Bardoxolone Methyl in Patients With Connective Tissue Disease-associated Pulmonary Arterial Hypertension - CATALYST
Study Purpose
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.
Recruitment Criteria
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
Eligible Ages | 18 Years - 75 Years |
Gender | All |
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.
- - 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.
- - 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.
- - 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).
- - 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.
Trial Details
Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT02657356 |
Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 3 |
Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
Reata Pharmaceuticals, Inc. |
Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
N/A |
Principal Investigator Affiliation | N/A |
Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Industry |
Overall Status | Active, not recruiting |
Countries | Argentina, Australia, Belgium, Brazil, Canada, Czechia, Germany, Israel, Japan, Mexico, Netherlands, Philippines, Spain, United Kingdom, United States |
Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Connective Tissue Disease-Associated Pulmonary Arterial Hypertension |
This double-blind, randomized, placebo-controlled trial will study the safety, tolerability, and efficacy of bardoxolone methyl in qualified patients with 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.
Arms
Placebo Comparator: Placebo capsules
Placebo capsules will be administered orally once a day for 24 weeks.
Experimental: Bardoxolone methyl capsules
Bardoxolone methyl capsules will be administered orally once a day for 24 weeks. Starting dosage is 5 mg and will dose-escalate to 10 mg at Week 4, unless contraindicated clinically.
Interventions
Drug: - Placebo capsules
Drug: - Bardoxolone methyl capsules
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Address
Banner University Medical Center, Phoenix Advanced Lung Disease Institute
Phoenix, Arizona, 85004
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Arizona Pulmonary Specialists
Phoenix, Arizona, 85012
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Cedars Sinai Medical Center
Beverly Hills, California, 90211
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Regents of The University of California
Fresno, California, 93701
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University of California San Diego
La Jolla, California, 92093
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David Geffen School of Medicine UCLA
Los Angeles, California, 90095
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Pacific Pulmonary Research, Inc.
San Diego, California, 92103
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Santa Barbara Pulmonary Associates
Santa Barbara, California, 93105
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Harbor - UCLA Medical Center
Torrance, California, 90502
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Georgetown University Medical Center - Department of Rheumatology
Washington, District of Columbia, 20007
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University of Miami Miller School of Medicine
Miami, Florida, 33136
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Cleveland Clinic Florida
Weston, Florida, 33331
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Augusta University
Augusta, Georgia, 30912
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Piedmont-Georgia Lung
Austell, Georgia, 30106
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University of Illinois at Chicago
Chicago, Illinois, 60612
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Kentuckiana Pulmonary Associates
Louisville, Kentucky, 40202
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Massachusetts General Hospital
Boston, Massachusetts, 02114
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Boston University School of Medicine
Boston, Massachusetts, 02118
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University of Michigan
Ann Arbor, Michigan, 48109
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Washington University School of Medicine
Saint Louis, Missouri, 63110
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University of Nebraska Medical Center
Omaha, Nebraska, 68131
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University of New Mexico
Albuquerque, New Mexico, 87131
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NYU Langone Health
New York, New York, 10003
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University of Rochester - University of Rochester Medical Center
Rochester, New York, 14642
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Duke University Medical Center
Durham, North Carolina, 27710
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University of Cincinnati
Cincinnati, Ohio, 45219
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Cleveland Clinic
Cleveland, Ohio, 44195
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Wexner Medical Center at The Ohio State University
Columbus, Ohio, 43210
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Integris Nazih Zuhdi Transplant Institute
Oklahoma City, Oklahoma, 73120
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Oregon Health & Science University
Portland, Oregon, 97239
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University of Pennsylvania
Philadelphia, Pennsylvania, 19104
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Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
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Medical University of South Carolina
Charleston, South Carolina, 29425
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University of Texas Southwestern Medical Center
Dallas, Texas, 75390
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The Methodist Hospital Research Institute
Houston, Texas, 77030
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University of Texas Health Science Center at Houston
Houston, Texas, 77030
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University of Utah
Salt Lake City, Utah, 84132
International Sites
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Fundación Favaloro
Buenos Aires, Ciudad Autónoma De BuenosAires, C1093AAS
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Hospital Británico de Buenos Aires
Buenos Aires, Ciudad Autónoma De BuenosAires, C1280AEB
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Centro Médico Dra de Salvo
Buenos Aires, Ciudad Autónoma De BuenosAires, C1426ABP
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Instituto de Investigaciones Clínicas Mar Del Plata
Buenos Aires, Mar Del Plata, B7600FZN
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Instituto De Enfermedades Respiratorias E Investigacion Medica
Buenos Aires, Villa Vatteone, B1853AIK
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Hospital Cordoba
Cordoba, , X5004CDP
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Hospital Privado Centro Médico de Córdoba
Cordoba, , X5016KEH
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Instituto de Cardiologia de Corrientes Juana Francisca Cabral
Corrientes, , W3400AMZ
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Hospital de Alta Complejidad "Pte. J. D. Perón"
Formosa, , 3600
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Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
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St Vincent's Hospital Sydney
Darlinghurst, New South Wales, 2010
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John Hunter Hospital
New Lambton, New South Wales, 2305
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Princess Alexandra Hospital
Brisbane, Queensland, 4102
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Royal Hobart Hospital
Hobart, Tasmania, 7000
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UZ Leuven
Leuven, Vlaams Brabant, 3000
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Hôpital Erasme
Brussels, , 1070
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Hospital de Messejana
Fortaleza, Ceara, 60864-190
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Irmandade Da Santa Casa de Misericordia de Porto Alegre
Porto Alegre, Rio Grande Do Sul, 90035-074
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Hospital Dia do Pulmão
Blumenau, Santa Catarina, 89010-000
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Hospital São Paulo
Sao Paulo, , 04023-900
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Instituto do Coração - HCFMUSP
São Paulo, , 05403-900
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Peter Lougheed Centre
Calgary, Alberta, T1Y 6J4
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University of Alberta
Edmonton, Alberta, T6G 2B7
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Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9
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London Health Sciences Centre
London, Ontario, N6A 5W9
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Centre Hospitalier de l'Université Laval
Sainte Foy, Quebec, G1V 4G5
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Vseobecna fakultni nemocnice v Praze
Prague, , 128 00
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Institut klinicke a experimentalni mediciny
Prague, , 140 00
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Universitätsklinikum Freiburg
Freiburg im Breisgau, Baden-Württemberg, 79106
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Universitatsklinkum Erlangen
Erlangen, Bayern, 91054
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Universität Greifswald
Greifswald, Mecklenburg-Vorpommern, 17475
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DRK Kliniken Berlin Westend
Berlin, , 14050
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Universitätsklinikum Carl Gustav Carus an der TU Dresden
Dresden, , 01307
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Universitätsklinikum Hamburg Eppendorf
Hamburg, , 20246
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Thorax Klinik
Heidelberg, , 69126
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Universitätsklinikum Köln
Köln, , 50937
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Hadassah University Hospital Ein Kerem
Jerusalem, , 91120
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Rabin Medical Center
Petah Tikva, , 49100
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Nippon Medical School Hospital
Tokyo, Bunkyo-ku, 113-8603
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Kitasato University Hospital
Sagamihara, Kanagawa, 252-0375
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Tohoku University Hospital
Sendai, Miyagi, 980-8574
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National Hospital Organization Okayama Medical Center
Okayama-shi, Okayama, 701-1192
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Chiba University Hospital
Chiba, , 260-8677
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Gunma University School of Medicine
Gunma, , 371-8510
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Kobe University Hospital
Kobe, , 6500017
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Nagoya Medical Center
Nagoya, , 460-0001
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Hokkaido University Hospital
Sapporo, , 0608648
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Kurume University Medical Center
Sendai-shi, , 980-8574
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National Cerebral and Cardiovascular Center
Suita, , 5658565
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Fujita Health University Hospital
Toyoake, , 470-1192
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Instituto Nacional de Cardiologia Dr. Ignacio Chavez
Ciudad de Mexico, Distrito Federal, 14080
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Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Mexico City, Distrito Federal, 14000
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Hospital Civil Fray Antonio Alcalde
Guadalajara, Jalisco, 44280
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Hospital Universitario Dr. Jose Eleuterio González
Monterrey, Nuevo Leon, 64460
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Unidad de Investigación Clínica En Medicina SC
Monterrey, Nuevo Leon, 64718
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Vrije Universiteit Amsterdam
Amsterdam, Noord-Holland, 1007 MB
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Angeles University Foundation Medical Center (AUFMC)
Angeles City, ,
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Mary Mediatrix Medical Center (MMMC)
Lipa, ,
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Makati Medical Center (MMC)
Makati, ,
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Philippine General Hospital (PGH)
Manila, ,
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Philippine Heart Center (PHC)
Quezon City, , 1100
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Hospital Universitario Marques de Valdecilla
Santander, Cantabria,
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Hospital Universitario Vall d'Hebron
Barcelona, , 08035
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Hospital de Gran Canaria Doctor Negrin
Las Palmas de Gran Canaria, , 35010
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Hospital Universitario 12 de Octubre
Madrid, , 28041
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Hospital Universitario Puerta de Hierro
Majadahonda, ,
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Hospital Virgen de La Salud
Toledo, , 45004
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Golden Jubilee National Hospital
Glasgow, , G81 4HX
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Royal Free Hospital
London, , NW3 2QG