Tofacitinib for Treatment of Moderate COVID-19 (I-TOMIC)
COVID-19 Pneumonia
About this trial
This is an interventional treatment trial for COVID-19 Pneumonia
Eligibility Criteria
Inclusion Criteria:
- Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
- Participants with laboratory-confirmed novel coronavirus (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR) or other commercially available or public health assay prior to Day 1.
- Participants with evidence of pneumonia assessed by radiographic imaging (chest x ray or chest CT scan) AND Requiring ≥ 3L O2 OR ≥ 2L O2 and hsCRP > 70 mg/L
- Participants who are hospitalized and receiving supportive care for COVID-19.
- Participant (or legally authorized representative/surrogate) capable of giving signed informed consent.
Exclusion Criteria:
Medical Conditions:
- Require mechanical ventilation or ECMO on Day 1 at the time of randomization.
- Have current, or history of, venous thromboembolism (deep vein thrombosis or pulmonary embolism).
- Have a personal or first-degree family history of blood clotting disorders.
- Participants who are immunocompromised, with known immunodeficiencies, or taking potent immunosuppressive agents (eg, azathioprine, cyclosporine).
- Participants with any current malignancy or lymphoproliferative disorders that requires active treatment
- Females of child bearing potential who are pregnant or breastfeeding
- Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk associated with study participation or, in the investigator's judgment, make the participant inappropriate for the study.
- Anticipated survival < 72 hours as assessed by the Investigator.
Infection History:
• Suspected or known active systemic bacterial, fungal, or viral infections (with the exception of COVID-19) including but not limited to:
- Secondary bacterial pneumonia;
- Active herpes zoster infection;
- Known active tuberculosis or history of inadequately treated tuberculosis;
- Known HBV, HCV, or HIV.
Prior/Concomitant Therapy:
Have received any of the following treatment regimens specified in the timeframes outlined below:
Within 4 weeks prior to the first dose of study intervention:
- Prior treatment with any JAK inhibitors, potent immunosuppressants, or any biologic agents including IL-6 inhibitors (eg, tocilizumab) or IL-1 inhibitors (eg, anakinra);
- Prior treatment with any potent cytochrome P450 inducer, such as rifampin, within the past 28 days or 5 half-lives, whichever is longer.
Within 48 hours prior to the first dose of study intervention:
o Treatment with herbal supplements.
Received >/= 20 mg/day of prednisone or equivalent for >/=14 consecutive days in the 4 weeks prior to screening.
Diagnostic Assessments:
- Severe hepatic impairment, defined as Child-Pugh class C.
- Severe anemia (hemoglobin <8 g/dL).
- ANY of the following abnormalities in clinical laboratory tests at screening, confirmed by a single repeat, if deemed necessary:
- WBC <1000/mm3
- Absolute lymphocyte count <500 cells/mm3;
- Absolute neutrophil count <1000 cells/mm3.
- Alanine transaminase/aspartate transaminase (ALT/AST) > 5 times the upper limit of normal;
- Estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m2);
Other Exclusions:
- Known allergy to tofacitinib.
- Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
Sites / Locations
- Yale New Haven Health System
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Tofacitinib
Placebo
Tofacitinib will be administered in a dose of 10 mg PO BID until return to their clinical baseline (as defined by supplementary oxygen requirement), and then will continue to be administered at 5 mg PO BID for a total treatment duration of 14 days.
Matching placebo will be administered.