UMIN-CTR Clinical Trial

Basic information
Public title	A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients with Alport Syndrome
Acronym	CARDINAL
Scientific Title	A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients with Alport Syndrome
Scientific Title:Acronym	CARDINAL
Region	Japan North America Australia Europe

Condition
Condition	Alport Syndrome
Classification by specialty	Nephrology Pediatrics Urology
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	- To assess the change from baseline in estimated glomerular filtration rate (eGFR) in bardoxolone methyl-treated patients relative to placebo after 48 weeks of treatment. - To assess the safety of bardoxolone methyl relative to placebo after 48 weeks of treatment.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	The change from baseline in eGFR in bardoxolone methyl-treated patients relative to placebo at Week 48
Key secondary outcomes	The change from baseline in eGFR in bardoxolone methyl-treated patients relative to placebo at Week 52 following a 4-week drug treatment withdrawal period.

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Double blind -all involved are blinded
Control	Placebo
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Drug: Bardoxolone Methyl Bardoxolone methyl dose escalated from 5 mg to a maximum of 20 or 30 mg, depending on baseline proteinuria status. Dosing period is up to 2 years.
Interventions/Control_2	Drug: Placebo Oral Capsule Capsule containing an inert placebo is administrated up to 2 years.
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	12 years-old <=
Age-upper limit	70 years-old >=
Gender	Male and Female
Key inclusion criteria	1. Male and female patients from the age of 12 to 70 upon study consent 2. Diagnosis of Alport syndrome by genetic testing (documented mutation in a gene associated with Alport syndrome, including COL4A3, COL4A4, or COL4A5) or histologic assessment using electron microscopy 3. Screening eGFR (average of Screen A and Screen B eGFR values) is from 30 to 90 mL/min/1.73 m2. The two eGFR values collected at Screen A and Screen B visits used to determine eligibility must have a percent difference of 25% and under 4. Albumin to creatinine ratio (ACR) is 3500 mg/g and under at Screen B visit. Up to 50% of patients in the Phase 2 cohort and approximately 40% of patients enrolled in the Phase 3 cohort can have ACR of 301 to 3500 mg/g. Once enrollment of these patients is complete, the ACR inclusion criterion is 300 mg/g and under. 5. Patients receiving an angiotensin-converting enzyme (ACE) inhibitor and/or an angiotensin II receptor blocker (ARB) should be receiving the maximally tolerated labeled daily dose for at least 6 weeks prior to the Screen A visit. The dosage of ACE inhibitor and/or ARB should remain the same throughout the remainder of the study. Patients not currently taking an ACE inhibitor and/or ARB because they are not indicated or because of a medical contraindication may be eligible provided the patient has not taken an ACE inhibitor and/or ARB at least 8 weeks prior to the Screen A visit. 6. Adequate bone marrow reserve and organ function at the Screen A visit as follows: a. Hematologic: Absolute neutrophil count > 1500/microliter, platelets > 100000/microliter, hemoglobin of 9 g/dL and over b. Hepatic: Total bilirubin (TBL) of 1.5X the upper limit of normal (ULN) and under, ALT and AST of 1.5X ULN and under 7. Able to swallow capsules 8. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures 9. Evidence of a personally signed and dated informed consent document
Key exclusion criteria	1. Prior exposure to bardoxolone methyl 2. Ongoing chronic hemodialysis or peritoneal dialysis therapy 3. Renal transplant recipient 4. B-type natriuretic peptide (BNP) level > 200 pg/mL at Screen A visit 5. Uncontrolled diabetes (HbA1c > 11.0%) at Screen A visit 6. Acute dialysis or acute kidney injury within 12 weeks prior to Screen A visit or during Screening 7. Serum albumin < 3 g/dL at Screen A visit 8. History of clinically significant left-sided heart disease and/or clinically significant cardiac disease 9. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 160 mm Hg or sitting diastolic BP > 100 mm Hg at Screen A visit after a period of rest 10. Systolic BP < 90 mm Hg at Screen A visit after a period of rest 11. History of malignancy within 5 years prior to Screen A visit, with the exception of localized skin or cervical carcinomas 12. Systemic immunosuppression for more than 2 weeks, cumulatively, within the 12 weeks prior to randomization or anticipated need for immunosuppression during the study 13. Untreated or uncontrolled active bacterial, fungal, or viral infection 14. Participation in other interventional clinical studies within 30 days prior to Day 1 15. Unwilling to practice acceptable methods of birth control (both males who have partners of child-bearing 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 16. Women who are pregnant or breastfeeding 17. Known hypersensitivity to any component of the study drug
Target sample size	180

Research contact person
Name of lead principal investigator	1st name Colin Middle name Last name Meyer
Organization	Reata Pharmaceuticals, Inc
Division name	Product Development
Zip code	TX 75063
Address	2801 Gateway Drive, Suite 150 Irving, Texas, USA
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 Triton Square Office Tower Y 8F 1-8-11, Harumi, Cho-ku, Tokyo
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

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

IRB Contact (For public release)
Organization	Japan Community Health care Organization Sendai Hospital Institutional Review Board
Address	3-16-1 Tsutsumimachi, Aoba-ku, Sendai, Miyagi
Tel	022-275-3111
Email	keiko-yoshino@j-smo.com

Secondary IDs
Secondary IDs	YES
Study ID_1	NCT03019185
Org. issuing International ID_1	ClinicalTrials.gov
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	独立行政法人地域医療機能推進機構　仙台病院（宮城県） 埼玉県立小児医療センター（埼玉県） 順天堂大学医学部附属順天堂医院（東京都） 東京都立小児総合医療センター（東京都） 聖マリアンナ医科大学病院（神奈川県） 名古屋第二赤十字病院（愛知県） 独立行政法人地域医療機能推進機構　中京病院（愛知県） 公益財団法人 田附興風会 医学研究所　北野病院（大阪府） 神戸大学医学部附属病院（兵庫県） 佐賀大学医学部附属病院（佐賀県）

Other administrative information
Date of disclosure of the study information	2018 Year 05 Month 01 Day

Related information
URL releasing protocol
Publication of results	Published

Result
URL related to results and publications	https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-004395-22/results
Number of participants that the trial has enrolled	187
Results
Results date posted	2019 Year 05 Month 11 Day
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 11 Month 15 Day
Date of IRB	2017 Year 11 Month 06 Day
Anticipated trial start date	2018 Year 05 Month 01 Day
Last follow-up date	2020 Year 11 Month 30 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information	In Japan, a double-blind, randomized, and placebo-controlled study is under way, which is Phase 3 portion.

Management information
Registered date	2018 Year 05 Month 01 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=R000036991