Alport SyndromePhase 2/3CARDINALNCT03019185
A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome - CARDINAL
A Phase 2/3 study testing Bardoxolone Methyl in people with Alport Syndrome, run by Biogen at 63 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 60 years
- Conditions the study is for
- Alport Syndrome
- What is being tested?
- Bardoxolone Methyl
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 187 participants
- Where
- 63 sitesin 8 countries
- Study dates
- 2 Mar 2017to 30 Oct 2020
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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;
Who cannot join
- 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;
Show all 17Show fewer
- 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
Trial locations and contacts
63 sites in 8 countries.
63 sites in 8 countries
United States38 sites
Akron Nephrology Associates
Akron, Ohio, 44302
Akron Children's Hospital
Akron, Ohio, 44308
University of Michigan
Ann Arbor, Michigan, 48109
Emory University School of Medicine and Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Tufts Medical Center
Boston, Massachusetts, 02111
Boise Kidney & Hypertension Institute
Caldwell, Idaho, 83605
University of Cincinnati
Cincinnati, Ohio, 45220
Cleveland Clinic
Cleveland, Ohio, 44195
Renal Disease Research Institute
Dallas, Texas, 75235
Denver Nephrologists PC
Denver, Colorado, 80230
Duke University Medical Center
Durham, North Carolina, 27701
NorthShore University Health System
Evanston, Illinois, 60201
Nephrology Associates, PC
Flushing, New York, 11355
Hackensack Meridian School of Medicine
Hackensack, New Jersey, 07601
Southwest Houston Research
Houston, Texas, 77099
Children's Research Institute - The Children's Mercy Hospital
Kansas City, Missouri, 64108
Scripps Clinic, Nephrology
La Jolla, California, 92037
South Florida Research Institute
Lauderdale Lakes, Florida, 33313
Academic Medical Research Institute
Los Angeles, California, 90022
David Geffen School of Medicine at UCLA
Los Angeles, California, 90095
Boise Kidney & Hypertension Institute
Meridian, Idaho, 83642
University of Minnesota - Division of Pediatric Nephrology
Minneapolis, Minnesota, 55454
Columbia University Nephrology
New York, New York, 10032
South Carolina Nephrology & Hypertension Center, Inc
Orangeburg, South Carolina, 29118
Children's Hospital of Philadelphia (CHOP)
Philadelphia, Pennsylvania, 19104
Arizona Kidney Disease and Hypertension Research Services, PLLC
Phoenix, Arizona, 85308
University of Pittsburgh School of Medicine - Division of Pediatric Nephrology
Pittsburgh, Pennsylvania, 15224
Oregon Health & Science University
Portland, Oregon, 97239
The Warren Alpert Medical School of Brown University
Providence, Rhode Island, 02903
Biolab Research, LLC
Rockville, Maryland, 20852
University of Utah Health
Salt Lake City, Utah, 84132
Clinical Advancement Center
San Antonio, Texas, 78215
General Clinical Research Center - Parnassus
San Francisco, California, 94143
University of California San Francisco - Children's Renal Center
San Francisco, California, 94143
Washington University School of Medicine
St Louis, Missouri, 63110
Advanced Clinical Research
West Jordan, Utah, 84088
Brookview Hills Research Associates, PLLC
Winston-Salem, North Carolina, 27103
Japan10 sites
St Marianna University Hospital
Kawasaki
Kobe University Hospital
Kobe
Japanese Red Cross Nagoya Daini Hospital
Nagoya
JCHO Cyukyo Hospital
Nagoya
Kitano Hospital
Osaka
Saga University Hospital
Saga
Saitama Children's Medical Center
Saitama
JCHO Sendai Hospital
Sendai
Juntendo University Hospital
Tokyo
Tokyo Metropolitan Children's Medical Center
Tokyo
Australia5 sites
Royal Brisbane and Women's Hospital
Herston, Queensland, 2145
Melbourne Renal Research Group
Melbourne, VIC 3073
John Hunter Hospital
New Lambton Heights, NSW 2305
Sydney Children's Hospital
Sydney, NSW 2031
The Children's Hospital at Westmead
Westmead, NSW 2145
France3 sites
CHU Grenoble- Grenoble France
La Tronche, 38700
CHU Lyon-Hopital Edouard Herriot
Lyon, 69003
Hopital Necker-Universite Paris Descartes
Paris, 75015
Spain3 sites
Servicio de Nefrologia pediatrica
Barcelona, 119-08035
Fundacio Puigvert
Barcelona, 340-08025
Hospital Virgen de la Arrixaca
El Palmar, 30120
Germany2 sites
University of Medicine Gottingen
Göttingen, 37075
University Children's Hospital Heidelberg
Heidelberg, 69120
Puerto Rico1 site
Puerto Rico Clinical & Translational Research Center
Rio Piedras, 00935
About this study
Official title: A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome
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.
Read the 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.
- Conditions
- Alport Syndrome
- Being tested
- Placebo Oral Capsule, Bardoxolone Methyl
- Keywords
- Alport Syndrome, Bardoxolone methyl, CDDO-ME, RTA 402
- Medical subject headings
- Nephritis, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo Oral CapsuleDrug
Capsule containing an inert placebo
Bardoxolone MethylDrug
Also called RTA 402
Bardoxolone methyl dose escalated from 5 mg to a maximum of 20 or 30 mg, depending on baseline proteinuria status.
| Study group | Role | What they receive |
|---|---|---|
| Phase 2 Bardoxolone Methyl | Experimental | 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. Receives: Drug: Bardoxolone Methyl |
| Phase 3 Bardoxolone Methyl | Active comparator | 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. Receives: Drug: Bardoxolone Methyl |
| Phase 3 Placebo | Placebo comparator | Patients randomized to placebo will remain on placebo throughout the study, undergoing sham titration. Receives: Drug: Placebo Oral Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) After 12 Weeks of Treatment (Phase 2)
To assess the change in eGFR from baseline to week 12 (Phase 2). Estimated Glomerular filtration rate (eGFR) indicates how well the kidneys are filtering waste from the blood. The higher the eGFR number, the better the kidney function.
Measured: 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)
To assess the change in eGFR from baseline to week 48 (Phase 3). Estimated Glomerular filtration rate (eGFR) indicates how well the kidneys are filtering waste from the blood. The higher the eGFR number, the better the kidney function.
Measured: Baseline through 48 weeks after participant receives the first dose in the Phase 3 study
Change From Baseline in eGFR After 100 Weeks of Treatment (Phase 3)
To assess the change in eGFR from baseline to week 100 (Phase 3). Estimated Glomerular filtration rate (eGFR) indicates how well the kidneys are filtering waste from the blood. The higher the eGFR number, the better the kidney function.
Measured: Baseline through 100 weeks after participant receives the first dose in the Phase 3 study
Secondary outcomes (4)
Change From Baseline in eGFR After 48 Weeks of Treatment (Phase 2)
To assess the change from baseline in eGFR in bardoxolone methyl-treated patients at Week 48. Estimated Glomerular filtration rate (eGFR) indicates how well the kidneys are filtering waste from the blood. The higher the eGFR number, the better the kidney function.
Measured: Baseline through 48 weeks after participant receives the first dose in the Phase 2 study
Change From Baseline in eGFR After 100 Weeks of Treatment (Phase 2)
To assess the change from baseline in eGFR in bardoxolone methyl-treated patients at Week 100. Estimated Glomerular filtration rate (eGFR) indicates how well the kidneys are filtering waste from the blood. The higher the eGFR number, the better the kidney function.
Measured: Baseline through 100 weeks after participant receives the first dose in the Phase 2 study
Change From Baseline in eGFR at Week 52 Following a 4-week Drug Treatment Withdrawal Period (Phase 3)
To assess the change in eGFR from baseline to week 52 following a 4-week drug treatment withdrawal period (Phase 3). Estimated Glomerular filtration rate (eGFR) indicates how well the kidneys are filtering waste from the blood. The higher the eGFR number, the better the kidney function.
Measured: 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 at Week 104 Following a 4-week Drug Treatment Withdrawal Period (Phase 3)
To assess the change in eGFR from baseline to week 104 following a 4-week drug treatment withdrawal period (Phase 3). Estimated Glomerular filtration rate (eGFR) indicates how well the kidneys are filtering waste from the blood. The higher the eGFR number, the better the kidney function.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2017 (estimated)
- Study start2 Mar 2017
- Primary completion6 Oct 2020
- Study completion30 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Alport SyndromeStudies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 187 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03019185
- Sponsor's protocol ID
- RTA 402-C-1603
- Acronym
- CARDINAL
- Status last verified
- May 2025
- First submitted
- 6 Jan 2017
- Last updated
- 11 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
Publications
Warady BA, Pergola PE, Agarwal R, Andreoli S, Appel GB, Bangalore S, Block GA, Chapman AB, Chin MP, Gibson KL, Goldsberry A, Iijima K, Inker LA, Kashtan CE, Knebelmann B, Mariani LH, Meyer CJ, Nozu K, O'Grady M, Rheault MN, Silva AL, Stenvinkel P, Torra R, Chertow GM. Effects of Bardoxolone Methyl in Alport Syndrome. Clin J Am Soc Nephrol. 2022 Dec;17(12):1763-1774. doi: 10.2215/CJN.02400222. Epub 2022 Nov 21.
PubMed 36411058Chertow GM, Appel GB, Andreoli S, Bangalore S, Block GA, Chapman AB, Chin MP, Gibson KL, Goldsberry A, Iijima K, Inker LA, Knebelmann B, Mariani LH, Meyer CJ, Nozu K, O'Grady M, Silva AL, Stenvinkel P, Torra R, Warady BA, Pergola PE. Study Design and Baseline Characteristics of the CARDINAL Trial: A Phase 3 Study of Bardoxolone Methyl in Patients with Alport Syndrome. Am J Nephrol. 2021;52(3):180-189. doi: 10.1159/000513777. Epub 2021 Mar 31.
PubMed 33789284Kashtan CE, Gross O. Clinical practice recommendations for the diagnosis and management of Alport syndrome in children, adolescents, and young adults-an update for 2020. Pediatr Nephrol. 2021 Mar;36(3):711-719. doi: 10.1007/s00467-020-04819-6. Epub 2020 Nov 6.
PubMed 33159213
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome
- ClinicalTrials.gov ID
- NCT03019185
- Acronym / sponsor ID
- CARDINAL / RTA 402-C-1603
- Conditions
- Alport Syndrome
- Keywords
- Alport Syndrome, Bardoxolone methyl, CDDO-ME, RTA 402
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 187 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 2 Mar 2017 (actual)
- Primary completion
- 6 Oct 2020 (actual)
- Study completion
- 30 Oct 2020 (actual)
- First posted
- 12 Jan 2017 (estimated)
- Results
- Posted 11 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase 2 Bardoxolone Methyl | Experimental | Drug: Bardoxolone MethylPatients 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. |
| Phase 3 Bardoxolone Methyl | Active comparator | Drug: Bardoxolone MethylPatients 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. |
| Phase 3 Placebo | Placebo comparator | Drug: Placebo Oral CapsulePatients randomized to placebo will remain on placebo throughout the study, undergoing sham titration. |
Who may qualify
- Ages
- 12 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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;
Key exclusion criteria (17 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo Oral CapsuleCapsule containing an inert placebo | Drug | Phase 3 Placebo |
| Bardoxolone MethylAlso: RTA 402Bardoxolone methyl dose escalated from 5 mg to a maximum of 20 or 30 mg, depending on baseline proteinuria status. | Drug | Phase 2 Bardoxolone Methyl, Phase 3 Bardoxolone Methyl |
Primary outcome
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
To assess the change in eGFR from baseline to week 12 (Phase 2). Estimated Glomerular filtration rate (eGFR) indicates how well the kidneys are filtering waste from the blood. The higher the eGFR number, the better the kidney function.
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
To assess the change in eGFR from baseline to week 48 (Phase 3). Estimated Glomerular filtration rate (eGFR) indicates how well the kidneys are filtering waste from the blood. The higher the eGFR number, the better the kidney function.
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
To assess the change in eGFR from baseline to week 100 (Phase 3). Estimated Glomerular filtration rate (eGFR) indicates how well the kidneys are filtering waste from the blood. The higher the eGFR number, the better the kidney function.
4 secondary outcomes
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 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 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 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36411058Warady BA, Pergola PE, Agarwal R, Andreoli S, Appel GB, Bangalore S, Block GA, Chapman AB, Chin MP, Gibson KL, Goldsberry A, Iijima K, Inker LA, Kashtan CE, Knebelmann B, Mariani LH, Meyer CJ, Nozu K, O'Grady M, Rheault MN, Silva AL, Stenvinkel P, Torra R, Chertow GM. Effects of Bardoxolone Methyl in Alport Syndrome. Clin J Am Soc Nephrol. 2022 Dec;17(12):1763-1774. doi: 10.2215/CJN.02400222. Epub 2022 Nov 21.
- Derived from this study: PubMed 33789284Chertow GM, Appel GB, Andreoli S, Bangalore S, Block GA, Chapman AB, Chin MP, Gibson KL, Goldsberry A, Iijima K, Inker LA, Knebelmann B, Mariani LH, Meyer CJ, Nozu K, O'Grady M, Silva AL, Stenvinkel P, Torra R, Warady BA, Pergola PE. Study Design and Baseline Characteristics of the CARDINAL Trial: A Phase 3 Study of Bardoxolone Methyl in Patients with Alport Syndrome. Am J Nephrol. 2021;52(3):180-189. doi: 10.1159/000513777. Epub 2021 Mar 31.
- Derived from this study: PubMed 33159213Kashtan CE, Gross O. Clinical practice recommendations for the diagnosis and management of Alport syndrome in children, adolescents, and young adults-an update for 2020. Pediatr Nephrol. 2021 Mar;36(3):711-719. doi: 10.1007/s00467-020-04819-6. Epub 2020 Nov 6.
- Individual participant dataSharing planned: Yes. In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
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Alport Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
63 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Bardoxolone Methyl in people with Alport Syndrome, run by Biogen at 63 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 63 sites in United States, Japan, Australia, France, Spain and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03019185, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2025.