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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03019185
Ethics application status
Date submitted
6/01/2017
Date registered
12/01/2017
Date last updated
20/12/2019

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 Cohort - 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 Cohort - 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 Cohort - 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
Increase in eGFR from baseline - To assess the increase in eGFR from baseline to week 12 (Phase 2) or week 48 (Phase 3) for patients receiving active drug, compared to patients receiving placebo.
Timepoint [1] 0 0
48 weeks
Secondary outcome [1] 0 0
Increase in eGFR from baseline following a 4-week drug treatment withdrawal period - To assess the change from baseline in eGFR in bardoxolone methyl-treated patients at Week 52 following a 4-week drug treatment withdrawal period.
Timepoint [1] 0 0
52 weeks
Secondary outcome [2] 0 0
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 - Safety will be assessed by monitoring adverse events, physical examinations and clinical laboratory test through 100 weeks.
Timepoint [2] 0 0
100 weeks

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
Gender
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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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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Alabama
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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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Paris
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Heidelberg
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Kawasaki
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Kobe
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Barcelona
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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 Pharmaceuticals, Inc.
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/show/NCT03019185
Trial related presentations / publications
Public notes

Contacts
Principal investigator
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Contact person for public queries
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Summary results
Other publications