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

• ClinicalTrials.gov Identifier: NCT04494646
• Recruitment Status: Completed
• First Posted: July 31, 2020
• Last Update Posted: February 24, 2021
• Sponsor: NYU Langone Health
• Collaborator: Reata Pharmaceuticals, Inc.
• Information provided by (Responsible Party): NYU Langone Health

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Covid19	Drug: Bardoxolone Methyl; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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).
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: September 8, 2020
• Actual Primary Completion Date: January 8, 2021
• Actual Study Completion Date: January 8, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Incidence of Serious Adverse Events [ Time Frame: Day 29 ]

Secondary Outcome Measures :

1. Average number of renal replacement therapy (RRT)-free days [ Time Frame: Day 29 ]
2. Average number of mechanical ventilation-free days [ Time Frame: Day 29 ]
3. Incidence of All-Cause Mortality [ Time Frame: Day 29 ]
4. Proportion of participants who experienced deterioration from baseline [ Time Frame: Day 29 ]

   Deterioration is defined by a 1-point worsening scale:

   0- Uninfected; no viral RNA detected, 1- Asymptomatic; viral RNA detected, 2- Symptomatic; Independent, 3- Symptomatic; assistance needed, 4- Hospitalized; no oxygen therapy, 5- Hospitalized; oxygen by mask or nasal prongs, 6- Hospitalized; oxygen by NIV or High flow, 7- Intubation & Mechanical ventilation; pO2/FIO2 >/= 150 or SpO2/FIO2 >/=200, 8- Mechanical ventilation pO2/FIO2 < 150 (SpO2/FIO2 <200) or vasopressors, 9- Mechanical ventilation pO2/FIO2 < 150 and vasopressors, dialysis or ECMO, 10- Death

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Illinois

HSHS St. John's Hospital (Prairie Education and Research Cooperative)

Springfield, Illinois, United States, 62769

SIU School of Medicine

Springfield, Illinois, United States, 62794

United States, New York

NYU Langone Hospital - Brooklyn

Brooklyn, New York, United States, 11220

Coney Island Hospital

Brooklyn, New York, United States, 11235

Elmhurst Hospital Center

Elmhurst, New York, United States, 11373

NYU Winthrop Hospital

Mineola, New York, United States, 11501

NYU Bellevue Hospital Center

New York, New York, United States, 10016

NYU Langone Health

New York, New York, United States, 10016

Sponsors and Collaborators

NYU Langone Health

Reata Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Sripal Bangalore, MD, MHA; NYU Langone Health

More Information

• Responsible Party: NYU Langone Health
• ClinicalTrials.gov Identifier: NCT04494646
• Other Study ID Numbers: 20-00591
• First Posted: July 31, 2020
• Last Update Posted: February 24, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• 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.
• 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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by NYU Langone Health:

Bardoxolone Methyl

Additional relevant MeSH terms:

Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases