Clinical experience with JAK2 inhibitors in COVID-19
Study ID no | Brief title of the study | Promoter/Sponsor | Status (first posted) | Patient’s condition/inclusion criteria | No of patients | Study type | Study phase | Centers | Intervention/drugs | Primary outcome measures | Reference |
June 2020 (published) | COVID-19-induced (mild to severe) pneumonia | 4 | Cases report | Pilot study | Monocentric | Baricitinib |
| Stebbing et al117 | |||
NCT04438629 | Evaluation of Immune Response in COVID-19 Patients (IMMUNOVID) | Azienda Ospedaliera Universitaria Integrata Verona (sponsor) and Pederzoli Hospital of Peschiera, Italy | March–June 2020 (published), recruiting | COVID-19-induced pneumonia | 88 (20 on baricitinib) | Observational, longitudinal, prospective | Bicentric | Baricitinib, 4 mg two times per day 2 days, 4 mg/day 7 days |
| Bronte et al118 | |
NCT04358614 | Baricitinib Therapy in COVID-19: A Pilot Study on Safety and Clinical Impact | Hospital of Prato, Italy | completed (published October 2020) | COVID-19 moderate pneumonia | 12 patients in the pilot study 191 (113 on baricitinib) in the second phase | Observational, longitudinal, retrospective | Phase 2 Phase 3 | Multicentric (seven in Italy) | Baricitinib 4 mg/d and antiviral therapy (lopinavir/ritonavir) for 2 weeks vs SOC (hydroxychloroquine and lopinavir/ritonavir) for 2 weeks | Mortality rate | Cantini et al120 |
NCT04401579 | Adaptive COVID-19 Treatment Trial 2 | US National Institute of Allergy and Infectious Diseases | Completed (published March 2021) | COVID-19 hospitalized patients | 1033 (515 on baricitinib) | Interventional, randomized, double-blind, placebo-controlled | Phase 3 | Multicentric (67 international centers) | Remdesivir plus baricitinib 4 mg/d, up to 2 weeks vs Remdesivir plus placebo | Time to recovery | Kalil et al121 |
NCT04421027 | A Study of Baricitinib (LY3009104) in Participants With COVID-19 (COV-BARRIER) | Eli Lilly and Company | Completed (published August 2021) | O2-dependent COVID-19 patients with risk indicators of aggravation | 1585 | Interventional, randomized, double-blind, placebo-controlled | Phase 3 | Multicentric | Baricitinib 4 mg/d and SOC for 2 weeks vs Placebo and SOC for 2 weeks |
| Marconi et al124 |
NCT04469114 | Tofacitinib in Hospitalized Patients With COVID-19 Pneumonia (STOP-COVID) | Hospital Israelita Albert Einstein, Brazil (sponsor) | Completed (published) | COVID-19 hospitalized patients with pneumonia | 289 | Interventional, randomized, double-blind, parallel-design, placebo-controlled | Phase 3 | Multicentric (15 in Brazil) | Tofacitinib, 10 mg Twice daily up to 14 days vs Placebo | Death or respiratory failure until Day 28 | Guimaraes et al131 |
Hammersmith Hospital, London, UK | June 2020 (published) | HSCT for CML Diabetes Male | 1 | Case report | Monocentric | Tocilizumab 8 mg/kg (two doses, no effect) Ruxolitinib 5 mg Twice daily 3 days, 10 mg Twice daily 8 days, 5 mg Twice daily 10days | Case report (severe disease) | Innes et al142 | |||
Aachen University Hospital, Aachen, Germany | May 2020 (published) | MF high-risk for COVID-19 (arterial hypertension, obesity, hyperuricemia, chronic kidney disease) Male | 1 | Case report | Monocentric | Ruxolitinib, 10 mg BD (patient on drug before COVID-19) | Case report (mild disease) | Koschmieder et al143 | |||
No 47 (Italian Agency for Drug (AIFA) and Istituto Spallanzani) No 17 104 (RUXO-COVID (institutional ethic committee in Florence) | RUXO-COVID | Azienda Ospedaliera-Universitaria Careggi, Florence, Italy | April-May 2020 (inclusions) August 2020 (published) | Severe COVID-19 (no mechanical ventilation at diagnosis) | 34 | Observational, prospective | Monocentric | Ruxolitinib (compassionate use), 5 mg Twice daily 1–2 days, 10 mg Twice daily 1–2 days, |
| Vannucchi et al144 | |
Schwarzwald–Baar–Klinikum Villingen-Schwenningen, Germany | March-April 2020 (inclusions), June 2020 (published) | Severe COVID-19 | 105 consecutive patients, 14 patients on ruxolitinib | Retrospective, observational (multidisciplinary board decision on specific medical treatment) | pilote case series | Monocentric | Ruxolitinib, 7.5 mg Twice daily 1–7 days to 15 mg Twice daily | CIS | La Rosee et al145 | ||
NCT04338958 | Ruxolitinib in COVID-19 Patients With Defined Hyperinflammation (RuxCoFlam) | University of Jena, Germany (Sponsor) | Completed (published) | COVID-19 patients with hyperinflammation (COVID-19 Inflammation Score (CIS) ≥10/16) | 193 | Interventional, single arm (open), non-randomized | Phase 2 | Multicentric | Ruxolitinib, 10 mg Twice daily to 20 mg Twice daily | Improvement in CIS | La Rosee et al145 |
NCT04337359 (expanded access for ruxolitinib) | Ruxolitinib Managed Access Program for Patients Diagnosed With Severe/Very Severe COVID-19 Illness | Policlinico S.Marco Gruppo San Donato University and Research Hospital, Zingonia, Bergamo, Italy | March–April 2020 (inclusions), November 2020 (published) | Severe COVID-19 (no mechanical ventilation at diagnosis) | 75 (32 on ruxolitinib, 43 as control) | Interventional, non-randomized | Monocentric | Ruxolitinib, 5 mg Twice daily 7 days, 5 mg/d 3 days + Methyl-prednisolone 1 mg/kg/day IV 3 days, 0.5 mg/kg/day 5 days, then oral prednisone tapered over 2 weeks | Evolution of the COVID-19 disease | D'Alessio et al146 | |
February 2020 (included), July 2020 (published) | Severe COVID-19 | 41 (20 on ruxolitinib, 21 as control) | Interventional, prospective, single-blind, randomized and controlled | Phase 2 | Multicentric (three in China) | Ruxolitinib, 5 mg Twice daily and standard-of-care (SOC) vs Placebo (C vitamin, 100 mg Twice daily) and SOC | Time to clinical improvement | Cao et al147 | |||
trial register no. 81 April 2020 (Italian COVID-19 Ethical Committee) NCT04361903 | Ruxolitinib for the Treatment of ARDS in Patients With COVID-19 Infection (COVID-19: Ruxolitinib for the Treatment of cytokinE Storm resPiratory dIstREss Syndrome. RESPIRE Study) | August 2020 (published) | COVID-19-related ARDS | 18 | Observational, retrospective | Multicentric (three in Italy) | Ruxolitinib, 20 mg Twice daily 2 days and de-escalation to 5 mg Twice daily | Degree of respiratory impairement | Capochiani et al148 | ||
MPN-COVID | European Leukemia Network | MPNs | 175 | Observational, retrospective | Multicentric, in 38 European centers (France, Germany, Italy, Poland, Spain and the UK) |
| Barbui et al151 | ||||
Royal Berkshire Hospital NHS Foundation Trust, Reading, UK | COVID-19 with secondary haemophagocytic lymphohistiocytosis (sHLH) Patients with medical history of lymphoma | 2 | Cases report | Monocentric | Ruxolitinib + Tocilizumab | Case report (severe diseases) | Portsmore et al153 | ||||
NCT04362137 | Phase 3 Randomized, Double-blind, Placebo-controlled Multi-center Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm (RUXCOVID) | Novartis Pharmaceuticals | Completed | COVID-19-related cytokine storm | 432 | Interventional, randomized, double-blind, placebo-controlled | Phase 3 | Multicentric | Ruxolitinib, 5 mg Twice daily vs Placebo |
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NCT04377620 | Assessment of Efficacy and Safety of Ruxolitinib in Participants With COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT) | Incyte Corporation | Terminated | COVID-19-associated ARDS AND intubation and mechanical ventilation | 211 | Interventional, randomized, double-blind, placebo-controlled | Phase 3 | Multicentric | Ruxolitinib, 5 mg or 15 mg, Twice daily and SOC vs Placebo and SOC | Death rate | |
NCT04402866 | TD-0903 for ALI Associated With COVID-19 | Theravance Biopharma (sponsor) | completed (published) | Oxygen-requiring patients with COVID-19-associated:
| 235 | Randomized, double-blind, parallel-group trial, placebo-controlled | Phase 2 | Multicentric (the UK, Moldova and Ukrain) | Nezulcitinib (ascending-dose cohorts from 1 to 10 mg/day) for up to 7 days vs Placebo | No of respiratory failure-free days (Baseline through Day 28) | Singh et al157 |
ALI, acute lung injury; ARDS, acute respiratory distress syndrome; ECMO, extracorporeal membrane oxygenation; JAK, Janus kinases; MF, myelofibrosis.