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

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ClinicalTrials.gov Identifier: NCT02657356
Recruitment Status : Terminated (Exposure of these high-risk patients to clinic or in-person visits during the pandemic presented an unacceptable risk to their health)
First Posted : January 15, 2016
Last Update Posted : May 3, 2021
Sponsor:
Information provided by (Responsible Party):
Reata Pharmaceuticals, Inc.

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.

Condition or disease Intervention/treatment Phase
Connective Tissue Disease-Associated Pulmonary Arterial Hypertension Drug: Placebo capsules Drug: Bardoxolone methyl capsules Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 202 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Study of the Efficacy and Safety of Bardoxolone Methyl in Patients With Connective Tissue Disease-associated Pulmonary Arterial Hypertension
Actual Study Start Date : October 4, 2016
Actual Primary Completion Date : May 7, 2020
Actual Study Completion Date : May 7, 2020


Arm Intervention/treatment
Placebo Comparator: Placebo capsules
Placebo capsules will be administered orally once a day for 24 weeks.
Drug: Placebo capsules
Experimental: 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.
Drug: Bardoxolone methyl capsules
Other Name: RTA 402 capsules




Primary Outcome Measures :
  1. Change from baseline in six-minute-walk distance (6MWD) [ Time Frame: 24 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02657356


Locations
Hide Hide 106 study locations
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United States, Arizona
Banner University Medical Center, Phoenix Advanced Lung Disease Institute
Phoenix, Arizona, United States, 85004
Arizona Pulmonary Specialists
Phoenix, Arizona, United States, 85012
United States, California
Cedars Sinai Medical Center
Beverly Hills, California, United States, 90211
Regents of The University of California
Fresno, California, United States, 93701
University of California San Diego
La Jolla, California, United States, 92093
David Geffen School of Medicine UCLA
Los Angeles, California, United States, 90095
Pacific Pulmonary Research, Inc.
San Diego, California, United States, 92103
Santa Barbara Pulmonary Associates
Santa Barbara, California, United States, 93105
Harbor - UCLA Medical Center
Torrance, California, United States, 90502
United States, District of Columbia
Georgetown University Medical Center - Department of Rheumatology
Washington, District of Columbia, United States, 20007
United States, Florida
University of Miami Miller School of Medicine
Miami, Florida, United States, 33136
Cleveland Clinic Florida
Weston, Florida, United States, 33331
United States, Georgia
Augusta University
Augusta, Georgia, United States, 30912
Piedmont-Georgia Lung
Austell, Georgia, United States, 30106
United States, Illinois
University of Illinois at Chicago
Chicago, Illinois, United States, 60612
United States, Kentucky
Kentuckiana Pulmonary Associates
Louisville, Kentucky, United States, 40202
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Boston University School of Medicine
Boston, Massachusetts, United States, 02118
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68131
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87131
United States, New York
NYU Langone Health
New York, New York, United States, 10003
University of Rochester - University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45219
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Wexner Medical Center at The Ohio State University
Columbus, Ohio, United States, 43210
United States, Oklahoma
Integris Nazih Zuhdi Transplant Institute
Oklahoma City, Oklahoma, United States, 73120
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
The Methodist Hospital Research Institute
Houston, Texas, United States, 77030
University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Argentina
Fundación Favaloro
Buenos Aires, Ciudad Autónoma De BuenosAires, Argentina, C1093AAS
Hospital Británico de Buenos Aires
Buenos Aires, Ciudad Autónoma De BuenosAires, Argentina, C1280AEB
Centro Médico Dra de Salvo
Buenos Aires, Ciudad Autónoma De BuenosAires, Argentina, C1426ABP
Instituto de Investigaciones Clínicas Mar Del Plata
Buenos Aires, Mar Del Plata, Argentina, B7600FZN
Instituto De Enfermedades Respiratorias E Investigacion Medica
Buenos Aires, Villa Vatteone, Argentina, B1853AIK
Hospital Cordoba
Cordoba, Argentina, X5004CDP
Hospital Privado Centro Médico de Córdoba
Cordoba, Argentina, X5016KEH
Instituto de Cardiologia de Corrientes Juana Francisca Cabral
Corrientes, Argentina, W3400AMZ
Hospital de Alta Complejidad "Pte. J. D. Perón"
Formosa, Argentina, 3600
Australia, New South Wales
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia, 2050
St Vincent's Hospital Sydney
Darlinghurst, New South Wales, Australia, 2010
John Hunter Hospital
New Lambton, New South Wales, Australia, 2305
Australia, Queensland
Princess Alexandra Hospital
Brisbane, Queensland, Australia, 4102
Australia, Tasmania
Royal Hobart Hospital
Hobart, Tasmania, Australia, 7000
Belgium
UZ Leuven
Leuven, Vlaams Brabant, Belgium, 3000
Hôpital Erasme
Brussels, Belgium, 1070
Brazil
Hospital de Messejana
Fortaleza, Ceara, Brazil, 60864-190
Irmandade Da Santa Casa de Misericordia de Porto Alegre
Porto Alegre, Rio Grande Do Sul, Brazil, 90035-074
Hospital Dia do Pulmão
Blumenau, Santa Catarina, Brazil, 89010-000
Hospital São Paulo
Sao Paulo, Brazil, 04023-900
Instituto do Coração - HCFMUSP
São Paulo, Brazil, 05403-900
Canada, Alberta
Peter Lougheed Centre
Calgary, Alberta, Canada, T1Y 6J4
University of Alberta
Edmonton, Alberta, Canada, T6G 2B7
Canada, British Columbia
Vancouver General Hospital
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Ontario
London Health Sciences Centre
London, Ontario, Canada, N6A 5W9
Canada, Quebec
Centre Hospitalier de l'Université Laval
Sainte Foy, Quebec, Canada, G1V 4G5
Czechia
Vseobecna fakultni nemocnice v Praze
Prague, Czechia, 128 00
Institut klinicke a experimentalni mediciny
Prague, Czechia, 140 00
Germany
Universitätsklinikum Freiburg
Freiburg im Breisgau, Baden-Württemberg, Germany, 79106
Universitatsklinkum Erlangen
Erlangen, Bayern, Germany, 91054
Universität Greifswald
Greifswald, Mecklenburg-Vorpommern, Germany, 17475
DRK Kliniken Berlin Westend
Berlin, Germany, 14050
Universitätsklinikum Carl Gustav Carus an der TU Dresden
Dresden, Germany, 01307
Universitätsklinikum Hamburg Eppendorf
Hamburg, Germany, 20246
Thorax Klinik
Heidelberg, Germany, 69126
Universitätsklinikum Köln
Köln, Germany, 50937
Israel
Hadassah University Hospital Ein Kerem
Jerusalem, Israel, 91120
Rabin Medical Center
Petah Tikva, Israel, 49100
Japan
Nippon Medical School Hospital
Tokyo, Bunkyo-ku, Japan, 113-8603
Kitasato University Hospital
Sagamihara, Kanagawa, Japan, 252-0375
Tohoku University Hospital
Sendai, Miyagi, Japan, 980-8574
National Hospital Organization Okayama Medical Center
Okayama-shi, Okayama, Japan, 701-1192
Chiba University Hospital
Chiba, Japan, 260-8677
Gunma University School of Medicine
Gunma, Japan, 371-8510
Kobe University Hospital
Kobe, Japan, 6500017
Nagoya Medical Center
Nagoya, Japan, 460-0001
Hokkaido University Hospital
Sapporo, Japan, 0608648
Kurume University Medical Center
Sendai-shi, Japan, 980-8574
National Cerebral and Cardiovascular Center
Suita, Japan, 5658565
Fujita Health University Hospital
Toyoake, Japan, 470-1192
Mexico
Instituto Nacional de Cardiologia Dr. Ignacio Chavez
Ciudad de Mexico, Distrito Federal, Mexico, 14080
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Mexico City, Distrito Federal, Mexico, 14000
Hospital Civil Fray Antonio Alcalde
Guadalajara, Jalisco, Mexico, 44280
Hospital Universitario Dr. Jose Eleuterio González
Monterrey, Nuevo Leon, Mexico, 64460
Unidad de Investigación Clínica En Medicina SC
Monterrey, Nuevo Leon, Mexico, 64718
Netherlands
Vrije Universiteit Amsterdam
Amsterdam, Noord-Holland, Netherlands, 1007 MB
Philippines
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, 1100
Spain
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, Spain
Hospital Universitario Vall d'Hebron
Barcelona, Spain, 08035
Hospital de Gran Canaria Doctor Negrin
Las Palmas de Gran Canaria, Spain, 35010
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Hospital Universitario Puerta de Hierro
Majadahonda, Spain
Hospital Virgen de La Salud
Toledo, Spain, 45004
United Kingdom
Golden Jubilee National Hospital
Glasgow, United Kingdom, G81 4HX
Royal Free Hospital
London, United Kingdom, NW3 2QG
Sponsors and Collaborators
Reata Pharmaceuticals, Inc.
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Responsible Party: Reata Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02657356    
Other Study ID Numbers: RTA 402-C-1504
First Posted: January 15, 2016    Key Record Dates
Last Update Posted: May 3, 2021
Last Verified: April 2021
Keywords provided by Reata Pharmaceuticals, Inc.:
Pulmonary Hypertension
Pulmonary Arterial Hypertension
Connective Tissue Disease-Associated Pulmonary Arterial Hypertension
Bardoxolone methyl
PAH
RTA 402
6-minute walk distance
Additional relevant MeSH terms:
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Familial Primary Pulmonary Hypertension
Hypertension
Connective Tissue Diseases
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases