Stony Brook Medicine has launched an FDA-approved, randomized investigational new drug (IND) trial to determine whether plasma from people who have recovered from COVID-19 can aid in the recovery of patients currently fighting the disease. As part of that effort, the Long Island medical school is partnering with Chembio Diagnostics Inc., of Hauppage, N.Y., whose COVID-19 rapid serological point-of-care test will be used to identify potential plasma donors.

“We have moved at lightning speed,” Elliott Bennett-Guerrero, medical director of perioperative quality and patient safety and vice chair of clinical research and innovation in the Department of Anesthesiology at Stony Brook Medicine, told BioWorld. The hospital has obtained the necessary approval by its ethics board and began enrolling plasma donors on April 9. The first donation of convalescent plasma is expected on Monday, April 13, with patient enrollment potentially beginning the following day.

Study design

The randomized, controlled study aims to enroll 500 patients with active COVID-19 infection at Stony Brook University Hospital. To maximize the potential benefit, 80% of patients will receive convalescent plasma and 20% will get standard plasma. The primary endpoint is ventilator-free days through 28 days after randomization, a commonly used endpoint related to the lungs in intensive care patients. Doctors will also be looking at all-cause survival through 90 days, as well as antibody levels to COVID-19 before and after plasma infusion.

“Our collaboration with Stony Brook Medicine on this important study represents the next step in our COVID-19 initiative,” said Javan Esfandiari, Chembio executive vice president and chief science and technology officer, pointing to the earlier receipt of FDA emergency use authorization for its test. “We are pleased that our unique and proprietary DPP [dual-path platform] technology, which can separately and simultaneously detect and measure IgG and IgM antibodies specific to COVID-19, is the assay of choice for Stony Brook Medicine.”

Most hospitals in the U.S. are attempting to use convalescent plasma to potentially boost the immune response of critically ill COVID-19 patients. However, without a control group, there’s no way of knowing if the approach is really effective, said Bennett-Guerrero, who is leading the study at Stony Brook. “There’s a tremendous amount of enthusiasm about convalescent plasma, and we certainly hope it saves lives. However, we really don’t know for this specific virus whether it’s safe and effective.”

He pointed to a multicenter, randomized, NIH-funded trial of hospitalized patients treated with convalescent plasma or standard plasma. The results, published in 2019 in The Lancet, showed no benefit with convalescent plasma.

‘Ramping up rapidly’

“We are ramping up rapidly with the hope of very quickly identifying at least 200 plasma donors and then enrolling many, many people every day in the hospital, because there is a large unmet need,” Bennett-Guerrero said. “We probably have at least 300 patients right now in the hospital who would potentially be eligible to be in this trial.”

Roughly one-third of those patients are on ventilators, he said, adding the trial is targeting about two people who are not on ventilators for each person who is on a ventilator. The hope is that by administering convalescent plasma to patients earlier in the course of infection, doctors can prevent their condition from worsening.

He underscored that the pace of enrollment will depend on the plasma supply, but added “we are cautiously optimistic that we will be able to scale this up quickly.”

For people to be eligible to donate, they must have a documented COVID-19 infection, be fully recovered for at least 14 days, have high antibody levels to the virus and meet standard requirements for donating blood products.

Fingerstick test has high level of accuracy

MR1 and MR2 analyzers for DPP COVID-19 test. Credit: Chembio Diagnostics Inc.

Chembio’s DPP COVID-19 test runs on the company’s MR1 and MR2 analyzers. Gail Page, a Chembio board member, said Stony Brook Medicine is using the MR2 analyzer because of its enhance interface capabilities and other features and benefits. “The analyzer is critical as it provides a numerical readout and, therefore, removes errors in interpretation and allows for monitoring of a patient’s immune system,” Page told BioWorld.

Blood samples are drawn via a simple fingerstick, and results are provided in about 15 minutes. “The high sensitivity and specificity greater than 95% has been demonstrated throughout our entire portfolio,” Page said.

Stony Brook began working with Chembio earlier in the course of the outbreak to provide blood samples from patients to help validate the DPP test, Bennett-Guerrero said. “At this point, we have a high level of confidence in the quality of the assay.”

He noted, however, that most assays, including Chembio’s, just indicate if there are antibodies in the blood that bind to antigens expressed by COVID-19. “We don’t know whether those are functional antibodies or not … and will block and neutralize any virus that’s in the blood.

“A neutralizing antibody assay is pretty complex to set up,” he said, adding he is not aware of any tests that measure neutralizing antibodies in a rapid fashion.

Other plasma recovery efforts

The idea of using convalescent plasma to treat viral infections dates back more than a hundred years. The therapy was used during the 1918 flu pandemic, as well as for polio, measles, chickenpox and pertussis. In recent decades, it has been used to treat MERS, H1N1 and H5N1 avian flu and Ebola.

The Feinstein Institutes for Medical Research, the research arm of Northwell Health, reported last week that it has joined a nationwide network led by the Mayo Clinic to collect convalescent plasma to fight COVID-19. The plasma it collects will initially be injected in patients at North Shore University Hospital and Lord island Jewish Medical Center, with additional Northwell Health hospitals to be added shortly.

To increase understanding of the immune response to COVID-19, Feinstein is urging people who register as donors to agree to participate in future COVID-19 research, including investigation of a possible vaccine.

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