Quantum Leap Healthcare Collaborative (QLHC), the sponsor of the I-SPY COVID Trial, announced that cenicriviroc (CVC) has been dropped from the trial due to futility, based on the low likelihood of success. CVC was chosen for testing because it is a CCR2/5 inhibitor, which has been hypothesized to potentially prevent fibrosis linked to the inflammation that accompanies critical illness associated with COVID-19.
The I-SPY COVID Trial is a phase II, open label, adaptive platform trial being conducted in critically ill COVID-19 patients who are receiving high-flow oxygen or mechanical ventilation. The trial was designed to rapidly screen agents to find those with the best chance of reducing time to recovery (defined as reduction in oxygen demand) by approximately 50% and reducing risk of death. The I-SPY COVID Trial identified the initial agents for the study through a unique partnership with the COVID R&D Alliance, and CVC was the first oral agent identified and approved to go forward through this mechanism. The I-SPY COVID Trial included 18 sites at the time of evaluation, and there are now 26 participating sites.
QLHC discontinued testing of CVC in the I-SPY COVID Trial because, after 94 patients enrolled, the agent met the predefined futility criterion, defined as at least 90% probability that the hazard ratio for time to recovery is less than 1.5 compared to the control arm. The data from CVC patients were compared to those from 220 patients concurrently randomized to the control, which included backbone therapy (consisting of dexamethasone and remdesivir). Patients assigned to the CVC arm received backbone therapy in combination with 150 mg orally twice daily of CVC (load dose on Day 1 only of 450 mg) for a minimum of 14 days and up to 28 days. Based on a near final analysis of this interim data cut, there is a low probability that the addition of CVC to backbone therapy reduces time to recovery, as per pre-specified criteria for continuation. Other endpoints assessed, including mortality, did not show a statistically significant difference between CVC and placebo at this interim data cut. As a result, the Data Monitoring Committee recommended closing the arm. The study did not identify new safety signals for CVC in the setting of critically ill patients.
Dr. D. Clark Files, an I-SPY COVID Trial co-investigator and chaperone (PI) of the CVC arm, and an associate professor of medicine at Wake Forest University (Winston Salem, North Carolina), commented, “The I-SPY COVID Trial demonstrated that CVC did not substantially improve recovery in patients critically ill with COVID-19. It is possible that this drug may be promising for treating other types of acute lung injury, or other populations of less critically ill COVID-19 patients and future trials may be warranted.”
“While we were disappointed that CVC did not succeed in substantially altering the clinical course of patients with severe COVID-19 when added to dexamethasone and remdesivir, we were glad to know this quickly and continue to test other agents,” continued Dr. Sheetal Gandotra, an assistant professor of medicine at the University of Alabama at Birmingham and co-chaperone of the CVC arm of the I-SPY COVID Trial.
Kathleen Liu, a professor of medicine at UCSF and co-principal investigator for the I-SPY COVID Trial, added, “CVC did not meet the high bar we set for improving time to recovery. Finding effective agents for people who become critically ill from COVID-19 remains an urgent priority.”
“We were pleased to work with the I-SPY COVID Trial team and Quantum Leap Healthcare Collaborative to test an agent in our pipeline that had a chance to alter the course of this devastating condition,” said William Ferguson, PhD, Executive Director, Clinical Development, AbbVie. “We are hopeful that some of the drugs being tested by I-SPY will prove helpful and safe in critically ill COVID-19 patients. This is a worthwhile endeavor and we appreciate the opportunity to be a part of the I-SPY network.”
This study is a collaboration between members of Quantum Leap, the U.S. Food and Drug Administration and the COVID R&D Alliance, which AbbVie is a member of with more than 20 of the world’s leading biopharmaceutical and life science companies. In addition, the Biomedical Advanced Research and Development Authority (BARDA), part of HHS within the office of the Assistant Secretary for Preparedness and Response, and Joint Program Executive Office, a part of the Department of Defense, are also part of this collaboration under the Medical Chemical, Biological, Radiological, and Nuclear (CBRN) Defense Consortium (MCDC).
About Quantum Leap Healthcare Collaborative
Quantum Leap Healthcare Collaborative is a 501C(3) charitable organization established in 2005 as a collaboration between medical researchers at University of California, San Francisco and Silicon Valley entrepreneurs. Our mission is to integrate high-impact research with clinical processes and systems technology, resulting in improved data management and information systems, greater access to clinical trial matching and sponsorship, and greater benefit to providers, patients and researchers. Our goal is to improve and save lives. Quantum Leap provides operational, financial, and regulatory oversight to the I-SPY Trials.
About the I-SPY Trials
The I-SPY Trials were designed to rapidly screen promising experimental treatments and identify those most effective in specific patient subgroups based on molecular characteristics (biomarker signatures). The trial is a unique collaborative effort by a consortium that includes the Food and Drug Administration (FDA), industry, patient advocates, philanthropic sponsors, and clinicians from 20 major U.S. medical research centers. Under the terms of the collaboration agreement, Quantum Leap Healthcare Collaborative is the trial sponsor and manages all study operations.