NCT03019185: CARDINAL

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

Completed Phase 2, PHASE3 Results posted Last updated 11 June 2025

What this trial tests

Phase 2, PHASE3 trial testing Placebo Oral Capsule in Alport Syndrome in 187 participants. Completed in 30 October 2020.

Timeline

2 March 2017

Primary endpoint
6 October 2020

30 October 2020

Quick facts

Lead sponsor	Biogen
Phase	Phase 2, PHASE3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	187
Start date	2 March 2017
Primary completion	6 October 2020
Estimated completion	30 October 2020
Sites	63 locations across France, Japan, United Kingdom, Germany, Puerto Rico, Australia, United States, Spain

Drugs / interventions tested

• Placebo Oral Capsule
• Bardoxolone Methyl — full drug profile →

Conditions studied

• Alport Syndrome — all drugs for Alport Syndrome →

Sponsor

Biogen — full company profile →

Who can join

Adults 12 to 60, any sex, with Alport Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) After 12 Weeks of Treatment (Phase 2) Primary · 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.

Group	Value	95% CI
Phase 2 Bardoxolone Methyl	13.37	± 1.4111

Change From Baseline in eGFR After 48 Weeks of Treatment (Phase 3) Primary · 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.

Group	Value	95% CI
Phase 3 Placebo	-4.77	± 1.248
Phase 3 Bardoxolone Methyl	4.71	± 1.307

Change From Baseline in eGFR After 100 Weeks of Treatment (Phase 3) Primary · 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.

Group	Value	95% CI
Phase 3 Placebo	-8.45	± 1.478
Phase 3 Bardoxolone Methyl	-0.81	± 1.556

Change From Baseline in eGFR After 48 Weeks of Treatment (Phase 2) Secondary · Baseline through 48 weeks after participant receives the first dose in the Phase 2 study

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.

Group	Value	95% CI
Phase 2 Bardoxolone Methyl	7.4	± 1.9451

Change From Baseline in eGFR After 100 Weeks of Treatment (Phase 2) Secondary · Baseline through 100 weeks after participant receives the first dose in the Phase 2 study

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.

Group	Value	95% CI
Phase 2 Bardoxolone Methyl	4.28	± 1.7484

Change From Baseline in eGFR at Week 52 Following a 4-week Drug Treatment Withdrawal Period (Phase 3) Secondary · 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)

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.

Group	Value	95% CI
Phase 3 Placebo	-6.08	± 1.243
Phase 3 Bardoxolone Methyl	-0.99	± 1.253

Change From Baseline in eGFR at Week 104 Following a 4-week Drug Treatment Withdrawal Period (Phase 3) Secondary · 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)

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.

Group	Value	95% CI
Phase 3 Placebo	-8.84	± 1.353
Phase 3 Bardoxolone Methyl	-4.52	± 1.395

Adverse events — posted to ClinicalTrials.gov

Time frame: 104 weeks. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase 2 Bardoxolone Methyl

Serious: 6/30 (20%)

Deaths: 0/30

Phase 3 Placebo

Serious: 15/80 (19%)

Deaths: 0/80

Phase 3 Bardoxolone Methyl

Serious: 8/77 (10%)

Deaths: 0/77

Serious adverse events (29 terms)

Reaction	System	Phase 2 Bardoxolone Methyl	Phase 3 Placebo	Phase 3 Bardoxolone Methyl
End stage renal disease	Renal and urinary disorders	—	—	—
Pneumonia	Infections and infestations	—	—	—
Ileus	Gastrointestinal disorders	—	—	—
Asthenia	General disorders	—	—	—
Non-cardiac chest pain	General disorders	—	—	—
Oedema peripheral	General disorders	—	—	—
Anaphylactic reaction	Immune system disorders	—	—	—
Empyema	Infections and infestations	—	—	—
Pyelonephritis	Infections and infestations	—	—	—
Animal bite	Injury, poisoning and procedural complications	—	—	—
Clavicle fracture	Injury, poisoning and procedural complications	—	—	—
Laceration	Injury, poisoning and procedural complications	—	—	—
Rib fracture	Injury, poisoning and procedural complications	—	—	—
Scapula fracture	Injury, poisoning and procedural complications	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—
Carcinoid tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Carcinoid tumour pulmonary	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Colon adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Ischaemic stroke	Nervous system disorders	—	—	—
Status migrainosus	Nervous system disorders	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—
Proteinuria	Renal and urinary disorders	—	—	—
Ovarian mass	Reproductive system and breast disorders	—	—	—

Other adverse events (194 terms — click to expand)

Reaction	System	Phase 2 Bardoxolone Methyl	Phase 3 Placebo	Phase 3 Bardoxolone Methyl
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—
Headache	Nervous system disorders	—	—	—
Fatigue	General disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Oedema peripheral	General disorders	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Dizziness	Nervous system disorders	—	—	—
Brain natriuretic peptide increased	Investigations	—	—	—
Hyperkalaemia	Metabolism and nutrition disorders	—	—	—
Weight decreased	Investigations	—	—	—
Blood creatine phosphokinase increased	Investigations	—	—	—
Blood creatinine increased	Investigations	—	—	—
Urine albumin/creatinine ratio increased	Investigations	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Hypertension	Vascular disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Influenza	Infections and infestations	—	—	—
Sinusitis	Infections and infestations	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—
Proteinuria	Renal and urinary disorders	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—
Non-cardiac chest pain	General disorders	—	—	—
Weight increased	Investigations	—	—	—
Gout	Metabolism and nutrition disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—
Urinary tract infection	Infections and infestations	—	—	—
N-terminal prohormone brain natriuretic peptide increased	Investigations	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—
Malaise	General disorders	—	—	—

Most-reported serious reactions: End stage renal disease, Pneumonia, Ileus, Asthenia, Non-cardiac chest pain, Oedema peripheral, Anaphylactic reaction, Empyema.

Data from ClinicalTrials.gov NCT03019185 adverse events section.

Sponsor's own 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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Kidney fibrosis: from mechanisms to therapeutic medicines.
   Huang R, Fu P, Ma L. · · 2023 · cited 453× · PMID 36932062 · DOI 10.1038/s41392-023-01379-7
2. Activators and Inhibitors of NRF2: A Review of Their Potential for Clinical Development.
   Robledinos-Antón N, Fernández-Ginés R, Manda G, Cuadrado A. · · 2019 · cited 443× · PMID 31396308 · DOI 10.1155/2019/9372182
3. Signaling pathways of chronic kidney diseases, implications for therapeutics.
   Yuan Q, Tang B, Zhang C. · · 2022 · cited 303× · PMID 35680856 · DOI 10.1038/s41392-022-01036-5
4. Reactive Oxygen Species and Redox Signaling in Chronic Kidney Disease.
   Irazabal MV, Torres VE. · · 2020 · cited 240× · PMID 32481548 · DOI 10.3390/cells9061342
5. Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy.
   Rayego-Mateos S, Morgado-Pascual JL, Opazo-Ríos L, Guerrero-Hue M, et al · · 2020 · cited 237× · PMID 32471207 · DOI 10.3390/ijms21113798
6. Can Activation of NRF2 Be a Strategy against COVID-19?
   Cuadrado A, Pajares M, Benito C, Jiménez-Villegas J, et al · · 2020 · cited 168× · PMID 32711925 · DOI 10.1016/j.tips.2020.07.003
7. The glomerular filtration barrier: a structural target for novel kidney therapies.
   Daehn IS, Duffield JS. · · 2021 · cited 160× · PMID 34262140 · DOI 10.1038/s41573-021-00242-0
8. Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study.
   Chin MP, Bakris GL, Block GA, Chertow GM, et al · · 2018 · cited 131× · PMID 29402767 · DOI 10.1159/000486398