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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03019185
Ethics application status
Date submitted
6/01/2017
Date registered
12/01/2017

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
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
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arizona
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United States of America
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California
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United States of America
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Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
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United States of America
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Idaho
Country [8] 0 0
United States of America
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Illinois
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United States of America
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Maryland
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United States of America
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Massachusetts
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Michigan
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Minnesota
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Missouri
Country [14] 0 0
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New Jersey
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New York
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North Carolina
Country [17] 0 0
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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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United States of America
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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
State/province [40] 0 0
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
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/


What supporting documents are/will be available?

TypeOther DetailsAttachment
Study protocol Study Protocol: US Protocol https://cdn.clinicaltrials.gov/large-docs/85/NCT03019185/Prot_000.pdf
Study protocol Study Protocol: US Protocol Addendum https://cdn.clinicaltrials.gov/large-docs/85/NCT03019185/Prot_001.pdf
Study protocol Study Protocol: Europe Protocol https://cdn.clinicaltrials.gov/large-docs/85/NCT03019185/Prot_002.pdf
Study protocol Study Protocol: Germany Protocol https://cdn.clinicaltrials.gov/large-docs/85/NCT03019185/Prot_003.pdf
Study protocol Study Protocol: France Spain UK Protocol https://cdn.clinicaltrials.gov/large-docs/85/NCT03019185/Prot_004.pdf
Study protocol Study Protocol: France Spain UK Protocol Addendum https://cdn.clinicaltrials.gov/large-docs/85/NCT03019185/Prot_005.pdf
Statistical analysis plan Statistical Analysis Plan: Phase 2 SAP https://cdn.clinicaltrials.gov/large-docs/85/NCT03019185/SAP_006.pdf
Statistical analysis plan Statistical Analysis Plan: Phase 3 SAP https://cdn.clinicaltrials.gov/large-docs/85/NCT03019185/SAP_007.pdf



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03019185