Tofacitinib for Treatment of Moderate COVID-19

• Status: Terminated
• Trial end date: 2021-02-28
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this randomized, double blinded, placebo controlled study is to assess the efficacy and safety of tofacitinib in hospitalized adult (18-99 years old) patients with SARS-CoV-2 and pneumonia who require supplemental oxygen and have serologic markers of inflammation but do not need mechanical ventilation.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Yale University
• Treatments: Tofacitinib

Criteria

Inclusion Criteria:

1. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

2. 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.

3. 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

4. Participants who are hospitalized and receiving supportive care for COVID-19.

5. Participant (or legally authorized representative/surrogate) capable of giving signed informed consent.

Exclusion Criteria:

Medical Conditions:

1. Require mechanical ventilation or ECMO on Day 1 at the time of randomization.

2. Have current, or history of, venous thromboembolism (deep vein thrombosis or pulmonary embolism).

3. Have a personal or first-degree family history of blood clotting disorders.

4. Participants who are immunocompromised, with known immunodeficiencies, or taking potent immunosuppressive agents (eg, azathioprine, cyclosporine).

5. Participants with any current malignancy or lymphoproliferative disorders that requires active treatment

6. Females of child bearing potential who are pregnant or breastfeeding

7. 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.

8. 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.