A two-arm, randomized, controlled, multi-centric, open-label phase-2 study to evaluate the efficacy and safety of Itolizumab in moderate to severe ARDS patients due to COVID-19.

Abstract

Objective: Efficacy and safety of Itolizumab, an immunomodulatory mAb, in treating moderate-to-severe acute respiratory distress syndrome (ARDS) due to cytokine release in COVID-19 patients was evaluated in a multi-centric, open-label, two-arm, controlled, randomized, phase-2 study.Methods: Patients were randomized (2:1) to Arm-A (best supportive care [BSC]+Itolizumab) and Arm-B (BSC). Primary outcome of interest was reduction in mortality 30-days after enrollment.Results: Thirty-six patients were screened, five treated as first-dose-sentinels and rest randomized, while four patients were screen-failures. Two patients in Arm-A discontinued prior to receiving one complete infusion and were replaced. At end of 1-month, there were three deaths in Arm-B, and none in Arm-A (p = 0.0296; 95% CI = -0.3 [-0.61, -0.08]). At end of study, more patients in Arm-A had improved SpO2 without increasing FiO2 (p = 0.0296), improved PaO2 (p = 0.0296), and reduction in IL-6 (43 vs 212 pg/ml; p = 0.0296) and tumor necrotic factor-α (9 vs 39 pg/ml; p = 0.0253) levels. Transient lymphopenia (Arm-A: 11 patients) and infusion reactions (7 patients) were commonly reported treatment-related safety events.Conclusion: Itolizumab is a promising, safe and effective immunomodulatory therapy for treatment of ARDS due to cytokine release in COVID-19 patients, with survival and recovery-benefit.

• Authors: Suresh Kumar, Rosemarie De Souza, Milind Nadkar, Randeep Guleria, Anjan Trikha, Shashank R Joshi, Subramanian Loganathan, Sivakumar Vaidyanathan, Ashwani Marwah, Sandeep N Athalye
• Journal: Expert opinion on biological therapy (Expert Opin Biol Ther) Vol. 21 Issue 5 Pg. 675-686 (05 2021) ISSN: 1744-7682 [Electronic] England
• PMID: 33835886 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Antibodies, Monoclonal, Humanized
• Immunologic Factors
• itolizumab

Topics

• Adult
• Antibodies, Monoclonal, Humanized (pharmacology, therapeutic use)
• COVID-19 (complications, immunology)
• Female
• Humans
• Immunologic Factors (pharmacology, therapeutic use)
• Male
• Middle Aged
• Respiratory Distress Syndrome (drug therapy, etiology, immunology)
• SARS-CoV-2 (drug effects, immunology)
• Severity of Illness Index
• Treatment Outcome
• COVID-19 Drug Treatment