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

Sponsor
NYU Langone Health (Other)
Overall Status
Completed
CT.gov ID
NCT04494646
Collaborator
Reata Pharmaceuticals, Inc. (Industry)
40
8
2
4
5
1.2

Study Details

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
  • 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
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 :
Sep 8, 2020
Actual Primary Completion Date :
Jan 8, 2021
Actual Study Completion Date :
Jan 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. Number of Serious Adverse Events [Day 29]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
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:

  3. Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.); OR

  4. At rest, blood oxygen saturation ≤ 94%; OR

  5. Require supplemental oxygen; OR

  6. Requiring non-invasive ventilation; OR

  7. Requiring invasive mechanical ventilation for up to 2 days.

  8. 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

  9. 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

Site City State Country Postal Code
1 HSHS St. John's Hospital (Prairie Education and Research Cooperative) Springfield Illinois United States 62769
2 SIU School of Medicine Springfield Illinois United States 62794
3 NYU Langone Hospital - Brooklyn Brooklyn New York United States 11220
4 Coney Island Hospital Brooklyn New York United States 11235
5 Elmhurst Hospital Center Elmhurst New York United States 11373
6 NYU Winthrop Hospital Mineola New York United States 11501
7 NYU Bellevue Hospital Center New York New York United States 10016
8 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

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
NYU Langone Health
ClinicalTrials.gov Identifier:
NCT04494646
Other Study ID Numbers:
  • 20-00591
First Posted:
Jul 31, 2020
Last Update Posted:
Jan 13, 2022
Last Verified:
Jan 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by NYU Langone Health
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Bardoxolone Methyl Placebo
Arm/Group Description 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) 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
Period Title: Overall Study
STARTED 21 19
COMPLETED 21 17
NOT COMPLETED 0 2

Baseline Characteristics

Arm/Group Title Bardoxolone Methyl Placebo Total
Arm/Group Description 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) 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 Total of all reporting groups
Overall Participants 21 17 38
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
57.3
(16.3)
60.5
(12.5)
57.4
(14.2)
Sex: Female, Male (Count of Participants)
Female
9
42.9%
5
29.4%
14
36.8%
Male
12
57.1%
12
70.6%
24
63.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
5
23.8%
6
35.3%
11
28.9%
Not Hispanic or Latino
16
76.2%
11
64.7%
27
71.1%
Unknown or Not Reported
0
0%
0
0%
0
0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
1
5.9%
1
2.6%
Asian
1
4.8%
1
5.9%
2
5.3%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
1
4.8%
3
17.6%
4
10.5%
White
16
76.2%
9
52.9%
25
65.8%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
3
14.3%
3
17.6%
6
15.8%
Region of Enrollment (participants) [Number]
United States
21
100%
17
100%
38
100%

Outcome Measures

1. Primary Outcome
Title Number of Serious Adverse Events
Description
Time Frame Day 29

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Bardoxolone Methyl Placebo
Arm/Group Description 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) 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
Measure Participants 21 17
Number [Adverse Events]
4
6

Adverse Events

Time Frame 29 Days
Adverse Event Reporting Description
Arm/Group Title Bardoxolone Methyl Placebo
Arm/Group Description 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) 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
All Cause Mortality
Bardoxolone Methyl Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/21 (0%) 4/17 (23.5%)
Serious Adverse Events
Bardoxolone Methyl Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 4/21 (19%) 6/17 (35.3%)
Cardiac disorders
Cardiac failure acute, Acute on chronic systolic (congestive) heart failure 0/21 (0%) 1/17 (5.9%)
Ventricular tachycardia 0/21 (0%) 1/17 (5.9%)
Infections and infestations
Pneumonia due to covid-19 virus 1/21 (4.8%) 0/17 (0%)
Injury, poisoning and procedural complications
Splenic rupture 1/21 (4.8%) 0/17 (0%)
Abdominal wall wound, Worsening abdominal wound 1/21 (4.8%) 0/17 (0%)
Splenic laceration 1/21 (4.8%) 0/17 (0%)
Nervous system disorders
Presyncope, Pre-syncope 0/21 (0%) 1/17 (5.9%)
Renal and urinary disorders
Nephrolithiasis, Nephrolithiasis 1/21 (4.8%) 0/17 (0%)
Respiratory, thoracic and mediastinal disorders
Hypoxia, Worsening hypoxia 0/21 (0%) 1/17 (5.9%)
Respiratory failure Worsening hypoxemic respiratory failure 0/21 (0%) 1/17 (5.9%)
Pulmonary Embolism 0/21 (0%) 1/17 (5.9%)
Surgical and medical procedures
Mechanical ventilation, Invasive mechanical ventilation 1/21 (4.8%) 0/17 (0%)
Mechanical ventilation 0/21 (0%) 1/17 (5.9%)
Other (Not Including Serious) Adverse Events
Bardoxolone Methyl Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/21 (4.8%) 1/17 (5.9%)
Infections and infestations
Fungal Infection 0/21 (0%) 1/17 (5.9%)
Nervous system disorders
Dizziness and Lightheadedness 1/21 (4.8%) 0/17 (0%)
Loss of Consciousness 1/21 (4.8%) 0/17 (0%)
Blackouts 1/21 (4.8%) 0/17 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Sripal Bangalore, MD, MHA
Organization NYU Langone Health
Phone (212) 263 3540
Email Sripal.Bangalore@nyulangone.org
Responsible Party:
NYU Langone Health
ClinicalTrials.gov Identifier:
NCT04494646
Other Study ID Numbers:
  • 20-00591
First Posted:
Jul 31, 2020
Last Update Posted:
Jan 13, 2022
Last Verified:
Jan 1, 2022