A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome - CARDINAL

• Register: ClinicalTrials.gov
• Last refreshed on: 12 February 2024
• Main ID: NCT03019185
• Date of registration: 06/01/2017
• Prospective Registration: Yes
• Primary sponsor: Reata, a wholly owned subsidiary of Biogen
• Public title: A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome - CARDINAL CARDINAL
• Scientific title: A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome
• Date of first enrolment: March 2, 2017
• Target sample size: 187
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03019185
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2/Phase 3

Countries of recruitment

Australia, Canada, France, Germany, Japan, Puerto Rico, Spain, United Kingdom, United States

Key inclusion & exclusion criteria

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;

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



Age minimum: 12 Years
Age maximum: 60 Years
Gender: All

Health Condition(s) or Problem(s) studied

Alport Syndrome

Intervention(s)

Drug: Bardoxolone Methyl

Drug: Placebo Oral Capsule

Primary Outcome(s)

Change From Baseline in eGFR After 100 Weeks of Treatment (Phase 3) [Time Frame: Baseline through 100 weeks after participant receives the first dose in the Phase 3 study]

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) After 12 Weeks of Treatment (Phase 2) [Time Frame: Baseline through 12 weeks after participant receives the first dose in the Phase 2 study]

Change From Baseline in eGFR After 48 Weeks of Treatment (Phase 3) [Time Frame: Baseline through 48 weeks after participant receives the first dose in the Phase 3 study]

Secondary Outcome(s)

Change From Baseline in eGFR at Week 52 Following a 4-week Drug Treatment Withdrawal Period (Phase 3) [Time Frame: 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)]

Change From Baseline in eGFR After 100 Weeks of Treatment (Phase 2) [Time Frame: Baseline through 100 weeks after participant receives the first dose in the Phase 2 study]

Change From Baseline in eGFR After 48 Weeks of Treatment (Phase 2) [Time Frame: Baseline through 48 weeks after participant receives the first dose in the Phase 2 study]

Change From Baseline in eGFR at Week 104 Following a 4-week Drug Treatment Withdrawal Period (Phase 3) [Time Frame: 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)]

Secondary ID(s)

RTA 402-C-1603

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 11/10/2023
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03019185