Bardoxolone Methyl Evaluation in Patients With Pulmonary Hypertension (PH) - LARIAT

NCT02036970 | Completed Phase 2 Results DMC

• 1 other identifier: RTA 402-C-1302
• Study Type: interventional
• Target: 166
• Locations: 2 countries
• Sites: 32

Brief Summary

This study assesses the safety and efficacy of bardoxolone methyl relative to placebo in patients with pulmonary hypertension to determine the recommended dose range, evaluate the change from baseline in 6-minute walk distance (6MWD) and determine the effect of Bardoxolone methyl in pulmonary hypertension associated with connective tissue disease, interstitial lung disease, and idiopathic etiologies, including subsets of patients with WHO Group III or WHO Group V PH following 16 weeks of study participation.

Conditions

Pulmonary Arterial Hypertension; Pulmonary Hypertension; Interstitial Lung Disease; Idiopathic Interstitial Pneumonia; Idiopathic Pulmonary Fibrosis; Sarcoidosis; Respiratory Bronchiolitis Associated Interstitial Lung Disease; Desquamative Interstitial Pneumonia; Cryptogenic Organizing Pneumonia; Acute Interstitial Pneumonitis; Idiopathic Lymphoid Interstitial Pneumonia; Idiopathic Pleuroparenchymal Fibroelastosis

Keywords

Pulmonary Arterial Hypertension; PAH; Bardoxolone methyl; 6-minute walk distance; CDDO-me; RTA 402; Pulmonary Hypertension; Interstitial Lung Disease; Idiopathic Interstitial Pneumonia; Idiopathic Pulmonary Fibrosis; Sarcoidosis; Respiratory Bronchiolitis Associated ILD; Desquamative Interstitial Pneumonia; Cryptogenic Organizing Pneumonia; Acute Interstitial Pneumonitis; Idiopathic Lymphoid Interstitial Pneumonia; Idiopathic Pleuroparenchymal Fibroelastosis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline Though Week 16 in 6-Minute Walk Distance (6MWD) for Bardoxolone Methyl Compared to Placebo

  Overall treatment effect in exercise capacity, as measured by the total distance walked in 6 minutes (6MWD) mean change from baseline though Week 16. A lower 6MWD reflects greater severity thus, a positive change from baseline suggests an improvement.

  Baseline through Week 16

Study Arms (10)

Part 1 Dose-Ranging Bardoxolone methyl 2.5 mg/Part 2: Open-Label

EXPERIMENTAL

Participants received bardoxolone methyl 2.5 mg once-daily in Part 1 (Day 1 to Week 16). Participants who continued to Part 2 continued to receive the same bardoxolone methyl 2.5 mg once-daily in Part 2 (Week 16 and onwards)

Drug: Bardoxolone methyl

Part 1: Dose-Ranging Bardoxolone methyl 5 mg/Part 2: Open-Label

EXPERIMENTAL

Participants received bardoxolone methyl 5 mg once-daily in Part 1 (Day 1 to Week 16). Participants who continued to Part 2 continued to receive the same bardoxolone methyl 5 mg once-daily in Part 2 (Week 16 and onwards)

Drug: Bardoxolone methyl

Part 1: Dose-Ranging Bardoxolone methyl 10 mg/Part 2: Open-Label

EXPERIMENTAL

Participants received bardoxolone methyl 10 mg once-daily in Part 1 (Day 1 to Week 16). Participants who continued to Part 2 continued to receive the same bardoxolone methyl 10 mg once-daily in Part 2 (Week 16 and onwards)

Drug: Bardoxolone methyl

Part 1: Dose-Ranging Bardoxolone methyl 20 mg/Part 2: Open-Label

EXPERIMENTAL

Participants received bardoxolone methyl 20 mg once-daily in Part 1 (Day 1 to Week 16). Participants who continued to Part 2 continued to receive the same bardoxolone methyl 20 mg once-daily in Part 2 (Week 16 and onwards)

Drug: Bardoxolone methyl

Part 1: Dose-Ranging Placebo 2.5 mg/Part 2: Bardoxolone methyl 2.5 mg

PLACEBO COMPARATOR

Participants received bardoxolone methyl 2.5 mg matching placebo capsules once-daily in Part 1 (Day 1 to Week 16). Participants who continued to Part 2 received bardoxolone methyl 2.5 mg once-daily in Part 2 (Week 16 and onwards)

Drug: Bardoxolone methyl; Drug: Placebo

Part 1: Dose-Ranging Placebo 5 mg/Part 2: Bardoxolone methyl 5 mg

PLACEBO COMPARATOR

Participants received bardoxolone methyl 5 mg matching placebo capsules once-daily in Part 1 (Day 1 to Week 16). Participants who continued to Part 2 received bardoxolone methyl 5 mg once-daily in Part 2 (Week 16 and onwards)

Drug: Bardoxolone methyl; Drug: Placebo

Part 1: Dose-Ranging Placebo 10 mg/Part 2: Bardoxolone methyl 10 mg

PLACEBO COMPARATOR

Participants received bardoxolone methyl 10 mg matching placebo capsules once-daily in Part 1 (Day 1 to Week 16). Participants who continued to Part 2 received bardoxolone methyl 10 mg once-daily in Part 2 (Week 16 and onwards)

Drug: Bardoxolone methyl; Drug: Placebo

Part 1: Dose-Ranging Placebo 20 mg/Part 2: Bardoxolone methyl 20 mg

PLACEBO COMPARATOR

Participants received bardoxolone methyl 20 mg matching placebo capsules once-daily in Part 1 (Day 1 to Week 16). Participants who continued to Part 2 received bardoxolone methyl 20 mg once-daily in Part 2 (Week 16 and onwards)

Drug: Bardoxolone methyl; Drug: Placebo

Part 1: Dose Titration: Bardoxolone methyl 10 mg/Part 2: Bardoxolone methyl 10 mg

EXPERIMENTAL

Participants in Part 1 started with bardoxolone methyl 5 mg once-daily from Day 1 and escalated to bardoxolone methyl 10 mg once-daily starting at Week 4 thru Week 16. Participants who continued to Part 2 continued to receive the same bardoxolone methyl dose once-daily in Part 2 (Week 16 and onwards)

Drug: Bardoxolone methyl

Part 1: Dose Titration: Placebo 10 mg/Part 2: Bardoxolone methyl 10 mg

PLACEBO COMPARATOR

Participants in Part 1 received Placebo once-daily from Day 1 thru Week 16. Participants who continued to Part 2 initially received bardoxolone methyl 5 mg once-daily from Week 16 thru Week 20 and bardoxolone methyl 10 mg from week 20 onwards

Drug: Bardoxolone methyl; Drug: Placebo

Interventions

Bardoxolone methyl DRUG

Also known as: RTA 402 capsules

Part 1 Dose-Ranging Bardoxolone methyl 2.5 mg/Part 2: Open-Label; Part 1: Dose Titration: Bardoxolone methyl 10 mg/Part 2: Bardoxolone methyl 10 mg; Part 1: Dose Titration: Placebo 10 mg/Part 2: Bardoxolone methyl 10 mg; Part 1: Dose-Ranging Bardoxolone methyl 10 mg/Part 2: Open-Label; Part 1: Dose-Ranging Bardoxolone methyl 20 mg/Part 2: Open-Label; Part 1: Dose-Ranging Bardoxolone methyl 5 mg/Part 2: Open-Label; Part 1: Dose-Ranging Placebo 10 mg/Part 2: Bardoxolone methyl 10 mg; Part 1: Dose-Ranging Placebo 2.5 mg/Part 2: Bardoxolone methyl 2.5 mg; Part 1: Dose-Ranging Placebo 20 mg/Part 2: Bardoxolone methyl 20 mg; Part 1: Dose-Ranging Placebo 5 mg/Part 2: Bardoxolone methyl 5 mg

Placebo DRUG

Part 1: Dose Titration: Placebo 10 mg/Part 2: Bardoxolone methyl 10 mg; Part 1: Dose-Ranging Placebo 10 mg/Part 2: Bardoxolone methyl 10 mg; Part 1: Dose-Ranging Placebo 2.5 mg/Part 2: Bardoxolone methyl 2.5 mg; Part 1: Dose-Ranging Placebo 20 mg/Part 2: Bardoxolone methyl 20 mg; Part 1: Dose-Ranging Placebo 5 mg/Part 2: Bardoxolone methyl 5 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult male and female patients ≥ 18 to ≤ 75 years of age upon study consent;
• BMI \> 18.5 kg/m²
• Symptomatic pulmonary hypertension WHO class II and III;
• WHO Group I, III, or V PH according to the following criteria:
• If diagnosed with WHO Group I PAH, then on of the following subtypes:
• Idiopathic or heritable PAH;
• PAH associated with connective tissue disease;
• PAH associated with simple, congenital systemic-to-pulmonary shunts at least 1 year following shunt repair;
• PAH associated with anorexigen or drug-induced toxicity;
• PAH associated with human immunodeficiency virus (HIV); or
• If WHO Group III PH then primary diagnosis must be one of the following subtypes:
• Connective tissue disease associated ILD (CTD-ILD);
• Idiopathic pulmonary fibrosis (IPF);
• Nonspecific interstitial pneumonia (NSIP); or
• If WHO Group V PH then patient must be diagnosed with sarcoidosis;

You may not qualify if:

• Participation in other interventional clinical studies involving pharmaceutical products being tested or used in a way different from the approved form or when used for an unapproved indication within 30 days prior to Day 1;
• Initiation of an exercise program for cardio-pulmonary rehabilitation within 3 months (90 days) prior to Day 1 or planned initiation during Part 1 of the study;
• Stopped receiving any PH chronic therapy within 60 days prior to Day 1;
• Requirement for receipt of intravenous inotropes within 30 days prior to Day 1;
• Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) \> 160 mm Hg or sitting diastolic blood pressure \> 100 mm Hg during Screening after a period of rest;
• Has systolic BP \< 90 mm Hg during Screening after a period of rest;
• WHO Group III or V patients who at rest require supplemental oxygen at a rate of \>4 L/min and have peripheral capillary oxygen saturation levels \<92%;
• Has a history of clinically significant left-sided heart disease and/or clinically significant cardiac disease,including but not limited to any of the following:
• Congenital or acquired valvular disease if clinically significant apart from tricuspid valvular insufficiency due to pulmonary hypertension;
• Pericardial constriction;
• Restrictive or congestive cardiomyopathy;
• Left ventricular ejection fraction \< 40% per echocardiogram (ECHO) within 60 days of Day 1;
• Any current or prior history of symptomatic coronary disease (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or anginal chest pain);
• Acutely decompensated heart failure within 30 days prior to Day 1, as per Investigator assessment;
• History of atrial septostomy within 180 days prior to Day 1;

Sponsors & Collaborators

• Biogen: lead

Study Sites (32)

Banner University Medical Center, Phoenix Advanced Lung Disease Institute

Phoenix, Arizona, 85004, United States

Location

Arizona Pulmonary Specialists

Phoenix, Arizona, 85012, United States

Location

Cedars Sinai Medical Center

Beverly Hills, California, 90211, United States

Location

VA Healthcare System of Greater Los Angeles

Los Angeles, California, 90073, United States

Location

University of California Davis Medical Center - Division of Pulmonary and Critical Care

Sacramento, California, 95817, United States

Location

Harbor - UCLA Medical Center

Torrance, California, 90502, United States

Location

University of Colorado Denver - Division of Pulmonary Sciences

Aurora, Colorado, 80045, United States

Location

South Denver Cardiology Associates, P.C

Littleton, Colorado, 80120, United States

Location

Georgetown University Medical Center - Department of Rheumatology

Washington D.C., District of Columbia, 20007, United States

Location

Cleveland Clinic of Florida

Weston, Florida, 33331, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Maine Medical Center - Division of Pulmonary and Critical Care Medicine

Portland, Maine, 04102, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

Mount Sinai, Beth Israel Medical Center

New York, New York, 10003, United States

Location

Weill Cornell Medical Center

New York, New York, 10021, United States

Location

University of Rochester - University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

The Lindner Clinical Trial Center

Cincinnati, Ohio, 45219, United States

Location

University of Cincinnati - Department of Internal Medicine Pulmonary, Critical Care & Sleep Medicine

Cincinnati, Ohio, 45267, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Oklahoma Heart Hospital

Oklahoma City, Oklahoma, 73120, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

BreatheAmerica El Paso, Inc.

El Paso, Texas, 79912, United States

Location

Houston Methodist Research Institute

Houston, Texas, 77030, United States

Location

The University of Texas - Health Science Center & Medical School at Houston

Houston, Texas, 77030, United States

Location

University of Texas Houston - Division of Rheumatology and Clinical Immunogenetics

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

University Clinic Carl Gustav Carus

Dresden, 01304, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Lung Diseases, Interstitial; Idiopathic Interstitial Pneumonias; Idiopathic Pulmonary Fibrosis; Sarcoidosis; Interstitial Pneumonitis, Desquamative, Familial; Cryptogenic Organizing Pneumonia; Hamman-Rich Syndrome

Interventions

bardoxolone methyl; ORF 50 transactivator

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Pulmonary Fibrosis; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Lung Diseases, Obstructive

Results Point of Contact

• Title: US Biogen Clinical Trial Center
• Organization: Biogen

clinicaltrials@biogen.com

866-633-4636

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2014
• First Posted: January 15, 2014
• Study Start: May 31, 2014
• Primary Completion: January 19, 2018
• Study Completion: May 16, 2018
• Last Updated: June 10, 2025
• Results First Posted: July 23, 2021

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (30); DE (2)