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.
The purpose of this randomized, double blinded, placebo controlled Phase 2b study is to
assess the efficacy and safety of tofacitinib in hospitalized adult (18-99 years old) male
and female patients with SARS-CoV-2 and pneumonia who require supplemental oxygen and have
serologic markers of inflammation but do not need mechanical ventilation (see Inclusion
criteria). Sixty patients will be recruited to receive tofacitinib or placebo in addition to
standard of care (SOC) in a 1:1 ratio.
Subjects will be screened during hospitalization. Patients with confirmed SARS-CoV-2
infection, and meeting all other Inclusion and Exclusion criteria, will be randomized to
either treatment with tofacitinib or placebo in addition to SOC during hospitalization (dose
adjusted, if required), with the exception of pre-specified immunomodulatory agents (as
documented in the inclusion/exclusion criteria). Tofacitinib will be administered in a dose
of 10 mg PO BID until return to their clinical baseline (as defined by need for supplementary
oxygen), and will continue to be administered at 5 mg PO BID for a total duration of therapy
of 14 days; follow-up off tofacitinib will continue up to Day 90. We anticipate completion of
subject recruitment in 6 months.
Drug: Tofacitinib 10 mg
Tofacitinib will be administered in a dose of 10 mg twice daily by mouth (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.
Drug: Placebo
Matching placebo tablets will be administered.
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.
Yale New Haven Health System
New Haven, Connecticut, United States
Hyung Chun, MD, Principal Investigator
Yale School of Medicine