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Clinical Trial
. 2021 May;21(5):675-686.
doi: 10.1080/14712598.2021.1905794. Epub 2021 Apr 9.

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  1 , Rosemarie De Souza  2 , Milind Nadkar  3 , Randeep Guleria  4 , Anjan Trikha  4 , Shashank R Joshi  5 , Subramanian Loganathan  6 , Sivakumar Vaidyanathan  6 , Ashwani Marwah  6 , Sandeep N Athalye  6
Affiliations
Clinical Trial

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 et al. Expert Opin Biol Ther. 2021 May.

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.

Keywords: COVID-19; Itolizumab; acute respiratory distress syndrome; anti-CD6; coronavirus; cytokine release syndrome; immune hyperactivation; immunotherapy.

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Figures

Figure 1.
Figure 1.
Itolizumab mechanism of action in COVID-19 infection
Figure 2.
Figure 2.
CONSORT 2010 flow diagram
Figure 3.
Figure 3.
Mean IL-6 values
Figure 4.
Figure 4.
Mean TNF-α
Figure 5.
Figure 5.
Mean absolute lymphocyte count
See this image and copyright information in PMC

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Grants and funding

The study was funded by Biocon Biologics India Limited and the funders did not have any role in patient recruitment and management.

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