Covid19
Conditions
Keywords
Bardoxolone Methyl
Brief summary
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.
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.
Interventions
Once-daily administration of bardoxolone methyl (20mg)
DRUGPlacebo
Once-daily administration of matching placebo
Sponsors
Reata Pharmaceuticals, Inc.
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, 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).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Serious Adverse Events | Day 29 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
Bardoxolone Methyl: Once-daily administration of bardoxolone methyl (20mg) | 21 |
| 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
Placebo: Once-daily administration of matching placebo | 17 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Bardoxolone Methyl | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 57.3 years STANDARD_DEVIATION 16.3 | 57.4 years STANDARD_DEVIATION 14.2 | 60.5 years STANDARD_DEVIATION 12.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 11 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 27 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) White | 16 Participants | 25 Participants | 9 Participants |
| Region of Enrollment United States | 21 participants | 38 participants | 17 participants |
| Sex: Female, Male Female | 9 Participants | 14 Participants | 5 Participants |
| Sex: Female, Male Male | 12 Participants | 24 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 4 / 17 |
| other Total, other adverse events | 1 / 21 | 1 / 17 |
| serious Total, serious adverse events | 4 / 21 | 6 / 17 |
Outcome results
Primary
Number of Serious Adverse Events
Time frame: Day 29
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bardoxolone Methyl | Number of Serious Adverse Events | 4 Adverse Events |
| Placebo | Number of Serious Adverse Events | 6 Adverse Events |