Safety and Efficacy of Tofacitinib in Hospitalized Participants With COVID-19 Pneumonia Who Are Receiving Standard of Care Therapy
Primary Purpose
COVID-19
Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tofacitinib
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring COVID-19, Pneumonia, SARS-CoV-2, Novel Coronavirus
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
Sites / Locations
- Hartford Hospital (HH)
- University of Iowa Hospitals & Clinics Investigational Drug Services
- University of Iowa
- LSUHSC-Shreveport
- Ochsner LSU Health Shreveport Academic Medical Center
- University Hospitals Cleveland Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Tofacitinib
Placebo
Arm Description
Participants will receive tofacitinib 10 mg twice per day for 14 days and standard of care therapy.
Participants will receive tofacitinib-matching placebo twice per day for 14 days and standard of care therapy.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
Mortality
Category 1 on an ordinal scale of disease severity. The scale is as follows: 1) Death.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04412252
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Due to the pursuit of other SARS-CoV-2-related research including alternative trials with tofacitinib, this trial was canceled prior to subject enrollment.
Study Start Date
July 6, 2020 (Anticipated)
Primary Completion Date
September 16, 2020 (Anticipated)
Study Completion Date
October 18, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
COVID-19, Pneumonia, SARS-CoV-2, Novel Coronavirus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tofacitinib
Arm Type
Experimental
Arm Description
Participants will receive tofacitinib 10 mg twice per day for 14 days and standard of care therapy.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive tofacitinib-matching placebo twice per day for 14 days and standard of care therapy.
Intervention Type
Drug
Intervention Name(s)
Tofacitinib
Other Intervention Name(s)
xeljanz
Intervention Description
10 mg tofacitinib administered as two 5 mg tablets or solution taken orally twice daily for 14 days
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Tofacitinib-matching placebo administered as tablets or solution taken orally twice daily for 14 days
Primary Outcome Measure Information:
Title
Clinical status using ordinal scale
Description
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.
Time Frame
Day 28
Secondary Outcome Measure Information:
Title
Clinical status using ordinal scale
Description
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.
Time Frame
Day 14
Title
Status of alive and not using mechanical ventilation or extracorporeal membrane oxygenation (ECMO)
Description
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.
Time Frame
Day 14 and Day 28
Title
Status of discharged or not requiring supplemental oxygen
Description
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.
Time Frame
Day 28
Title
Mortality
Description
Category 1 on an ordinal scale of disease severity. The scale is as follows: 1) Death.
Time Frame
Day 60
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Hartford Hospital (HH)
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06102
Country
United States
Facility Name
University of Iowa Hospitals & Clinics Investigational Drug Services
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
LSUHSC-Shreveport
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States
Facility Name
Ochsner LSU Health Shreveport Academic Medical Center
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States
Facility Name
University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=A3921377
Description
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Learn more about this trial
Safety and Efficacy of Tofacitinib in Hospitalized Participants With COVID-19 Pneumonia Who Are Receiving Standard of Care Therapy
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