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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03019185




Registration number
NCT03019185
Ethics application status
Date submitted
6/01/2017
Date registered
12/01/2017
Date last updated
2/02/2024

Titles & IDs
Public title
A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome - CARDINAL
Scientific title
A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome
Secondary ID [1] 0 0
RTA 402-C-1603
Universal Trial Number (UTN)
Trial acronym
CARDINAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alport Syndrome 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Renal and Urogenital 0 0 0 0
Kidney disease
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo Oral Capsule
Treatment: Drugs - Bardoxolone Methyl

Experimental: Phase 2 Bardoxolone Methyl - Patients in the Phase 2 cohort will receive bardoxolone methyl throughout the study. Patients with baseline ACR = 300 mg/g will be titrated to a maximum dose of 20 mg, and patients with baseline ACR > 300 mg/g will be titrated to a maximum dose of 30 mg. Adult patients (= 18 years of age) receiving bardoxolone methyl will start with once-daily dosing at 5 mg and will dose-escalate to 10 mg at Week 2, to 20 mg at Week 4, and then to 30 mg at Week 6 (only if baseline ACR >300 mg/g) unless contraindicated clinically and approved by the medical monitor. Patients under the age of 18 receiving bardoxolone methyl will start 5 mg every other day during the first week and begin once-daily dosing with 5 mg during the second week of the study, and then continue with once-daily dosing following the same aforementioned dose titration scheme based on baseline ACR at Weeks 2, 4, and 6.

Active Comparator: Phase 3 Bardoxolone Methyl - Patients with baseline ACR = 300 mg/g will be titrated to a maximum dose of 20 mg, and patients with baseline ACR > 300 mg/g will be titrated to a maximum dose of 30 mg. Adult patients (= 18 years of age) receiving bardoxolone methyl will start with once-daily dosing at 5 mg and will dose-escalate to 10 mg at Week 2, to 20 mg at Week 4, and then to 30 mg at Week 6 (only if baseline ACR >300 mg/g) unless contraindicated clinically and approved by the medical monitor. Patients under the age of 18 receiving bardoxolone methyl will start 5 mg every other day during the first week and begin once-daily dosing with 5 mg during the second week of the study, and then continue with once-daily dosing following the same aforementioned dose titration scheme based on baseline ACR at Weeks 2, 4, and 6.

Placebo Comparator: Phase 3 Placebo - Patients randomized to placebo will remain on placebo throughout the study, undergoing sham titration.


Treatment: Drugs: Placebo Oral Capsule
Capsule containing an inert placebo

Treatment: Drugs: Bardoxolone Methyl
Bardoxolone methyl dose escalated from 5 mg to a maximum of 20 or 30 mg, depending on baseline proteinuria status.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) After 12 Weeks of Treatment (Phase 2)
Timepoint [1] 0 0
Baseline through 12 weeks after participant receives the first dose in the Phase 2 study
Primary outcome [2] 0 0
Change From Baseline in eGFR After 48 Weeks of Treatment (Phase 3)
Timepoint [2] 0 0
Baseline through 48 weeks after participant receives the first dose in the Phase 3 study
Primary outcome [3] 0 0
Change From Baseline in eGFR After 100 Weeks of Treatment (Phase 3)
Timepoint [3] 0 0
Baseline through 100 weeks after participant receives the first dose in the Phase 3 study
Secondary outcome [1] 0 0
Change From Baseline in eGFR After 48 Weeks of Treatment (Phase 2)
Timepoint [1] 0 0
Baseline through 48 weeks after participant receives the first dose in the Phase 2 study
Secondary outcome [2] 0 0
Change From Baseline in eGFR After 100 Weeks of Treatment (Phase 2)
Timepoint [2] 0 0
Baseline through 100 weeks after participant receives the first dose in the Phase 2 study
Secondary outcome [3] 0 0
Change From Baseline in eGFR at Week 52 Following a 4-week Drug Treatment Withdrawal Period (Phase 3)
Timepoint [3] 0 0
Baseline through 52 weeks after participant receives the first dose in the Phase 3 study (or 4 weeks after last dose for patients who discontinued early in the first year)
Secondary outcome [4] 0 0
Change From Baseline in eGFR at Week 104 Following a 4-week Drug Treatment Withdrawal Period (Phase 3)
Timepoint [4] 0 0
Baseline through 104 weeks after participant receives the first dose in the Phase 3 study (or 4 weeks after last dose for patients who discontinued early in the second year)

Eligibility
Key inclusion criteria
- Male and female patients 12 = age = 60 upon study consent;

- 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;

- Screening eGFR = 30 and = 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 =
25%;

- Albumin to creatinine ratio (ACR) = 3500 mg/g at Screen B visit;

- If receiving an angiotensin-converting enzyme (ACE) inhibitor and/or an angiotensin II
receptor blocker (ARB), the medications must remain the same for at least 6 weeks
prior to the Screen A visit and during Screening. The dosage of ACE inhibitor and/or
ARB must also be stable for 2 weeks prior to the Screen A visit and remain the same
through Day 1 (i.e., no change in dosage or medication). Patients not taking an ACE
inhibitor and/or ARB because of a medical contraindication must have discontinued
treatment at least 8 weeks prior to the Screen A visit;

- Adequate bone marrow reserve and organ function at the Screen A visit

- Able to swallow capsules;

- Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
and other study procedures;
Minimum age
12 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior exposure to bardoxolone methyl;

- Ongoing chronic hemodialysis or peritoneal dialysis therapy;

- Renal transplant recipient;

- B-type natriuretic peptide (BNP) level > 200 pg/mL at Screen A visit;

- Uncontrolled diabetes (HbA1c > 11.0%) at Screen A visit;

- Acute dialysis or acute kidney injury within 12 weeks prior to Screen A visit or
during Screening;

- Serum albumin < 3 g/dL at Screen A visit;

- History of clinically significant left-sided heart disease and/or clinically
significant cardiac disease, including but not limited to any of the following:

- 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;

- Systolic BP < 90 mm Hg at Screen A visit after a period of rest;

- History of malignancy within 5 years prior to Screen A visit, with the exception of
localized skin or cervical carcinomas;

- Systemic immunosuppression for more than 2 weeks, cumulatively, within the 12 weeks
prior to randomization or anticipated need for immunosuppression during the study;

- Untreated or uncontrolled active bacterial, fungal, or viral infection;

- Participation in other interventional clinical studies within 30 days prior to Day 1;

- 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;

- Women who are pregnant or breastfeeding;

- Known hypersensitivity to any component of the study drug

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/03/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/10/2020
Sample size
Target
Accrual to date
Final
187
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [2] 0 0
Melbourne Renal Research Group - Melbourne
Recruitment hospital [3] 0 0
John Hunter Hospital - New Lambton Heights
Recruitment hospital [4] 0 0
Sydney Children's Hospital - Sydney
Recruitment hospital [5] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Herston
Recruitment postcode(s) [2] 0 0
VIC 3073 - Melbourne
Recruitment postcode(s) [3] 0 0
NSW 2305 - New Lambton Heights
Recruitment postcode(s) [4] 0 0
NSW 2031 - Sydney
Recruitment postcode(s) [5] 0 0
NSW 2145 - Westmead
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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California
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Colorado
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Florida
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Georgia
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Idaho
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Illinois
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Missouri
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New Jersey
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New York
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North Carolina
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Ohio
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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Texas
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Utah
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France
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La Tronche
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France
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Lyon
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France
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Paris
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Germany
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Göttingen
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Germany
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Heidelberg
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Japan
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Kawasaki
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Japan
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Kobe
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Japan
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Nagoya
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Japan
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Osaka
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Japan
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Saga
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Japan
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Saitama
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Japan
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Sendai
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Japan
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Tokyo
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Puerto Rico
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Rio Piedras
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Spain
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Barcelona
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Spain
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El Palmar
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United Kingdom
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London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Reata, a wholly owned subsidiary of Biogen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This international, multi-center, Phase 2/3 trial will study the safety, tolerability, and
efficacy of bardoxolone methyl in qualified patients with Alport syndrome. The Phase 2
portion of the trial will be open-label and enroll up to 30 patients. The Phase 3 portion of
the trial will be double-blind, randomized, placebo-controlled and will enroll up to 180
patients.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03019185
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
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Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03019185