I-SPY COVID Trial Sponsored by Quantum Leap Healthcare Collaborative Suggests Addition of Icatibant is Unlikely to Impact Critically Ill COVID-19 Patients

April 15, 2021

SAN FRANCISCO, April 15, 2021 /PRNewswire/ -- The I-SPY COVID Trial, sponsored by Quantum Leap Healthcare Collaborative (QLHC), was designed to rapidly screen agents that show promise for reducing the time to recovery (defined as reduction in oxygen demand) by approximately 50% or risk of mortality in critically ill COVID-19 patients. Today QLHC announced that, in addition to the razuprotafib and apremilast arms, the icatibant portion of the trial has concluded. Icatibant was selected for inclusion in the I-SPY COVID Trial because it is an antagonist of the bradykinin type 2 receptor, an important element of the kallikrein-kinin system responsible for bradykinin signaling and potentially involved in the development of respiratory impairment in COVID-19. There were no safety concerns associated with icatibant in the trial.

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 initial agents for the study were identified through a unique partnership with the COVID R&D Alliance.

"We chose icatibant because of its track record of safety and efficacy in reducing the swelling associated with acute attacks of hereditary angioedema and that its mechanism of action involving bradykinin signaling has been linked to the biology of acute respiratory distress syndrome (ARDS) in COVID-19 patients," said Dr. Kathleen Liu, a co-principal investigator and chaperone (PI) of the icatibant arm of the I-SPY COVID Trial and a professor of medicine at UCSF. "Icatibant did not impact patients critically ill with COVID-19 when compared to those receiving backbone therapy alone."

The Data Monitoring Committee recommended concluding the icatibant arm of the I-SPY COVID Trial after 95 patients enrolled and the agent met the predefined futility criterion: A regimen will be recommended to be dropped from the trial for futility if the treatment has a probability of 90+% of offering no more than a 50% benefit compared to standard treatment (Pr(HR < 1.5) ≥ 0.9). The data from icatibant patients were compared to those from 209 patients concurrently randomized to the control arm, which included a treatment consisting of dexamethasone and remdesivir — backbone therapy. Patients assigned to the icatibant arm received backbone therapy in combination with 30 mg of icatibant by the subcutaneous route every eight hours for six days. After all patients had reached 28 days of follow-up, the data suggested there was a low probability that the addition of icatibant to backbone therapy impacted time to recovery or mortality.

"While this drug did not meet our high bar for improving time to recovery in this population, the I-SPY COVID Trial was successful in quickly achieving its objective of ruling out a beneficial effect of icatibant on the primary endpoint of time to recovery. The study will continue to evaluate other agents with the potential to improve the grave outcomes of this population," said Dr. Derek Russell, an assistant professor of medicine at the University of Alabama at Birmingham (Birmingham, AL) and co-chaperone (PI) of the icatibant arm of the I-SPY COVID Trial.

Dan Curran, Head, Rare Genetics & Hematology Therapeutic Area at Takeda Pharmaceuticals added, "As a part of our ongoing commitment to global health, we are continuously looking for ways to utilize our expertise and our products to address new and emerging threats, including COVID-19. We are proud to have contributed a therapy to the I-SPY COVID Trial, and while the results were not what we'd hoped for, we're grateful that the information collected has the opportunity to provide additional insight into the biology of icatibant in this population and the pathophysiology of ARDS in COVID-19."

Dr. Laura Esserman, founder and co-principal investigator of the I-SPY Trials and director of the Carol Franc Buck Breast Care Center at UCSF, commented, "I wanted to thank Takeda and its management for supporting this trial from its inception and their strong advocacy for pharmaceutical companies to test their currently marketed agents in the setting of critically ill COVID patients; we all know this is a very high risk endeavor and appreciate their actions prioritizing patients."

Investigation into additional agents via the I-SPY COVID Trial are ongoing, with the investigators continuing to rapidly screen treatments to identify highly effective therapeutics; this remains an urgent priority for QLHC and its partners. The I-SPY COVID Trial now includes 22 sites as well as leaders in pulmonary and critical care centers from around the country.

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. For more information, visit www.QuantumLeapHealth.org.

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. For more information, visit www.ispytrials.org.

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SOURCE Quantum Leap Healthcare Collaborative

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For more information, email karyn.digiorgio@quantumleaphealth.org