clinical study to evaluate the efficacy and safety of a new drug (Bardoxolone methyl) in the treatment of subjects with Alport syndrome

Phase 1

• Conditions: Alport Syndrome; MedDRA version: 20.0Level: PTClassification code 10001843Term: Alport's syndromeSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2016-004395-22-ES
• Lead Sponsor: Reata Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-11-07
• Study Completion: 2020-10-30
• Last Update Posted: 19 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 187

Inclusion Criteria

1. Male and female patients 18 = age = 60 upon study consent;
2. 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;
3. Screening eGFR (average of Screen A and Screen B eGFR values) = 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%;
4. Albumin to creatinine ratio (ACR) = 3500 mg/g at Screen B visit;
5. Receiving an angiotensin converting enzyme (ACE) inhibitor and/or an angiotensin II receptor blocker (ARB), at the maximally tolerated labeled daily dose (MTLDD), as defined in Section 9.1.7, for at least 6 weeks prior to the Screen A visit. The dosage of ACE inhibitor and/or ARB should remain the same throughout the remainder of the study (i.e., no change in dosage or medication), and any potential changes should be discussed with the medical monitor. Patients not taking an ACE inhibitor and/or ARB because of a medical contraindication may be eligible if they have discontinued treatment at least 8 weeks prior to the Screen A visit (these patients must be discussed with medical monitor prior to enrollment);
6. Adequate bone marrow reserve and organ function at the Screen A visit as follows:
a. Hematologic: Absolute neutrophil count > 1.5 x 109/L, platelets > 100 x 109/L,
hemoglobin (Hgb) = 9 g/dL;
b. Hepatic: Total bilirubin (TBL) = 1.5X the upper limit of normal (ULN), alanine
aminotransferase (ALT) and aspartate aminotransferase (AST) = 1.5X ULN;
7. Able to swallow capsules;
8. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;
9. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study prior to initiation of any patient-mandated procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Prior exposure to bardoxolone methyl;
2. Ongoing chronic hemodialysis or peritoneal dialysis therapy;
3. Renal transplant recipient;
4. B-type natriuretic peptide (BNP) level >200 pg/mL at Screen A visit;
5. Uncontrolled diabetes (HbA1c >11.0%) at Screen A visit;
6. Acute dialysis or acute kidney injury within 12 weeks prior to Screen A visit or during Screening;
7. Serum albumin < 3 g/dL at Screen A visit;
8. History of clinically significant left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following:
a. Clinically significant congenital or acquired valvular disease;
b. Left ventricular ejection fraction < 40% (based on echocardiogram performed at Screen A visit or within 6 months prior to Day 1);
c. Pericardial constriction (based on echocardiogram performed at Screen A visit or within 6 months prior to Day 1);
d. Restrictive or congestive cardiomyopathy (based on echocardiogram performed at Screen A visit or within 6 months prior to Day 1);
e. Symptomatic coronary disease (prior myocardial infarction, percutaneous
coronary intervention, coronary artery bypass graft surgery, or angina);
f. History of hospitalization for heart failure;
g. Cardiac insufficiency, defined as New York Heart Association Class >2;
h. History of atrial fibrillation;
i. History of unstable arrhythmias;
9. 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;
10. Systolic BP < 90 mm Hg at Screen A visit after a period of rest;
11. History of malignancy within 5 years prior to Screen A visit, with the exception of localized skin or cervical carcinomas;
12. Systemic immunosuppression for more than 2 weeks, cumulatively, within the 12 weeks prior to randomization or anticipated need for immunosuppression during the study.
13. Untreated or uncontrolled active bacterial, fungal, or viral infection;
14. Participation in other investigational clinical studies within 30 days prior to Day 1;
15. Unwilling to practice acceptable methods of birth control (both males who have partners of childbearing 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;
16. Women who are pregnant or breastfeeding;
17. Known hypersensitivity to any component of the study drug;
18. Any abnormal laboratory level that, in the opinion of the investigator, would put the patient at risk by trial enrollment;
19. Patient is, in the opinion of the investigator, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified