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

Sponsor

Pfizer (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT04412252

Collaborator

(none)

Enrollment

Locations

Arms

3.4

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Tofacitinib Other: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jul 6, 2020

Anticipated Primary Completion Date :

Sep 16, 2020

Anticipated Study Completion Date :

Oct 18, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Clinical status using ordinal scale [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.

Secondary Outcome Measures

Clinical status using ordinal scale [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) [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 [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 [Day 60]
Category 1 on an ordinal scale of disease severity. The scale is as follows: 1) Death.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hartford Hospital (HH)	Hartford	Connecticut	United States	06102
2	University of Iowa Hospitals & Clinics Investigational Drug Services	Iowa City	Iowa	United States	52242
3	University of Iowa	Iowa City	Iowa	United States	52242
4	LSUHSC-Shreveport	Shreveport	Louisiana	United States	71103
5	Ochsner LSU Health Shreveport Academic Medical Center	Shreveport	Louisiana	United States	71103
6	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106