Baricitinib in Symptomatic Patients Infected by COVID-19: an Open-label, Pilot Study.

Overview

There is no specific antiviral treatment recommended for COVID-19, and no vaccine is currently available. Baricitinib, an anti-Janus kinase inhibitor (anti-JAK) acting against JAK1 and JAK2. The drug was found capable to reduce or interrupt the passage of the virus into target cells, and to inhibit the JAK1- and JAK2-mediated cytokine release. The drug was licensed for the treatment of rheumatoid arthritis at the daily dose of 4 mg/orally, with excellent results in terms of clinical response and a good safety profile. Since baricitinib does not interact with antivirals due to its prevalent renal elimination, it may be used in combination.The evidence on the advantageous action of baricitinib on viral entry and cytokine outbreak constituted the rationale to perform a trial on patients with mild to moderate COVID-19 infection receiving baricitinib combined with antiviral therapy.

Full Title of Study: “Baricitinib Combined With Antiviral Therapy in Symptomatic Patients Infected by COVID-19: an Open-label, Pilot Study”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: June 30, 2020

Detailed Description

Study design. Interventional, open-label, 2-week, prospective trial of a cohort of patients with mild to moderate COVID-19 infection.

Objectives. Primary. To assess the efficacy of baricitinib combined with antiviral therapy in patients with COVID-19-related mild and moderate disease in terms of reduction of the percentage of subjects requiring ICU admission.

Secondary objectives. To describe the clinical findings in a cohort of symptomatic COVID-19-infected subjects; to investigate the role of CRP, IL-6, and TNFα levels as predictor of progression to ARDS; to assess the type and incidence of adverse events (AEs).

Interventions

  • Drug: Baricitinib
    • Baricitinib 4 mg/day/orally combined to antiviral therapy ritonavir for 2 weeks. Baricitinib tablets 4 mg were administered in the morning.

Arms, Groups and Cohorts

  • Experimental: Patients
    • All patients received baricitinib combined to antiviral therapy lopinavir/ritonavir for 2 weeks.
  • Active Comparator: Controls
    • All consecutive patients with mild to moderate COVID-19 infection, older than 18, a during the previous 2 weeks, who were treated with antiviral and/or hydroxychloroquine.

Clinical Trial Outcome Measures

Primary Measures

  • The percentage of patients requiring transfer to ICU as compared with the rate of transfers observed in controls.
    • Time Frame: 2 weeks
    • The percentage of ICU admission in patients and controls will be compared for statistical difference

Secondary Measures

  • The percentage of patients achieving the remission; CRP, IL-6 and TNFα values at baseline and during the treatment course; the number of AEs.
    • Time Frame: 2 weeks
    • CRP values will be evaluated for prediction of disease worsening.

Participating in This Clinical Trial

Inclusion Criteria

  • All consecutive patients with mild to moderate COVID-19 infection
  • Age >18 years,
  • Clinical diagnosis of COVID19 infection
  • Patients should present fever, cough and myalgia and weakness and radiological findings of pneumonia.
  • All patients should be willing and able to provide written informed consent prior to performing study procedures.

Exclusion Criteria

  • Age less than 18
  • History of thrombophlebitis.
  • Patient with latent tuberculosis infection (Quantiferon test).
  • Pregnancy and lactation.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 85 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Hospital of Prato
  • Provider of Information About this Clinical Study
    • Principal Investigator: Fabrizio Cantini, Head of Rheumatology Department, Principal investigator – Hospital of Prato
  • Overall Official(s)
    • Fabrizio Cantini, MD, Study Director, Hospital of Prato, Italy
  • Overall Contact(s)
    • Fabrizio Cantini, MD, +393408075607, fbrzcantini@gmail.com

References

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Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum in: Lancet. 2020 Jan 30;:.

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11. Erratum in: Lancet. 2020 Mar 28;395(10229):1038. Lancet. 2020 Mar 28;395(10229):1038.

Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 May 7;382(19):1787-1799. doi: 10.1056/NEJMoa2001282. Epub 2020 Mar 18.

Richardson P, Griffin I, Tucker C, Smith D, Oechsle O, Phelan A, Stebbing J. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Lancet. 2020 Feb 15;395(10223):e30-e31. doi: 10.1016/S0140-6736(20)30304-4. Epub 2020 Feb 4.

Bechman K, Subesinghe S, Norton S, Atzeni F, Galli M, Cope AP, Winthrop KL, Galloway JB. A systematic review and meta-analysis of infection risk with small molecule JAK inhibitors in rheumatoid arthritis. Rheumatology (Oxford). 2019 Oct 1;58(10):1755-1766. doi: 10.1093/rheumatology/kez087.

Stebbing J, Phelan A, Griffin I, Tucker C, Oechsle O, Smith D, Richardson P. COVID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect Dis. 2020 Apr;20(4):400-402. doi: 10.1016/S1473-3099(20)30132-8. Epub 2020 Feb 27.

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