URMC / Clinical & Translational Science Institute / Stories / August 2023 / Immune Modulators Have Mixed Results on COVID Pneumonia

Immune Modulators Have Mixed Results on COVID Pneumonia

Patient being treated by two health care providers in full protective garb with a sign on the glass reading "DANGER, COVID-19" Throughout the COVID pandemic, the UR CTSI led an “air traffic control” effort to help coordinate COVID-related clinical trials at the University of Rochester Medical Center (URMC). Through the UR CTSI’s connection with the national Trial Innovation Network (TIN), the Medical Center joined the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-1) Immune Modulators clinical trial in December of 2020.

Now, results from phase three of the ACTIV-1 trial are in, and they are… complicated. Published in the Journal of the American Medical Association (JAMA), the results show that three immune modulators (which normally tamp down the effects of an overactive immune system) did not speed recovery for patients hospitalized with COVID pneumonia. On the other hand, two of the immune modulators appear to have improved survival 28 days after treatment, but this effect cannot be considered statistically significant due to the study’s gatekeeping design.

The JAMA article and an editorial about the trial call for further investigation of abatacept and infliximab, the two immune modulators that may have improved survival. They also point out that lessons learned from the trial, including the strengths and weaknesses of the trial design, will inform future pandemic-time trials.

ACTIV-1’s adaptive trial design, which allowed study leaders to modify the trial’s course as data accumulated, was hugely helpful in the early days of the pandemic when knowledge about the virus was scant. The trial also used a common placebo arm compared against three different treatment arms, which “allowed us to control for biases while also minimizing the number of persons that were assigned to placebo (standard of care treatment),” said Christopher Palma, MD, an associate professor of Allergy, Immunology and Rheumatology, who served as principal investigator of the ACTIV-1 trial at URMC. “Few other trials during the pandemic did this.”

Palma and co-investigator Caroline Quill, MD, associate professor of Pulmonary Diseases and Critical Care at URMC, joined ACTIV-1 and enrolled 51 local patients after receiving information about the trial from the TIN, a collaborative initiative within the Clinical and Translational Science Awards (CTSA) Program.

“Accepting and onboarding a trial through the TIN has some advantages compared to a traditional industry-sponsored study,” said Palma. “There are accelerated mechanisms to aid startup which include cohort assessment tools, like TriNetX, and there are often uniform contracts that are easy to interpret and apply to your own budgets, and make startup an easier process.”

As a member of the CTSA Program, the UR CTSI provided the vital connection to the TIN that made this opportunity possible. More than half of all CTSA Program sites, like the UR CTSI, contributed crucial infrastructure and expertise to quickly implement the trial at their institutions.

Read the full JAMA article and JAMA editorial.

Watch Palma’s testimonial about participating in ACTIV-1 through the TIN.

Michael Hazard | 8/18/2023