Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)
Masking Description
All patients, investigators, site personnel, laboratories, and study personnel with direct involvement in the conduct of the study or their designees will be blinded to treatment assignments. To prevent potential bias, appropriate measures will be taken to ensure the blind is maintained for the patients and personnel mentioned previously. To maintain the blind, investigators will distribute blinded study drug treatment to patients as directed by the IWRS system. Investigators and patients will not be blinded to dose level, but will be blinded to treatment assignment (i.e., bardoxolone methyl vs. placebo).

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Bardoxolone Methyl
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
  • Drug: Bardoxolone Methyl
    Once-daily administration of bardoxolone methyl (20mg)
Placebo Comparator
Placebo
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
  • Drug: Placebo
    Once-daily administration of matching placebo

Recruiting Locations

More Details

NCT ID
NCT04494646
Status
Completed
Sponsor
NYU Langone Health

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.