tetano
Editor, Senior Moderator
Expert Opin Biol Ther
. 2021 Apr 9;1-12.
doi: 10.1080/14712598.2021.1905794. Online ahead of print.
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
Suresh Kumar[SUP] 1 [/SUP], Rosemarie De Souza[SUP] 2 [/SUP], Milind Nadkar[SUP] 3 [/SUP], Randeep Guleria[SUP] 4 [/SUP], Anjan Trikha[SUP] 4 [/SUP], Shashank R Joshi[SUP] 5 [/SUP], Subramanian Loganathan[SUP] 6 [/SUP], Sivakumar Vaidyanathan[SUP] 6 [/SUP], Ashwani Marwah[SUP] 6 [/SUP], Sandeep N Athalye[SUP] 6 [/SUP]
Affiliations
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-? (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.
Keywords: COVID-19; Itolizumab; acute respiratory distress syndrome; anti-CD6; coronavirus; cytokine release syndrome; immune hyperactivation; immunotherapy.
. 2021 Apr 9;1-12.
doi: 10.1080/14712598.2021.1905794. Online ahead of print.
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
Suresh Kumar[SUP] 1 [/SUP], Rosemarie De Souza[SUP] 2 [/SUP], Milind Nadkar[SUP] 3 [/SUP], Randeep Guleria[SUP] 4 [/SUP], Anjan Trikha[SUP] 4 [/SUP], Shashank R Joshi[SUP] 5 [/SUP], Subramanian Loganathan[SUP] 6 [/SUP], Sivakumar Vaidyanathan[SUP] 6 [/SUP], Ashwani Marwah[SUP] 6 [/SUP], Sandeep N Athalye[SUP] 6 [/SUP]
Affiliations
- PMID: 33835886
- DOI: 10.1080/14712598.2021.1905794
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-? (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.
Keywords: COVID-19; Itolizumab; acute respiratory distress syndrome; anti-CD6; coronavirus; cytokine release syndrome; immune hyperactivation; immunotherapy.