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

Autor: Randeep Guleria, Ashwani Marwah, Rosemarie de Souza, Suresh Kumar, Sivakumar Vaidyanathan, Milind Y Nadkar, Subramanian Loganathan, Anjan Trikha, Shashank R Joshi, Sandeep N. Athalye
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Adult
Male
medicine.medical_specialty
ARDS
Coronavirus disease 2019 (COVID-19)
medicine.medical_treatment
Clinical Biochemistry
Itolizumab
coronavirus
immune hyperactivation
Phases of clinical research
Antibodies
Monoclonal
Humanized
Severity of Illness Index
03 medical and health sciences
Immune system
0302 clinical medicine
Internal medicine
Drug Discovery
Severity of illness
Medicine
Humans
Immunologic Factors
Lead (electronics)
Original Research
Pharmacology
Respiratory Distress Syndrome
business.industry
SARS-CoV-2
COVID-19
cytokine release syndrome
Immunotherapy
acute respiratory distress syndrome
Middle Aged
medicine.disease
anti-CD6
COVID-19 Drug Treatment
Clinical trial
Cytokine release syndrome
030104 developmental biology
Cytokine
Treatment Outcome
030220 oncology & carcinogenesis
Female
immunotherapy
business
medicine.drug
Research Article
Zdroj: Expert Opinion on Biological Therapy
article-version (VoR) Version of Record
ISSN: 1744-7682
1471-2598
Popis: 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.
Databáze: OpenAIRE
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