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

BARCONA: A Phase II, Randomized, Double-blind, Placebo-controlled, Multi-center Study of the Effects of Bardoxolone Methyl in Participants With SARS-Corona Virus-2 (COVID-19)

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: Bardoxolone Methyl; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Springfield, Illinois, United States, 62769
      • HSHS St. John's Hospital (Prairie Education and Research Cooperative)
    • Springfield, Illinois, United States, 62794
      • SIU School of Medicine
  • New York
    • Brooklyn, New York, United States, 11235
      • Coney Island Hospital
    • Brooklyn, New York, United States, 11220
      • NYU Langone Hospital - Brooklyn
    • Elmhurst, New York, United States, 11373
      • Elmhurst Hospital Center
    • Mineola, New York, United States, 11501
      • NYU Winthrop Hospital
    • New York, New York, United States, 10016
      • NYU Langone Health
    • New York, New York, United States, 10016
      • NYU Bellevue Hospital Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Serious Adverse Events	Day 29

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: Reata Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Sripal Bangalore, MD, MHA, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2020
• Primary Completion (Actual): January 8, 2021
• Study Completion (Actual): January 8, 2021

Study Registration Dates

• First Submitted: July 29, 2020
• First Submitted That Met QC Criteria: July 29, 2020
• First Posted (Actual): July 31, 2020

Study Record Updates

• Last Update Posted (Actual): January 13, 2022
• Last Update Submitted That Met QC Criteria: January 11, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Bardoxolone Methyl
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections
• Other Study ID Numbers: 20-00591

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices) will be shared upon reasonable request.
• IPD Sharing Time Frame: Data will become available beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data will have access to the data upon reasonable request. Requests should be directed to Sripal.Bangalore@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No