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

• ClinicalTrials.gov Identifier: NCT04320277
• Recruitment Status: Unknown
• First Posted: March 24, 2020
• Last Update Posted: April 22, 2020
• Sponsor: Hospital of Prato
• Information provided by (Responsible Party): Fabrizio Cantini, Hospital of Prato

Tracking Information

• First Submitted Date: March 20, 2020
• First Posted Date: March 24, 2020
• Last Update Posted Date: April 22, 2020
• Estimated Study Start Date: May 16, 2020
• Estimated Primary Completion Date: June 30, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 23, 2020)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 23, 2020)

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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Baricitinib in Symptomatic Patients Infected by COVID-19: an Open-label, Pilot Study.
• Official Title: Baricitinib Combined With Antiviral Therapy in Symptomatic Patients Infected by COVID-19: an Open-label, Pilot Study
• Brief Summary: 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.

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).

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

Patients. All consecutive patients with mild to moderate COVID-19 infection, older than 18, Patients should present fever, cough and myalgia and weakness and radiological findings of pneumonia.

Controls. All consecutive patients with mild to moderate COVID-19 infection, older than 18, admitted during the previous 2 weeks, who were treated with antiviral and/or hydroxychloroquine.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Pharmacological Action

Intervention

Drug: Baricitinib

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

Other Name: Lopinavir/Ritonavir tablets 250 mg/bid

Study Arms

• Experimental: Patients
  All patients received baricitinib combined to antiviral therapy lopinavir/ritonavir for 2 weeks.
  Intervention: Drug: Baricitinib
• 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.
  Intervention: Drug: Baricitinib

Publications *

• Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017 Jul;39(5):529-539. doi: 10.1007/s00281-017-0629-x. Epub 2017 May 2. Review.
• Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.
• 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, Rawling M, Savory E, 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. Erratum in: Lancet. 2020 Jun 20;395(10241):1906.
• 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.
• Benucci M, Damiani A, Infantino M, Manfredi M, Quartuccio L. Old and new antirheumatic drugs for the treatment of COVID-19. Joint Bone Spine. 2020 May;87(3):195-197. doi: 10.1016/j.jbspin.2020.03.013.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: April 19, 2020): 200
• Original Estimated Enrollment (submitted: March 23, 2020): 60
• Estimated Study Completion Date: July 30, 2020
• Estimated Primary Completion Date: June 30, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT04320277
• Other Study ID Numbers: HPrato-3
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Fabrizio Cantini, Hospital of Prato
• Original Responsible Party: Same as current
• Current Study Sponsor: Hospital of Prato
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Fabrizio Cantini, MD; Hospital of Prato, Italy

• PRS Account: Hospital of Prato
• Verification Date: April 2020