IC14 is a chimeric monoclonal antibody that was selected for inclusion in the trial because targeting CD14 may be an appropriate strategy to modulate the host innate immune response that causes serious illness and organ damage in COVID-19 illness. The testing of IC14 was discontinued at the recommendation of the Data Monitoring Committee (DMC) after 66 subjects were randomized to the IC14 arm and analyzed in the Intent-to-Treat (ITT) population. Patients assigned to the IC14 arm received backbone therapy, including dexamethasone and remdesivir, plus 4 mg/kg of IC14 by intravenous infusion on day 1 and 2 mg/kg on days 2, 3 and 4.
The IC14 results were compared to 76 subjects who were concurrently randomized to the backbone control arm. The graduation criteria were not met, but the futility criteria were partially met. The probability that IC14 could reduce time to recovery was estimated to be 3.4%; the probability that the IC14 arm is superior to the concurrent arm to reduce mortality was estimated to be 62%. After all patients reached 28 days of follow-up, the data suggested there was a low probability that the addition of IC14 to backbone therapy would have an impact on time to recovery or mortality.
The I-SPY COVID Trial was designed to rapidly screen agents that show promise for reducing the time to recovery (defined as reduction in oxygen demand) or risk of mortality in critically ill COVID-19 patients. The study utilizes QLHC’s adaptive platform trial design methodology, which focuses on the simultaneous, efficient assessment of multiple investigational agents. Previous agents assessed in the trial include cenicriviroc, razuprotafib, apremilast, icatibant and famotidine plus celecoxib. An investigational agent arm is recommended for termination due to futility if there is insufficient improvement in recovery or mortality. Specifically, the following futility rules apply:
1. The treatment crosses the 90% probability that the hazard rate for benefit in time to recovery is less than 1.5 compared to standard treatment (Pr(HR < 1.5) ≥ 0.9)
2. Posterior probability for its hazard ratio for overall mortality vs. backbone (adjusted for COVID-19 level status at baseline) is greater than one is greater than or equal to 0.5 (Pr(HRmortality > 1) ≥ 0.5).
IC14 was administered at 24 participating US sites. There were no safety concerns associated with IC14 in the trial.
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 24 sites as well as leaders in pulmonary and critical care centers from around the country.
The I-SPY COVID Trial is a collaboration between members of Quantum Leap, pharmaceutical partners such as Implicit Bioscience and the United States government. This work is supported in part by the Biomedical Advanced Research and Development Authority (BARDA), part of the office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services, and the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, in collaboration with the Medical, Chemical, Biological, Radiological and Nuclear (CBRN) Defense Consortium (MCDC)—(contract MCDC2014-001). The Defense Threat Reduction Agency (DTRA) enables the Department of Defense (DoD), the U.S. Government, and International Partners to counter and deter Weapons of Mass Destruction (WMD) and Emerging Threats.