Safety and Efficacy of Tofacitinib in Hospitalized Participants With COVID-19 Pneumonia Who Are Receiving Standard of Care Therapy

A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY ASSESSING THE SAFETY AND EFFICACY OF TOFACITINIB IN HOSPITALIZED PARTICIPANTS WITH COVID-19 PNEUMONIA WHO ARE RECEIVING STANDARD OF CARE THERAPY

The study is designed as a multicenter, randomized, double-blind, placebo-controlled, parallel group study of the safety and efficacy of tofacitinib in hospitalized adult participants with COVID-19 pneumonia who are receiving SoC therapy and who are not on HFNC, noninvasive ventilation, invasive mechanical ventilation, or ECMO on Day 1 at the time of randomization.

Participants with laboratory confirmed SARS-CoV-2 infection as determined by a positive PCR or other commercially available or public health assay, who have agreed to participate will be screened within 48 hours after hospitalization to determine eligibility. This should be completed within 48 hours prior to Day 1.

Eligible participants will be randomized on Day 1 in a 1:1 ratio to the tofacitinib treatment group or the placebo treatment group and will receive treatment for up to 14 days, or until discharge from the hospital, whichever is earlier. If a participant requires intubation prior to the end of the 14-day treatment period, they will continue to receive tofacitinib or matching placebo until Day 14 (or until discharge from the hospital, if earlier than Day 14), if clinically appropriate.

Participants will be assessed daily (up to Day 28) while hospitalized for clinical, safety, and laboratory parameters. Follow-up visits will occur on Day 28, 28 to 35 days after the ET/ED/EOT visit, and on Day 60.

An independent, external DSMB will be convened to oversee the safety of participants and make recommendations regarding the conduct of the trial in accordance with the Charter.

Study Overview

• Status: Withdrawn
• Conditions: COVID-19
• Intervention / Treatment: Drug: Tofacitinib; Other: Placebo

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital (HH)
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals & Clinics Investigational Drug Services
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • LSUHSC-Shreveport
    • Shreveport, Louisiana, United States, 71103
      • Ochsner LSU Health Shreveport Academic Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female between 18 and 65 years. A female is eligible if she is not pregnant or breastfeeding. WOCBP must use 2 highly effective forms of contraception.
• Participants with laboratory-confirmed novel coronavirus (SARS-CoV-2) infection prior to Day 1.
• Participants with evidence of COVID-19 pneumonia assessed by radiographic imaging (chest x ray or chest CT scan).

Exclusion Criteria:

• Require HFNC, non-invasive ventilation, invasive mechanical ventilation, or ECMO on Day 1 at the time of randomization.
• Have history of or current thrombosis. Only if current thrombosis is suspected, imaging testing is recommended (e.g. CTPA or per local guidance) to exclude thrombosis.
• Have a personal or first degree family history of blood clotting disorders.
• Participants who are immunocompromised, with known immunodeficiencies, or taking potent immunosuppressive agents (e.g. azathioprine, cyclosporine).
• Participants with any current malignancy or lymphoproliferative disorders that requires active treatment.
• Suspected or known active systemic bacterial, fungal, or viral infections (with the exception of COVID-19).
• Severe hepatic impairment, defined as Child-Pugh class C.
• Severe anemia (hemoglobin < 8 g/dL)
• ANY of the following abnormalities in clinical lab tests at screening, confirmed by a single repeat, if deemed necessary: ALC < 500 cells/mm3, ANC < 1000 cells/mm3
• Known allergy to tofacitinib

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tofacitinib; Participants will receive tofacitinib 10 mg twice per day for 14 days and standard of care therapy.	Drug: Tofacitinib; 10 mg tofacitinib administered as two 5 mg tablets or solution taken orally twice daily for 14 days; Other Names: xeljanz
Placebo Comparator: Placebo; Participants will receive tofacitinib-matching placebo twice per day for 14 days and standard of care therapy.	Other: Placebo; Tofacitinib-matching placebo administered as tablets or solution taken orally twice daily for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical status using ordinal scale	Death or respiratory failure (1, 2, or 3, on an 8-point ordinal scale of disease severity) at Day 28. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical status using ordinal scale	Ordinal scale of disease severity. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.	Day 14
Status of alive and not using mechanical ventilation or extracorporeal membrane oxygenation (ECMO)	Category 3 to 8 on an ordinal scale of disease severity. The scale is as follows: 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.	Day 14 and Day 28
Status of discharged or not requiring supplemental oxygen	Category 5 to 8 on an ordinal scale of disease severity. The scale is as follows: 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.	Day 28
Mortality	Category 1 on an ordinal scale of disease severity. The scale is as follows: 1) Death.	Day 60

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 6, 2020
• Primary Completion (Anticipated): September 16, 2020
• Study Completion (Anticipated): October 18, 2020

Study Registration Dates

• First Submitted: May 30, 2020
• First Submitted That Met QC Criteria: May 30, 2020
• First Posted (Actual): June 2, 2020

Study Record Updates

• Last Update Posted (Actual): July 31, 2020
• Last Update Submitted That Met QC Criteria: July 29, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Pneumonia; COVID-19; Novel Coronavirus
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: A3921377

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No