Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03019185
Recruitment Status : Completed
First Posted : January 12, 2017
Last Update Posted : September 28, 2021
Sponsor:
Information provided by (Responsible Party):
Reata Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE January 6, 2017
First Posted Date  ICMJE January 12, 2017
Last Update Posted Date September 28, 2021
Actual Study Start Date  ICMJE March 2, 2017
Actual Primary Completion Date October 6, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2017)
Increase in eGFR from baseline [ Time Frame: 48 weeks ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 10, 2017)
  • Increase in eGFR from baseline following a 4-week drug treatment withdrawal period [ Time Frame: 52 weeks ]
    To assess the change from baseline in eGFR in bardoxolone methyl-treated patients at Week 52 following a 4-week drug treatment withdrawal period.
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 100 weeks ]
    Safety will be assessed by monitoring adverse events, physical examinations and clinical laboratory test through 100 weeks.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome - CARDINAL
Official Title  ICMJE A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome
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.
Detailed Description

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.

Patients in the Phase 2 cohort will receive bardoxolone methyl throughout the study. Patients in the Phase 3 cohort will be randomized 1:1 to either bardoxolone methyl or placebo and randomization will be stratified by baseline albumin to creatinine ratio (ACR). Patients randomized to placebo will remain on placebo throughout the study, undergoing sham titration.

All patients in the study will follow the same visit and assessment schedule. Following randomization on Day 1, patients will be scheduled to be assessed during treatment at Weeks 1, 2, 4, 6, 8, 12, 24, 36, 48, 52, 64, 76, 88, 100, and 104 and by telephone contact on Days 3, 10, 21, 31, 38, and 45. Patients will not receive study drug during a 4-week withdrawal period between Weeks 48 and 52. They will re-start treatment at Week 52 at the same dose they received at Week 48 and will continue study drug treatment through Week 100. Patients will also be scheduled to be assessed at an in person follow up visit at Week 104, four weeks after the end of treatment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Alport Syndrome
Intervention  ICMJE
  • Drug: Placebo Oral Capsule
    Capsule containing an inert placebo
  • Drug: Bardoxolone Methyl
    Bardoxolone methyl dose escalated from 5 mg to a maximum of 20 or 30 mg, depending on baseline proteinuria status.
    Other Name: RTA 402
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Bardoxolone Methyl
  • 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.
    Intervention: Drug: Bardoxolone Methyl
  • Placebo Comparator: Phase 3 Placebo Cohort
    Patients randomized to placebo will remain on placebo throughout the study, undergoing sham titration.
    Intervention: Drug: Placebo Oral Capsule
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 12, 2018)
187
Original Estimated Enrollment  ICMJE
 (submitted: January 10, 2017)
210
Actual Study Completion Date  ICMJE October 30, 2020
Actual Primary Completion Date October 6, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 60 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   France,   Germany,   Japan,   Puerto Rico,   Spain,   United Kingdom,   United States
Removed Location Countries Canada
 
Administrative Information
NCT Number  ICMJE NCT03019185
Other Study ID Numbers  ICMJE RTA 402-C-1603
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Reata Pharmaceuticals, Inc.
Study Sponsor  ICMJE Reata Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Reata Pharmaceuticals, Inc.
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP