overreaction by the human immune system to infection.
Neaton said the study will assess whether the hIVIG avoids or exacerbates that immune system response.
Four enrollees have already joined the study, which will recruit at more than 50 sites worldwide — including at HCMC and the Minneapolis VA Medical Center.
Minnesota has been antibody central when it comes to the study of COVID-19 diagnostics and therapies. The U and Mayo Clinic were among the first in the nation to develop and deploy highly accurate tests for COVID-19 antibodies — proteins produced in response to infection with the coronavirus.
Mayo coordinated a national expanded access program in which donor plasma from recovered COVID-19 patients was administered to newly infected patients.
Enrollment halted in August after the program gained more than 105,000 participants and provided enough evidence to the U.S. Food and Drug Administration to grant emergency use authorization for the therapy.
Mayo researchers are now conducting a methodical review of the recipients and their outcomes over time to assess the effectiveness of the single-donor plasma therapies, said Dr. R. Scott Wright, who coordinated the national program.
Initial data to the FDA had suggested plasma reduced COVID-19 mortality, but conclusions were hampered by the lack of a control group who received standard care for comparison.
"We are honored to have been a part of this and humbled by the response from so many patients and hospitals," Wright said.
Neaton said the U-led network hopes to have recruited enough hospitalized COVID-19 patients in December. Analysis after that will determine if antibodies refined from multiple plasma donors improve treatment compared to remdesivir and the usual treatment.
Neaton noted that the U had led a prior study of intravenous immunoglobulin against seasonal influenza, but it failed to show a benefit.
There had been some evidence it worked against illnesses caused by B strains of influenza, and the U was preparing a follow-up study earlier this year when the COVID-19 pandemic emerged and the research agenda changed.