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Cochrane COVID-19 Study Register
Study record
Kumar 2020aqFirst Published: 2020 Dec 19Updated Date: 2021 Apr 11

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 (preprint)

  1. Study Type
  2. Interventional
  1. Study Aim
  2. Treatment and Management
  1. Study Design
  2. Parallel/Crossover
  1. Intervention Assignment
  2. Randomised
  1. Population (8)
  2. Male and Female
  3. Acute Respiratory Distress Syndrome
  4. Cytokine storm
  5. Severe COVID-19
  6. Moderate COVID-19
  7. Adult
  1. Intervention (2)
  2. Itolizumab
  3. Usual Care
  1. Comparison (1)
  2. Usual Care
  1. Outcome (7)
  2. All Cause Mortality
  3. Tumour Necrosis Factor Level
  4. Infusion Site Reactions
  5. Lymphopenia
  6. PaO2
  7. Oxygen Saturation
  8. Interleukin-6
Reference record

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 (preprint)

Kumar S, de Souza R, Nadkar M, Guleria R, Trikha A, Joshi SR, Loganathan S, Vaidyanathan S, Marwah A, Athalye SN
Unpublished article (preprint)
Report Results
An uncontrolled increase in cytokine production may lead to systemic hyperinflammation, vascular hypo-responsiveness, increased endothelial permeability, hypercoagulation, multi-organ dysfunction and eventually death in moderate to severely ill COVID-19 patients. Targeting T-cells, an important driver of the hyperinflammatory response, in the treatment of COVID-19, could potentially reduce mortality and improve survival rates. Itolizumab is an anti-CD6 humanized monoclonal antibody with an immunomodulating action on Teffector cells that downregulates T-cell activation, proliferation and subsequent production of various chemokines and cytokines. The efficacy and safety of Itolizumab for the treatment of cytokine release syndrome in patients with moderate to severe acute respiratory distress syndrome (ARDS) due to COVID-19 was evaluated in a multi-centric, open-label, two-arm, controlled, randomized, phase 2 study. Eligible patients were randomized (2:1) to arm A (best supportive care + Itolizumab) and arm B (best supportive care). The primary outcome of interest was reduction in all-cause mortality 30 days after enrolment. Thirty-six patients were screened, 5 were treated as first dose sentinels and the rest were randomized, whilst 4 patients were considered screen failures. Two patients in the Itolizumab treatment arm discontinued prior to receiving the first dose and were replaced. At the end of 1 month, there were 3 deaths in arm B, and none in arm A (p= 0.0296). At the end of the follow-up period, 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 pg/ml vs 212 pg/ml; p=0.0296) and tumor necrotic factor-α (9 pg/ml vs 39 pg/ml; p=0.0253) levels. Itolizumab was generally safe and well tolerated, and transient lymphopenia (11 patients in Arm A) and infusion reactions (7 patients) were the commonly reported treatment related safety events. These encouraging results indicate that larger clinical trials are warranted to establish the role of Itolizumab in controlling immune hyperactivation in COVID-19..Clinical TrialCTRI/2020/05/024959 [Preprints are preliminary reports of work that have not been peer reviewed. Refer to the original preprint or preprint server for specific information about the individual preprint.]
Reference record

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

Kumar S, De Souza R, Nadkar M, Guleria R, Trikha A, Joshi SR, Loganathan S, Vaidyanathan S, Marwah A, Athalye SN
Journal article(Kumar) MAMC Medical College and Lok Nayak Jai Prakash Narayan Hospital, New Delhi, India (De Souza) Topiwala National Medical College & B. Y. L. Nair Charitable Hospital, Mumbai, Maharashtra, India (Nadkar) Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India (Guleria, Trikha) All India Institute of Medical Sciences, New Delhi, India (Joshi) Indian College of Physicians and Lilavati Hospital, Mumbai, Maharashtra, India (Loganathan, Vaidyanathan, Marwah, Athalye) BengaluruKarnatakaIndia
Report Results
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