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

NCT ID: NCT02657356

Last Updated: 2025-06-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 202 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-04
• Study Completion Date: 2020-05-07

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.

Detailed Description

This double-blind, randomized, placebo-controlled trial will study the safety, tolerability, and efficacy of bardoxolone methyl in qualified patients with World Health Organization Group I Connective Tissue Disease Pulmonary Arterial Hypertension (WHO Group I CTD-PAH).

Qualified patients will be randomized 1:1 to either bardoxolone methyl or placebo to be administered once daily for 24 weeks. Patients randomized to placebo will remain on placebo throughout the study. Patients randomized to bardoxolone methyl will start at 5 mg and will dose-escalate to 10 mg at Week 4 unless contraindicated clinically. Dose de-escalation is permitted during the study if indicated clinically.

All patients in the study will follow the same visit and assessment schedule. Following randomization, patients will be scheduled to be assessed in person during treatment at Weeks 1, 2, 4, 6, 8, 16, and 24 and by telephone contact on Days 3, 10, 21, 31, 38, 84, and 140. Patients will also be scheduled to be assessed at an in person follow up visit at Week 28, four weeks after the end of treatment.

Conditions

Connective Tissue Disease-Associated Pulmonary Arterial Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo capsules

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

Group Type: PLACEBO_COMPARATOR

Placebo capsules

Intervention Type: DRUG

Bardoxolone methyl capsules

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.

Group Type: EXPERIMENTAL

Bardoxolone methyl capsules

Intervention Type: DRUG

Interventions

Placebo capsules

Intervention Type: DRUG

Bardoxolone methyl capsules

Intervention Type: DRUG

Other Intervention Names

RTA 402 capsules

Eligibility Criteria

Inclusion Criteria

• 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;
• Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study prior to initiation of any patient-mandated procedures

Exclusion Criteria

• 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;
• Has more than two of the following clinical risk factors for left ventricular diastolic dysfunction:

• Age > 65 years;
• BMI ≥ 30 kg/m2;
• History of systemic hypertension;
• History of type 2 diabetes;
• History of atrial fibrillation;
• History of atrial septostomy within 180 days prior to Day 1;
• History of uncontrolled obstructive sleep apnea;
• Has a history of portal hypertension or chronic liver disease, including hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication) defined as mild to severe hepatic impairment (Child-Pugh Class A-C);
• Serum aminotransferase (ALT or AST) levels > 1.5X the upper limit of normal (ULN) at Screening;
• Hemoglobin (Hgb) concentration < 8.5 g/dL at Screening;
• Diagnosis of Down syndrome;
• History of malignancy within 5 years prior to screening, with the exception of localized skin or cervical carcinomas;
• Untreated or uncontrolled active bacterial, fungal, or viral infection;
• Known or suspected active drug or alcohol abuse, per investigator judgment;
• Use of Herbalife supplements within 14 days prior to Day 1;
• Major surgery within 30 days prior to Day 1 or planned to occur during the course of the study;
• Unwilling to practice acceptable methods of birth control (both males who have partners of childbearing potential and females of childbearing potential) during screening, while taking study drug, and for at least 30 days after the last dose of study drug is ingested;
• Use of inhaled nitric oxide within 7 days prior to Screening and Day 1 visits, excluding acute vasodilator testing during diagnostic cardiac catheterization;
• Women who are pregnant or breastfeeding;
• Any disability or impairment that would prohibit performance of the 6MWT;
• Any abnormal laboratory level that, in the opinion of the investigator, would put the patient at risk by trial enrollment;
• Patient is, in the opinion of the investigator, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason;
• Known hypersensitivity to any component of the study drug;
• Unable to communicate or cooperate with the investigator because of language problems, poor mental development, or impaired cerebral function.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biogen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Banner University Medical Center, Phoenix Advanced Lung Disease Institute

Phoenix, Arizona, United States

Arizona Pulmonary Specialists

Phoenix, Arizona, United States

Cedars Sinai Medical Center

Beverly Hills, California, United States

Regents of The University of California

Fresno, California, United States

University of California San Diego

La Jolla, California, United States

David Geffen School of Medicine UCLA

Los Angeles, California, United States

Pacific Pulmonary Research, Inc.

San Diego, California, United States

Santa Barbara Pulmonary Associates

Santa Barbara, California, United States

Harbor - UCLA Medical Center

Torrance, California, United States

Georgetown University Medical Center - Department of Rheumatology

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

University of Miami Miller School of Medicine

Miami, Florida, United States

Cleveland Clinic Florida

Weston, Florida, United States

Augusta University

Augusta, Georgia, United States

Piedmont-Georgia Lung

Austell, Georgia, United States

University of Illinois at Chicago

Chicago, Illinois, United States

Kentuckiana Pulmonary Associates

Louisville, Kentucky, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Boston University School of Medicine

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

University of New Mexico

Albuquerque, New Mexico, United States

NYU Langone Health

New York, New York, United States

University of Rochester - University of Rochester Medical Center

Rochester, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

University of Cincinnati

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Wexner Medical Center at The Ohio State University

Columbus, Ohio, United States

Integris Nazih Zuhdi Transplant Institute

Oklahoma City, Oklahoma, United States

Oregon Health & Science University

Portland, Oregon, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

The Methodist Hospital Research Institute

Houston, Texas, United States

University of Texas Health Science Center at Houston

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Fundación Favaloro

Buenos Aires, Ciudad Autónoma de BuenosAires, Argentina

Hospital Británico de Buenos Aires

Buenos Aires, Ciudad Autónoma de BuenosAires, Argentina

Centro Médico Dra de Salvo

Buenos Aires, Ciudad Autónoma de BuenosAires, Argentina

Instituto de Investigaciones Clínicas Mar Del Plata

Buenos Aires, Mar Del Plata, Argentina

Instituto De Enfermedades Respiratorias E Investigacion Medica

Buenos Aires, Villa Vatteone, Argentina

Instituto de Cardiologia de Corrientes Juana Francisca Cabral

Corrientes, , Argentina

Hospital Cordoba

Córdoba, , Argentina

Hospital Privado Centro Médico de Córdoba

Córdoba, , Argentina

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

Formosa, , Argentina

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia

John Hunter Hospital

New Lambton, New South Wales, Australia

Princess Alexandra Hospital

Brisbane, Queensland, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

UZ Leuven

Leuven, Vlaams Brabant, Belgium

Hôpital Erasme

Brussels, , Belgium

Hospital de Messejana

Fortaleza, Ceará, Brazil

Irmandade Da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Dia do Pulmão

Blumenau, Santa Catarina, Brazil

Hospital São Paulo

São Paulo, , Brazil

Instituto do Coração - HCFMUSP

São Paulo, , Brazil

Peter Lougheed Centre

Calgary, Alberta, Canada

University of Alberta

Edmonton, Alberta, Canada

Vancouver General Hospital

Vancouver, British Columbia, Canada

London Health Sciences Centre

London, Ontario, Canada

Centre Hospitalier de l'Université Laval

Sainte-Foy, Quebec, Canada

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

Institut klinicke a experimentalni mediciny

Prague, , Czechia

Universitätsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Universitatsklinkum Erlangen

Erlangen, Bavaria, Germany

Universität Greifswald

Greifswald, Mecklenburg-Vorpommern, Germany

DRK Kliniken Berlin Westend

Berlin, , Germany

Universitätsklinikum Köln

Cologne, , Germany

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, , Germany

Universitätsklinikum Hamburg Eppendorf

Hamburg, , Germany

Thorax Klinik

Heidelberg, , Germany

Hadassah University Hospital Ein Kerem

Jerusalem, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Nippon Medical School Hospital

Tokyo, Bunkyo-ku, Japan

Kitasato University Hospital

Sagamihara, Kanagawa, Japan

Tohoku University Hospital

Sendai, Miyagi, Japan

National Hospital Organization Okayama Medical Center

Okayama, Okayama-ken, Japan

Chiba University Hospital

Chiba, , Japan

Gunma University School of Medicine

Gunma, , Japan

Kobe University Hospital

Kobe, , Japan

Nagoya Medical Center

Nagoya, , Japan

Hokkaido University Hospital

Sapporo, , Japan

Kurume University Medical Center

Sendai, , Japan

National Cerebral and Cardiovascular Center

Suita, , Japan

Fujita Health University Hospital

Toyoake, , Japan

Hospital Civil Fray Antonio Alcalde

Guadalajara, Jalisco, Mexico

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Mexico City, Mexico City, Mexico

Instituto Nacional de Cardiologia Dr. Ignacio Chavez

Mexico City, Mexico City, Mexico

Hospital Universitario Dr. Jose Eleuterio González

Monterrey, Nuevo León, Mexico

Unidad de Investigación Clínica En Medicina SC

Monterrey, Nuevo León, Mexico

Vrije Universiteit Amsterdam

Amsterdam, North Holland, Netherlands

Angeles University Foundation Medical Center (AUFMC)

Angeles City, , Philippines

Mary Mediatrix Medical Center (MMMC)

Lipa, , Philippines

Makati Medical Center (MMC)

Makati, , Philippines

Philippine General Hospital (PGH)

Manila, , Philippines

Philippine Heart Center (PHC)

Quezon City, , Philippines

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, Spain

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Hospital de Gran Canaria Doctor Negrin

Las Palmas de Gran Canaria, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario Puerta de Hierro

Majadahonda, , Spain

Hospital Virgen de La Salud

Toledo, , Spain

Golden Jubilee National Hospital

Glasgow, , United Kingdom

Royal Free Hospital

London, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Brazil; Canada; Czechia; Germany; Israel; Japan; Mexico; Netherlands; Philippines; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

RTA 402-C-1504

Identifier Type: -

Identifier Source: org_study_id