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
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
|---|---|
| Enthalten in: |
Expert opinion on biological therapy - 21(2021), 5 vom: 01. Mai, Seite 675-686 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kumar, Suresh [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.05.2021 Date Revised 11.11.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1080/14712598.2021.1905794 |
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| funding: |
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|---|---|
| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM323909892 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
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| 041 | |a eng | ||
| 100 | 1 | |a Kumar, Suresh |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a 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 |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 17.05.2021 | ||
| 500 | |a Date Revised 11.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Itolizumab | |
| 650 | 4 | |a acute respiratory distress syndrome | |
| 650 | 4 | |a anti-CD6 | |
| 650 | 4 | |a coronavirus | |
| 650 | 4 | |a cytokine release syndrome | |
| 650 | 4 | |a immune hyperactivation | |
| 650 | 4 | |a immunotherapy | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a Immunologic Factors |2 NLM | |
| 650 | 7 | |a itolizumab |2 NLM | |
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| 700 | 1 | |a De Souza, Rosemarie |e verfasserin |4 aut | |
| 700 | 1 | |a Nadkar, Milind |e verfasserin |4 aut | |
| 700 | 1 | |a Guleria, Randeep |e verfasserin |4 aut | |
| 700 | 1 | |a Trikha, Anjan |e verfasserin |4 aut | |
| 700 | 1 | |a Joshi, Shashank R |e verfasserin |4 aut | |
| 700 | 1 | |a Loganathan, Subramanian |e verfasserin |4 aut | |
| 700 | 1 | |a Vaidyanathan, Sivakumar |e verfasserin |4 aut | |
| 700 | 1 | |a Marwah, Ashwani |e verfasserin |4 aut | |
| 700 | 1 | |a Athalye, Sandeep N |e verfasserin |4 aut | |
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