This multi-center, double-blind, placebo-controlled, randomized Phase 2 trial will study the safety, tolerability, and efficacy of bardoxolone methyl in patients hospitalized with confirmed COVID-19. The trial will include approximately 40 patients and is designed to provide an early interim analysis of safety. Patients will be randomized using permuted block randomization in a 1:1 fashion to either once-daily administration of bardoxolone methyl (20 mg) or matching placebo and treatment will be administered for the duration of hospitalization (until recovery), with a maximum treatment duration of 29 days.
Following randomization on Day 1, patients will be assessed while hospitalized on Days 3, 5,
8, 11, 15, 22, and 29. Assessments will include clinical status assessments, vital sign
measurements, clinical chemistry collection, and adverse event collection. Patients that
recover prior to Day 29 will complete an end-of-treatment visit. Patients will have an
in-person follow-up on Day 29, regardless of treatment adherence and recovery status prior to
Day 29, and a safety follow-up 60 days after randomization for clinical status assessments,
vital sign measurements, clinical chemistry collection, and adverse event collection.
Follow-up in-person visits are preferred but recognizing quarantine and other factors may
limit the subject's ability to return to the site for the visit. In this case, the visit may
be performed by phone. An independent Data and Safety Monitoring Board will advise the study
leadership on safety aspects and overall progress of the study.
Drug: Bardoxolone Methyl
Once-daily administration of bardoxolone methyl (20mg)
Drug: Placebo
Once-daily administration of matching placebo
Inclusion Criteria:
1. Laboratory-confirmed COVID-19 infection as determined by polymerase chain reaction
(PCR)
2. Hospitalized patients that meets one of the following conditions:
1. Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.); OR
2. At rest, blood oxygen saturation ≤ 94%; OR
3. Require supplemental oxygen; OR
4. Requiring non-invasive ventilation; OR
5. Requiring invasive mechanical ventilation for up to 2 days.
3. Age ≥ 18 years. Enrollment of patients ≥70 years of age may be limited (e.g., comprise
no more than 10% of all randomized patients), pending safety review by the DSMB and
executive committee
4. Participant or legally authorized representative is willing to give informed consent
Exclusion Criteria:
1. Intubated and on invasive mechanical ventilation for three or more days at the time of
randomization
2. Known left ventricular ejection fraction (LVEF) <40% or prior hospitalization for
heart failure
3. Cardiac arrest
4. Shock
5. Known uncontrolled bacterial, fungal, or non-COVID viral infection
6. eGFR <30 ml/min/1.73 m² or requiring dialysis
7. ALT or AST > 5X ULN
8. History of cirrhosis, chronic active hepatitis or severe hepatic disease
9. Pregnant or lactating women
10. Enrolled in other trial of unapproved therapies, unless approved by trial Principal
Investigator. In general, co-enrollment will be permitted unless there are safety
concerns, mechanistic incompatibility or inability to adjudicate serious adverse
events and will be decided on a case by case basis.
11. If in the opinion of the clinical team, progression to death is imminent and
inevitable within the next 24 hours, irrespective of the provision of treatments
HSHS St. John's Hospital (Prairie Education and Research Cooperative)
Springfield, Illinois, United States
SIU School of Medicine
Springfield, Illinois, United States
NYU Langone Hospital - Brooklyn
Brooklyn, New York, United States
Coney Island Hospital
Brooklyn, New York, United States
Elmhurst Hospital Center
Elmhurst, New York, United States
NYU Winthrop Hospital
Mineola, New York, United States
NYU Bellevue Hospital Center
New York, New York, United States
NYU Langone Health
New York, New York, United States
Sripal Bangalore, MD, MHA, Principal Investigator
NYU Langone Health