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Connective Tissue Disease-Associated Pulmonary Arterial HypertensionPhase 3NCT02657356

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

A Phase 3 study testing Bardoxolone methyl capsules in people with Connective Tissue Disease-Associated Pulmonary Arterial Hypertension, run by Biogen at 106 sites in 15 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Bardoxolone methyl capsules
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
202 participants
Where
106 sitesin 15 countries
Study dates
4 Oct 2016to 7 May 2020
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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

Who cannot join

  • 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;
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  • 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.

Trial locations and contacts

106 sites in 15 countries.

106 sites in 15 countries

United States37 sites

  • University of New Mexico

    Albuquerque, New Mexico, 87131

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Augusta University

    Augusta, Georgia, 30912

  • Piedmont-Georgia Lung

    Austell, Georgia, 30106

  • Cedars Sinai Medical Center

    Beverly Hills, California, 90211

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Boston University School of Medicine

    Boston, Massachusetts, 02118

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Illinois at Chicago

    Chicago, Illinois, 60612

  • University of Cincinnati

    Cincinnati, Ohio, 45219

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Wexner Medical Center at The Ohio State University

    Columbus, Ohio, 43210

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Regents of The University of California

    Fresno, California, 93701

  • The Methodist Hospital Research Institute

    Houston, Texas, 77030

  • University of Texas Health Science Center at Houston

    Houston, Texas, 77030

  • University of California San Diego

    La Jolla, California, 92093

  • David Geffen School of Medicine UCLA

    Los Angeles, California, 90095

  • Kentuckiana Pulmonary Associates

    Louisville, Kentucky, 40202

  • University of Miami Miller School of Medicine

    Miami, Florida, 33136

  • NYU Langone Health

    New York, New York, 10003

  • Integris Nazih Zuhdi Transplant Institute

    Oklahoma City, Oklahoma, 73120

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68131

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Banner University Medical Center, Phoenix Advanced Lung Disease Institute

    Phoenix, Arizona, 85004

  • Arizona Pulmonary Specialists

    Phoenix, Arizona, 85012

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • University of Rochester - University of Rochester Medical Center

    Rochester, New York, 14642

  • University of Utah

    Salt Lake City, Utah, 84132

  • Pacific Pulmonary Research, Inc.

    San Diego, California, 92103

  • Santa Barbara Pulmonary Associates

    Santa Barbara, California, 93105

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Harbor - UCLA Medical Center

    Torrance, California, 90502

  • Georgetown University Medical Center - Department of Rheumatology

    Washington D.C., District of Columbia, 20007

  • Cleveland Clinic Florida

    Weston, Florida, 33331

Other trials in United States

Japan12 sites

  • Chiba University Hospital

    Chiba, 260-8677

  • Gunma University School of Medicine

    Gunma, 371-8510

  • Kobe University Hospital

    Kobe, 6500017

  • Nagoya Medical Center

    Nagoya, 460-0001

  • National Hospital Organization Okayama Medical Center

    Okayama, Okayama-ken, 701-1192

  • Kitasato University Hospital

    Sagamihara, Kanagawa, 252-0375

  • Hokkaido University Hospital

    Sapporo, 0608648

  • Tohoku University Hospital

    Sendai, Miyagi, 980-8574

  • Kurume University Medical Center

    Sendai, 980-8574

  • National Cerebral and Cardiovascular Center

    Suita, 5658565

  • Nippon Medical School Hospital

    Tokyo, Bunkyo-ku, 113-8603

  • Fujita Health University Hospital

    Toyoake, 470-1192

Other trials in Japan

Argentina9 sites

  • Fundación Favaloro

    Buenos Aires, Ciudad Autónoma de BuenosAires, C1093AAS

  • Hospital Británico de Buenos Aires

    Buenos Aires, Ciudad Autónoma de BuenosAires, C1280AEB

  • Centro Médico Dra de Salvo

    Buenos Aires, Ciudad Autónoma de BuenosAires, C1426ABP

  • Instituto de Investigaciones Clínicas Mar Del Plata

    Buenos Aires, Mar Del Plata, B7600FZN

  • Instituto De Enfermedades Respiratorias E Investigacion Medica

    Buenos Aires, Villa Vatteone, B1853AIK

  • Hospital Cordoba

    Córdoba, X5004CDP

  • Hospital Privado Centro Médico de Córdoba

    Córdoba, X5016KEH

  • Instituto de Cardiologia de Corrientes Juana Francisca Cabral

    Corrientes, W3400AMZ

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

    Formosa, 3600

Other trials in Argentina

Germany8 sites

  • DRK Kliniken Berlin Westend

    Berlin, 14050

  • Universitätsklinikum Köln

    Cologne, 50937

  • Universitätsklinikum Carl Gustav Carus an der TU Dresden

    Dresden, 01307

  • Universitatsklinkum Erlangen

    Erlangen, Bavaria, 91054

  • Universitätsklinikum Freiburg

    Freiburg im Breisgau, Baden-Wurttemberg, 79106

  • Universität Greifswald

    Greifswald, Mecklenburg-Vorpommern, 17475

  • Universitätsklinikum Hamburg Eppendorf

    Hamburg, 20246

  • Thorax Klinik

    Heidelberg, 69126

Other trials in Germany

Spain6 sites

  • Hospital Universitario Vall d'Hebron

    Barcelona, 08035

  • Hospital de Gran Canaria Doctor Negrin

    Las Palmas de Gran Canaria, 35010

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario Puerta de Hierro

    Majadahonda

  • Hospital Universitario Marques de Valdecilla

    Santander, Cantabria

  • Hospital Virgen de La Salud

    Toledo, 45004

Other trials in Spain

Australia5 sites

  • Princess Alexandra Hospital

    Brisbane, Queensland, 4102

  • Royal Prince Alfred Hospital

    Camperdown, New South Wales, 2050

  • St Vincent's Hospital Sydney

    Darlinghurst, New South Wales, 2010

  • Royal Hobart Hospital

    Hobart, Tasmania, 7000

  • John Hunter Hospital

    New Lambton, New South Wales, 2305

Other trials in Australia

Brazil5 sites

  • Hospital Dia do Pulmão

    Blumenau, Santa Catarina, 89010-000

  • Hospital de Messejana

    Fortaleza, Ceará, 60864-190

  • Irmandade Da Santa Casa de Misericordia de Porto Alegre

    Porto Alegre, Rio Grande do Sul, 90035-074

  • Hospital São Paulo

    São Paulo, 04023-900

  • Instituto do Coração - HCFMUSP

    São Paulo, 05403-900

Other trials in Brazil

Canada5 sites

  • Peter Lougheed Centre

    Calgary, Alberta, T1Y 6J4

  • University of Alberta

    Edmonton, Alberta, T6G 2B7

  • London Health Sciences Centre

    London, Ontario, N6A 5W9

  • Centre Hospitalier de l'Université Laval

    Sainte-Foy, Quebec, G1V 4G5

  • Vancouver General Hospital

    Vancouver, British Columbia, V5Z 1M9

Other trials in Canada

Mexico5 sites

  • Hospital Civil Fray Antonio Alcalde

    Guadalajara, Jalisco, 44280

  • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

    Mexico City, Mexico City, 14000

  • Instituto Nacional de Cardiologia Dr. Ignacio Chavez

    Mexico City, Mexico City, 14080

  • Hospital Universitario Dr. Jose Eleuterio González

    Monterrey, Nuevo León, 64460

  • Unidad de Investigación Clínica En Medicina SC

    Monterrey, Nuevo León, 64718

Other trials in Mexico

Philippines5 sites

  • Angeles University Foundation Medical Center (AUFMC)

    Angeles City

  • Mary Mediatrix Medical Center (MMMC)

    Lipa

  • Makati Medical Center (MMC)

    Makati

  • Philippine General Hospital (PGH)

    Manila

  • Philippine Heart Center (PHC)

    Quezon City, 1100

Other trials in Philippines

Belgium2 sites

  • Hôpital Erasme

    Brussels, 1070

  • UZ Leuven

    Leuven, Vlaams Brabant, 3000

Other trials in Belgium

Czechia2 sites

  • Vseobecna fakultni nemocnice v Praze

    Prague, 128 00

  • Institut klinicke a experimentalni mediciny

    Prague, 140 00

Other trials in Czechia

Israel2 sites

  • Hadassah University Hospital Ein Kerem

    Jerusalem, 91120

  • Rabin Medical Center

    Petah Tikva, 49100

Other trials in Israel

United Kingdom2 sites

  • Golden Jubilee National Hospital

    Glasgow, G81 4HX

  • Royal Free Hospital

    London, NW3 2QG

Other trials in United Kingdom

Netherlands1 site

  • Vrije Universiteit Amsterdam

    Amsterdam, North Holland, 1007 MB

Other trials in Netherlands

About this study

Official title: A Study of the Efficacy and Safety of Bardoxolone Methyl in Patients With Connective Tissue Disease-associated Pulmonary Arterial Hypertension

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.

Read the 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.

Being tested
Placebo capsules, Bardoxolone methyl capsules
Keywords
Pulmonary Hypertension, Pulmonary Arterial Hypertension, Connective Tissue Disease-Associated Pulmonary Arterial Hypertension, Bardoxolone methyl, PAH, RTA 402, 6-minute walk distance
Medical subject headings
Hypertension, Pulmonary, Pulmonary Arterial Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Placebo capsulesDrug

  • Bardoxolone methyl capsulesDrug

    Also called RTA 402 capsules

Study groups in NCT02657356
Study groupRoleWhat they receive
Placebo capsulesPlacebo comparatorPlacebo capsules will be administered orally once a day for 24 weeks.
Receives: Drug: Placebo capsules
Bardoxolone methyl capsulesExperimentalEach 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.
Receives: Drug: Bardoxolone methyl capsules

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Baseline through 24 weeks after participant receives the first dose

Secondary outcomes (1)

  1. Time to First Persistent Clinical Improvement Event

    At least one of the following four criteria must have been met:

    1. Improvement by at least one WHO functional class coupled with no more than a 15% decrease from baseline in 6MWT
    2. Increase from baseline in 6MWT by at least 10% and stability or improvement in the WHO functional class
    3. Decrease from baseline in creatine kinase (a surrogate biomarker for muscle injury and inflammation) by at least 10% and no worsening in WHO functional class and no more than a 15% decrease from baseline in 6MWT
    4. Improvement in estimated glomerular filtration rate eGFR ≥10% of baseline The persistence of the change in WHO functional class, 6MWT, eGFR, or creatine kinase must be confirmed by a subsequent assessment at least 14 days after the initial assessment, or at the next scheduled assessment. If persistent improvement is confirmed, the date of the event was considered the initial assessment of improved WHO functional class, 6MWT, eGFR, or creatine kinase.

    Measured: Baseline through the end of the study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jan 2016 (estimated)
  2. Study start4 Oct 2016
  3. Primary completion7 May 2020
  4. Study completion7 May 2020

Why it stopped: Exposure of these high-risk patients to clinic or in-person visits during the pandemic presented an unacceptable risk to their health

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
202 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02657356
Sponsor's protocol ID
RTA 402-C-1504
Status last verified
May 2025
First submitted
13 Jan 2016
Last updated
4 Jun 2025
Data monitoring committee
Yes
Individual data sharing
Yes: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bardoxolone methyl capsules in people with Connective Tissue Disease-Associated Pulmonary Arterial Hypertension, run by Biogen at 106 sites in 15 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 106 sites in United States, Japan, Argentina, Germany, Spain and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Six-minute-walk Distance (6MWD) Relative to Placebo at Week 24 (time frame: Baseline through 24 weeks after participant receives the first dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02657356.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2025.

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