UMIN-CTR Clinical Trial

Basic information
Public title	A Study of the Efficacy and Safety of Bardoxolone Methyl in Patients with Connective Tissue Disease-Associated Pulmonary Arterial Hypertension
Acronym	A Study of the Efficacy and Safety of Bardoxolone Methyl in Patients with Connective Tissue Disease-Associated Pulmonary Arterial Hypertension
Scientific Title	A Study of the Efficacy and Safety of Bardoxolone Methyl in Patients with Connective Tissue Disease-Associated Pulmonary Arterial Hypertension
Scientific Title:Acronym	A Study of the Efficacy and Safety of Bardoxolone Methyl in Patients with Connective Tissue Disease-Associated Pulmonary Arterial Hypertension
Region	Japan North America South America Australia Europe

Condition
Condition	Connective Tissue Disease-Associated Pulmonary Arterial Hypertension
Classification by specialty	Cardiology Pneumology Clinical immunology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To assess the efficacy of bardoxolone methyl relative to placebo.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase III

Assessment
Primary outcomes	Change from baseline in six-minute-walk distance (6MWD) relative to placebo at Week 24
Key secondary outcomes	*Improvement by at least one WHO functional class *Increase from baseline in 6MWD by at least 10% *Decrease from baseline in creatine kinase (as a surrogate biomarker for muscle injury and inflammation) by at least 10%

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Double blind -all involved are blinded
Control	Placebo
Stratification	YES
Dynamic allocation	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Drug: Bardoxolone Methyl Bardoxolone methyl dose escalated to a maximum of 10 mg. Dosing period is up to 6 months.
Interventions/Control_2	Drug: Placebo Oral Capsule Capsule containing an inert placebo is administrated up to 6 months.
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	18 years-old <=
Age-upper limit	75 years-old >=
Gender	Male and Female
Key inclusion criteria	1 Adult male and female patients 18 to 75 years of age upon study consent; 2 BMI 18.5 kgm2 3 Symptomatic pulmonary hypertension WHONYHA FC class II and III 4 WHO Group I PAH associated with connective tissue disease 5 Had a diagnostic right heart catheterization performed and documented within 36months prior to Day 1 that confirmed a diagnosis of PAH according to all the following criteria: a Mean pulmonary artery pressure 25 mm Hg (at rest) b Pulmonary capillary wedge pressure (PCWP)15 mm Hg c Pulmonary vascular resistance 240 dyn seccm5 or 3 mm Hg/liter (L)min 6 Has BNP level 400 pg/mL 7 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; 8 Has been receiving no more than two 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; 6 Has BNP level 400 pmL 7 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; 8 Has been receiving no more than two 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; etc
Key exclusion criteria	1 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; 2 Initiation of an exercise program for cardio-pulmonary rehabilitation within 90 days prior to Day1or planned initiation during the study; 3 Stopped receiving any PAH chronic therapy within 60 days prior to Day 1; 4 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; 5 Received intravenous or subcutaneous prostacyclin/prostacyclin analogues within 90 days prior to Day 1; 6 Received intravenous inotropes within 30 days prior to Day 1; 7 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 8 Has systolic BP 90 mm Hg during Screening after a period of rest 9 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: a Congenital or acquired valvular disease if clinically significant apart from tricuspid valvular insufficiency due to pulmonary hypertension; b Pericardial constriction; c Restrictive or congestive cardiomyopathy; d Left ventricular ejection fraction 40% per echocardiogram (ECHO) within 90 days of Day 1; e Symptomatic coronary artery disease within the last 3 years 10 Acutely decompensated heart failure within 30 days prior to Day 1, per investigator assessment 11 Has more than two of the following clinical risk factors for left ventricular diastolic dysfunction: a Age 65 years; b BMI 30 kgm2 c History of systemic hypertension; d History of type 2 diabetes; e History of atrial fibrillation etc
Target sample size	20

Research contact person
Name of lead principal investigator	1st name Colin Middle name Last name Meyer
Organization	Reata Pharmaceuticals
Division name	Product Development
Zip code	TX 75063
Address	2801 Gateway Drive, Suite 150 Irving
TEL	1-972-865-2202
Email	Colin.Meyer@reatapharma.com

Public contact
Name of contact person	1st name Yukiko Middle name Last name Hagihara
Organization	Labcorp Development Japan K.K.
Division name	Clinical Development Services
Zip code	104-6108
Address	Harumi Toriton Square Office Tower Y 8F 1-8-11, Harumi, Chuo-ku, Tokyo 104-6108
TEL	03-6837-9500
Homepage URL
Email	Yukiko.Hagihara@labcorp.com

Sponsor
Institute	Reata Pharmaceuticals, Inc.
Institute
Department

Funding Source
Organization	Reata Pharmaceuticals, Inc.
Organization
Division
Category of Funding Organization	Outside Japan
Nationality of Funding Organization	Unites States of America

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	National Hospital Organization Okayama Medical Center Institutional Review Board
Address	1711-1 Tamasu, Kita-ku, Okayama-shi, Okayama
Tel	086-294-9911
Email	chiken-crc@okayamamc.jp

Secondary IDs
Secondary IDs	YES
Study ID_1	US IND NUMBER: 119,235
Org. issuing International ID_1	US IND
Study ID_2	EUDRACT NUMBER: 2016-000196-24
Org. issuing International ID_2	EUDRACT
IND to MHLW	22-1359

Institutions
Institutions	北海道大学病院（北海道） 東北大学病院（宮城県） 群馬大学医学部附属病院（群馬県） 千葉大学医学部附属病院（千葉県） 日本医科大学付属病院（東京都） 北里大学病院（神奈川県） 藤田医科大学病院（愛知県） 独立行政法人国立病院機構　名古屋医療センター（愛知県） 国立研究開発法人　国立循環器病研究センター病院（大阪府） 独立行政法人国立病院機構　岡山医療センター（岡山県） 神戸大学医学部付属病院（兵庫県） 久留米大学医学部附属病院（福岡県）

Other administrative information
Date of disclosure of the study information	2016 Year 12 Month 07 Day

Related information
URL releasing protocol
Publication of results	Published

Result
URL related to results and publications	https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-000196-24/results
Number of participants that the trial has enrolled	202
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Main results already published
Date of protocol fixation	2016 Year 01 Month 27 Day
Date of IRB	2016 Year 07 Month 29 Day
Anticipated trial start date	2016 Year 09 Month 01 Day
Last follow-up date	2020 Year 06 Month 12 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2016 Year 12 Month 06 Day
Last modified on	2022 Year 03 Month 11 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028933