NCT04469114

Tofacitinib in Hospitalized Patients With COVID-19 Pneumonia

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-design Trial of Tofacitinib in Hospitalized Participants With COVID-19 Pneumonia

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 289 (actual)
• Sponsor: Hospital Israelita Albert Einstein · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Tofacitinib suppresses pro-inflammatory signaling that may be important pathogenetically to progression to more severe lung disease and acute respiratory distress syndrome (ARDS) in patients with COVID-19. The purpose of the study is to assess the safety and efficacy of tofacitinib plus standard pharmacologic and supportive measures in treating hospitalized participants with COVID-19 pneumonia.

Detailed description

COVID-19 is a viral disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that can cause severe pneumonia and ARDS. Respiratory viral load may peak within 5 days after onset, while symptoms are still mild. Many patients rapidly (within 1 to 2 weeks of infection) develop dyspnea and pneumonia and require hospitalization for respiratory support. Preliminary clinical data from COVID-19 patients indicate that severe symptoms with SARS-CoV-2 infection are associated with an exaggerated immune response driven by interleukin (IL)-6 IL-10, tumor necrosis factor (TNF)α, and other cytokines. The ultimate result is progressive destruction of the alveolar epithelium leading to pneumonia and/or ARDS. Moreover, the exudative phase of ARDS is thought to be due to an influx of myeloid cells (neutrophils and macrophages) and elevations of inflammatory cytokines, with higher levels of both IL-6 and IL-8 levels being correlated with increased mortality. Therefore, immunomodulatory therapy may be beneficial in reducing the deleterious effects of lung inflammation and mitigating progressive lung injury. Tofacitinib is an inhibitor of Janus kinase (JAKs) 1 and 3, with partial selectivity to JAK 2. Tofacitinib suppresses pro-inflammatory signaling that may be important pathogenetically to progression to more severe lung disease and ARDS in patients with COVID-19. The purpose of the study is to assess the safety and efficacy of tofacitinib plus standard pharmacologic and supportive measures in treating hospitalized participants with COVID-19 pneumonia. Participants with laboratory confirmed SARS-CoV-2 infection as determined by a positive PCR, who have agreed to participate, will be screened within 72h hours after admission to the hospital to determine eligibility. Eligible participants will be randomized on Day 1 to the tofacitinib plus standard of care treatment group or the placebo plus standard of care treatment group in a 1:1 ratio, stratified by site. Participants will receive treatment for up to 14 days or until discharge from the hospital, whichever is earlier. Participants will be assessed daily (up to Day 28) while hospitalized for clinical, safety, and laboratory parameters. Follow-up visits will occur on Day 14 and on Day 28.

Conditions

• Covid19

Interventions

Type	Name	Description
DRUG	Tofacitinib 10 mg	Tofacitinib 10mg administered orally twice daily for 14 days or until hospital discharge
DRUG	Placebo	Tofacitinib-matching placebo administered orally twice daily for 14 days or until hospital discharge

Timeline

• Start date: 2020-09-16
• Primary completion: 2021-01-09
• Completion: 2021-01-09
• First posted: 2020-07-13
• Last updated: 2021-08-09

Locations

17 sites across 1 country: Brazil

Regulatory

• FDA-regulated drug study