Bardoxolone Methyl in Patients With Connective Tissue Disease-associated Pulmonary Arterial Hypertension - CATALYST

NCT02657356 | Terminated Phase 3 Results DMC

• 1 other identifier: RTA 402-C-1504
• Study Type: interventional
• Target: 202
• Locations: 15 countries
• Sites: 106

Brief Summary

This study assesses the safety and efficacy of bardoxolone methyl relative to placebo in patients with connective tissue disease-associated pulmonary arterial hypertension to determine the recommended dose range and evaluate the change from baseline in 6-minute walk distance (6MWD) following 24 weeks of study participation.

Conditions

Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Keywords

Pulmonary Hypertension; Pulmonary Arterial Hypertension; Connective Tissue Disease-Associated Pulmonary Arterial Hypertension; Bardoxolone methyl; PAH; RTA 402; 6-minute walk distance

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Six-minute-walk Distance (6MWD) Relative to Placebo at Week 24

  Baseline through 24 weeks after participant receives the first dose

Secondary Outcomes (1)

• Time to First Persistent Clinical Improvement Event

  Baseline through the end of the study

Study Arms (2)

Placebo capsules

PLACEBO COMPARATOR

Placebo capsules will be administered orally once a day for 24 weeks.

Drug: Placebo capsules

Bardoxolone methyl capsules

EXPERIMENTAL

Each patient will receive bardoxolone methyl capsules administered orally once a day for 24 weeks. Starting dosage for each patient is 5 mg and will dose-escalate to 10 mg at Week 4, unless contraindicated clinically.

Drug: Bardoxolone methyl capsules

Interventions

Placebo capsules DRUG

Placebo capsules

Bardoxolone methyl capsules DRUG

Also known as: RTA 402 capsules

Bardoxolone methyl capsules

Eligibility Criteria

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

You may qualify if:

• BMI \> 18.5 kg/m2;
• Symptomatic pulmonary hypertension WHO/NYHA FC class II and III;
• WHO Group I PAH associated with connective tissue disease;
• Had a diagnostic right heart catheterization performed and documented within 36 months prior to Day 1 that confirmed a diagnosis of PAH according to all the following criteria:
• Mean pulmonary artery pressure ≥ 25 mm Hg (at rest);
• Pulmonary capillary wedge pressure (PCWP) ≤ 15 mm Hg;
• Pulmonary vascular resistance \> 240 dyn.sec/cm5 or \> 3 mm Hg/liter (L)/minute;
• Has BNP level ≤ 400 pg/mL;
• Had an average 6MWD ≥ 150 meters on two consecutive tests performed on different days prior to randomization, with both tests measuring within 15% of one another;
• Has been receiving no more than two (2) approved disease-specific PAH therapies. PAH therapy must have been at a stable dose for at least 90 days prior to Day 1. No additions or changes should be made to PAH therapies and doses should remain stable for the duration of the study;
• Has maintained a stable dose for 30 days prior to Day 1 if receiving any of the following therapies that may affect PAH: vasodilators (including calcium channel blockers), digoxin, L-arginine supplementation, or oxygen supplementation. No additions or changes should be made to therapies and doses should remain stable for the duration of the study;
• If receiving treatment for CTD with prednisone or any other drugs, doses must remain stable for at least 30 days prior to Day 1 and for the duration of the study Had pulmonary function tests (PFTs) within 90 days prior to Day 1 with total lung capacity ≥ 65% (predicted);
• Had a ventilation-perfusion (V/Q) lung scan, spiral/helical/electron beam computed tomography (CT), or pulmonary angiogram prior to Day 1 that shows no evidence of thromboembolic disease (i.e., should note normal or low probability for pulmonary embolism). If V/Q scan was abnormal (i.e., results other than normal or low probability), then a confirmatory CT or selective pulmonary angiography must exclude chronic thromboembolic pulmonary hypertension;
• Has adequate kidney function defined as an estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2 as measured by the central lab;
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;

You may not qualify if:

• Participation in other investigational clinical studies involving interventional 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 90 days prior to Day 1 or planned initiation during the study;
• Stopped receiving any PAH chronic therapy within 60 days prior to Day 1;
• Received a dose of prednisone \> 20 mg/day (or equivalent dose if other corticosteroid) within 30 days prior to Day 1;
• Received intravenous (iv) or subcutaneous (sc) prostacyclin/prostacyclin analogues within 90 days prior to Day 1;
• Received 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 BP \> 100 mm Hg during Screening after a period of rest;
• Has systolic BP \< 90 mm Hg during Screening after a period of rest;
• 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 90 days of Day 1;
• Symptomatic coronary artery disease within the last 3 years;
• Acutely decompensated heart failure within 30 days prior to Day 1, per investigator assessment;

Sponsors & Collaborators

• Biogen: lead

Study Sites (106)

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

Regents of The University of California

Fresno, California, 93701, United States

Location

University of California San Diego

La Jolla, California, 92093, United States

Location

David Geffen School of Medicine UCLA

Los Angeles, California, 90095, United States

Location

Pacific Pulmonary Research, Inc.

San Diego, California, 92103, United States

Location

Santa Barbara Pulmonary Associates

Santa Barbara, California, 93105, United States

Location

Harbor - UCLA Medical Center

Torrance, California, 90502, United States

Location

Georgetown University Medical Center - Department of Rheumatology

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

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Piedmont-Georgia Lung

Austell, Georgia, 30106, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Kentuckiana Pulmonary Associates

Louisville, Kentucky, 40202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68131, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

NYU Langone Health

New York, New York, 10003, United States

Location

University of Rochester - University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Wexner Medical Center at The Ohio State University

Columbus, Ohio, 43210, United States

Location

Integris Nazih Zuhdi Transplant Institute

Oklahoma City, Oklahoma, 73120, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

The Methodist Hospital Research Institute

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Fundación Favaloro

Buenos Aires, Ciudad Autónoma de BuenosAires, C1093AAS, Argentina

Location

Hospital Británico de Buenos Aires

Buenos Aires, Ciudad Autónoma de BuenosAires, C1280AEB, Argentina

Location

Centro Médico Dra de Salvo

Buenos Aires, Ciudad Autónoma de BuenosAires, C1426ABP, Argentina

Location

Instituto de Investigaciones Clínicas Mar Del Plata

Buenos Aires, Mar Del Plata, B7600FZN, Argentina

Location

Instituto De Enfermedades Respiratorias E Investigacion Medica

Buenos Aires, Villa Vatteone, B1853AIK, Argentina

Location

Instituto de Cardiologia de Corrientes Juana Francisca Cabral

Corrientes, W3400AMZ, Argentina

Location

Hospital Cordoba

Córdoba, X5004CDP, Argentina

Location

Hospital Privado Centro Médico de Córdoba

Córdoba, X5016KEH, Argentina

Location

Hospital de Alta Complejidad "Pte. J. D. Perón"

Formosa, 3600, Argentina

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

John Hunter Hospital

New Lambton, New South Wales, 2305, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

UZ Leuven

Leuven, Vlaams Brabant, 3000, Belgium

Location

Hôpital Erasme

Brussels, 1070, Belgium

Location

Hospital de Messejana

Fortaleza, Ceará, 60864-190, Brazil

Location

Irmandade Da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-074, Brazil

Location

Hospital Dia do Pulmão

Blumenau, Santa Catarina, 89010-000, Brazil

Location

Hospital São Paulo

São Paulo, 04023-900, Brazil

Location

Instituto do Coração - HCFMUSP

São Paulo, 05403-900, Brazil

Location

Peter Lougheed Centre

Calgary, Alberta, T1Y 6J4, Canada

Location

University of Alberta

Edmonton, Alberta, T6G 2B7, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Centre Hospitalier de l'Université Laval

Sainte-Foy, Quebec, G1V 4G5, Canada

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 00, Czechia

Location

Institut klinicke a experimentalni mediciny

Prague, 140 00, Czechia

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Universitatsklinkum Erlangen

Erlangen, Bavaria, 91054, Germany

Location

Universität Greifswald

Greifswald, Mecklenburg-Vorpommern, 17475, Germany

Location

DRK Kliniken Berlin Westend

Berlin, 14050, Germany

Location

Universitätsklinikum Köln

Cologne, 50937, Germany

Location

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Thorax Klinik

Heidelberg, 69126, Germany

Location

Hadassah University Hospital Ein Kerem

Jerusalem, 91120, Israel

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Nippon Medical School Hospital

Tokyo, Bunkyo-ku, 113-8603, Japan

Location

Kitasato University Hospital

Sagamihara, Kanagawa, 252-0375, Japan

Location

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

Location

National Hospital Organization Okayama Medical Center

Okayama, Okayama-ken, 701-1192, Japan

Location

Chiba University Hospital

Chiba, 260-8677, Japan

Location

Gunma University School of Medicine

Gunma, 371-8510, Japan

Location

Kobe University Hospital

Kobe, 6500017, Japan

Location

Nagoya Medical Center

Nagoya, 460-0001, Japan

Location

Hokkaido University Hospital

Sapporo, 0608648, Japan

Location

Kurume University Medical Center

Sendai, 980-8574, Japan

Location

National Cerebral and Cardiovascular Center

Suita, 5658565, Japan

Location

Fujita Health University Hospital

Toyoake, 470-1192, Japan

Location

Hospital Civil Fray Antonio Alcalde

Guadalajara, Jalisco, 44280, Mexico

Location

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, Mexico City, 14000, Mexico

Location

Instituto Nacional de Cardiologia Dr. Ignacio Chavez

Mexico City, Mexico City, 14080, Mexico

Location

Hospital Universitario Dr. Jose Eleuterio González

Monterrey, Nuevo León, 64460, Mexico

Location

Unidad de Investigación Clínica En Medicina SC

Monterrey, Nuevo León, 64718, Mexico

Location

Vrije Universiteit Amsterdam

Amsterdam, North Holland, 1007 MB, Netherlands

Location

Angeles University Foundation Medical Center (AUFMC)

Angeles City, Philippines

Location

Mary Mediatrix Medical Center (MMMC)

Lipa, Philippines

Location

Makati Medical Center (MMC)

Makati, Philippines

Location

Philippine General Hospital (PGH)

Manila, Philippines

Location

Philippine Heart Center (PHC)

Quezon City, 1100, Philippines

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital de Gran Canaria Doctor Negrin

Las Palmas de Gran Canaria, 35010, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Spain

Location

Hospital Virgen de La Salud

Toledo, 45004, Spain

Location

Golden Jubilee National Hospital

Glasgow, G81 4HX, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; Pulmonary Arterial Hypertension

Interventions

bardoxolone methyl; ORF 50 transactivator

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2016
• First Posted: January 15, 2016
• Study Start: October 4, 2016
• Primary Completion: May 7, 2020
• Study Completion: May 7, 2020
• Last Updated: June 4, 2025
• Results First Posted: May 19, 2023

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

BE (2); JP (12); CZ (2); ME (5); GB (2); BR (5); IL (2); ES (6); US (37); AR (9); CA (5); NL (1); PH (5); DE (8); AU (5)