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Trial record 1 of 2 for:    Alport syndrome reata
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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 : Active, not recruiting
First Posted : January 12, 2017
Last Update Posted : December 20, 2019
Sponsor:
Information provided by (Responsible Party):
Reata Pharmaceuticals, Inc.

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.

Condition or disease Intervention/treatment Phase
Alport Syndrome Drug: Placebo Oral Capsule Drug: Bardoxolone Methyl Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 187 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome
Actual Study Start Date : March 2, 2017
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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

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.
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

Placebo Comparator: Phase 3 Placebo Cohort
Patients randomized to placebo will remain on placebo throughout the study, undergoing sham titration.
Drug: Placebo Oral Capsule
Capsule containing an inert placebo




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03019185


Locations
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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Arizona Kidney Disease and Hypertension Research Services, PLLC
Phoenix, Arizona, United States, 85308
United States, California
Scripps Clinic, Nephrology
La Jolla, California, United States, 92037
Academic Medical Research Institute
Los Angeles, California, United States, 90022
David Geffen School of Medicine at UCLA
Los Angeles, California, United States, 90095
General Clinical Research Center - Parnassus
San Francisco, California, United States, 94143
University of California San Francisco - Children's Renal Center
San Francisco, California, United States, 94143
United States, Colorado
Denver Nephrologists PC
Denver, Colorado, United States, 80230
United States, Florida
South Florida Research Institute
Lauderdale Lakes, Florida, United States, 33313
United States, Georgia
Emory University School of Medicine and Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30322
United States, Idaho
Boise Kidney & Hypertension Institute
Caldwell, Idaho, United States, 83605
Boise Kidney & Hypertension Institute
Meridian, Idaho, United States, 83642
United States, Illinois
NorthShore University Health System
Evanston, Illinois, United States, 60201
United States, Maryland
Biolab Research, LLC
Rockville, Maryland, United States, 20852
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
University of Minnesota - Division of Pediatric Nephrology
Minneapolis, Minnesota, United States, 55454
United States, Missouri
Children's Research Institute - The Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Hackensack Meridian School of Medicine
Hackensack, New Jersey, United States, 07601
United States, New York
Nephrology Associates, PC
Flushing, New York, United States, 11355
Columbia University Nephrology
New York, New York, United States, 10032
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27701
Brookview Hills Research Associates, PLLC
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
Akron Nephrology Associates
Akron, Ohio, United States, 44302
Akron Children's Hospital
Akron, Ohio, United States, 44308
University of Cincinnati
Cincinnati, Ohio, United States, 45220
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children's Hospital of Philadelphia (CHOP)
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh School of Medicine - Division of Pediatric Nephrology
Pittsburgh, Pennsylvania, United States, 15224
United States, Rhode Island
The Warren Alpert Medical School of Brown University
Providence, Rhode Island, United States, 02903
United States, South Carolina
South Carolina Nephrology & Hypertension Center, Inc
Orangeburg, South Carolina, United States, 29118
United States, Texas
Renal Disease Research Institute
Dallas, Texas, United States, 75235
Southwest Houston Research
Houston, Texas, United States, 77099
Clinical Advancement Center
San Antonio, Texas, United States, 78215
United States, Utah
University of Utah Health
Salt Lake City, Utah, United States, 84132
Advanced Clinical Research
West Jordan, Utah, United States, 84088
Australia, Queensland
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia, 2145
Australia
Melbourne Renal Research Group
Melbourne, Australia, VIC 3073
John Hunter Hospital
New Lambton Heights, Australia, NSW 2305
Sydney Children's Hospital
Sydney, Australia, NSW 2031
The Children's Hospital at Westmead
Westmead, Australia, NSW 2145
France
CHU Grenoble- Grenoble France
La Tronche, France, 38700
CHU Lyon-Hopital Edouard Herriot
Lyon, France, 69003
Hopital Necker-Universite Paris Descartes
Paris, France, 75015
Germany
University of Medicine Gottingen
Göttingen, Germany, 37075
University Children's Hospital Heidelberg
Heidelberg, Germany, 69120
Japan
St Marianna University Hospital
Kawasaki, Japan
Kobe University Hospital
Kobe, Japan
Japanese Red Cross Nagoya Daini Hospital
Nagoya, Japan
JCHO Cyukyo Hospital
Nagoya, Japan
Kitano Hospital
Osaka, Japan
Saga University Hospital
Saga, Japan
Saitama Children's Medical Center
Saitama, Japan
JCHO Sendai Hospital
Sendai, Japan
Juntendo University Hospital
Tokyo, Japan
Tokyo Metropolitan Children`s Medical Center
Tokyo, Japan
Puerto Rico
Puerto Rico Clinical & Translational Research Center
Rio Piedras, Puerto Rico, 00935
Spain
Servicio de Nefrologia pediatrica
Barcelona, Spain, 119-08035
Fundacio Puigvert
Barcelona, Spain, 340-08025
Hospital Virgen de la Arrixaca
El Palmar, Spain, 30120
United Kingdom
Royal Free Hospital
London, United Kingdom, NW3 2QG
Sponsors and Collaborators
Reata Pharmaceuticals, Inc.
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Responsible Party: Reata Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03019185    
Other Study ID Numbers: RTA 402-C-1603
First Posted: January 12, 2017    Key Record Dates
Last Update Posted: December 20, 2019
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Reata Pharmaceuticals, Inc.:
Alport Syndrome
Bardoxolone methyl
CDDO-ME
RTA 402
Additional relevant MeSH terms:
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Syndrome
Nephritis, Hereditary
Disease
Pathologic Processes
Urogenital Abnormalities
Nephritis
Kidney Diseases
Urologic Diseases
Congenital Abnormalities
Collagen Diseases
Connective Tissue Diseases