BARCONA: A Study of Effects of Bardoxolone Methyl in Participants With SARS-Corona Virus-2 (COVID-19)

Phase 2

Completed

• Conditions: Covid19
• Interventions: Drug: Bardoxolone Methyl; Drug: Placebo

• Registration Number: NCT04494646
• Lead Sponsor: NYU Langone Health

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.

Study Timeline

• Study First Submitted: 2020-07-29
• Study First Submitted QC: 2020-07-29
• Study First Posted: 2020-07-31
• Study Start: 2020-09-08
• Primary Completion: 2021-01-08
• Study Completion: 2021-01-08
• Status Verified: 2022-01
• Results First Submitted: 2022-01-07
• Results First Submitted QC: 2022-01-07
• Last Update Submitted: 2022-01-11
• Results First Posted: 2022-01-12
• Last Update Posted: 2022-01-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bardoxolone Methyl	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
Placebo	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

Primary Outcome Measures

Name	Time	Method
Number of Serious Adverse Events	Day 29

Trial Locations

Locations (8)

NYU Winthrop Hospital; 🇺🇸 Mineola, New York, United States

NYU Langone Health; 🇺🇸 New York, New York, United States

HSHS St. John's Hospital (Prairie Education and Research Cooperative); 🇺🇸 Springfield, Illinois, United States

SIU School of Medicine; 🇺🇸 Springfield, Illinois, United States

NYU Bellevue Hospital Center; 🇺🇸 New York, New York, 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