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

• ClinicalTrials.gov Identifier: NCT04412252
• Recruitment Status: Withdrawn
• First Posted: June 2, 2020
• Last Update Posted: July 31, 2020
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: May 30, 2020
• First Posted Date: June 2, 2020
• Last Update Posted Date: July 31, 2020
• Estimated Study Start Date: July 6, 2020
• Estimated Primary Completion Date: September 16, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 30, 2020)

Clinical status using ordinal scale [ Time Frame: Day 28 ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 8, 2020)

• Clinical status using ordinal scale [ Time Frame: Day 14 ]
  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.
• Status of alive and not using mechanical ventilation or extracorporeal membrane oxygenation (ECMO) [ Time Frame: Day 14 and Day 28 ]
  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.
• Status of discharged or not requiring supplemental oxygen [ Time Frame: Day 28 ]
  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.
• Mortality [ Time Frame: Day 60 ]
  Category 1 on an ordinal scale of disease severity. The scale is as follows: 1) Death.

Original Secondary Outcome Measures (submitted: May 30, 2020)

• Clinical status using ordinal scale [ Time Frame: Day 14 ]
  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.
• Status of alive and not using mechanical ventilation or extracorporeal membrane oxygenation (ECMO) [ Time Frame: Day 14 and Day 28 ]
  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.
• Status of discharged or not requiring supplemental oxygen [ Time Frame: Day 28 ]
  Category 5 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.
• Mortality [ Time Frame: Day 60 ]
  Category 1 on an ordinal scale of disease severity. The scale is as follows: 1) Death.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of Tofacitinib in Hospitalized Participants With COVID-19 Pneumonia Who Are Receiving Standard of Care Therapy
• Official Title: 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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: COVID-19

Intervention

• Drug: Tofacitinib
  10 mg tofacitinib administered as two 5 mg tablets or solution taken orally twice daily for 14 days
  Other Name: xeljanz
• Other: Placebo
  Tofacitinib-matching placebo administered as tablets or solution taken orally twice daily for 14 days

Study Arms

• Experimental: Tofacitinib
  Participants will receive tofacitinib 10 mg twice per day for 14 days and standard of care therapy.
  Intervention: Drug: Tofacitinib
• Placebo Comparator: Placebo
  Participants will receive tofacitinib-matching placebo twice per day for 14 days and standard of care therapy.
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: July 29, 2020): 0
• Original Estimated Enrollment (submitted: May 30, 2020): 265
• Estimated Study Completion Date: October 18, 2020
• Estimated Primary Completion Date: September 16, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04412252
• Other Study ID Numbers: A3921377
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: July 2020