A Phase 3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients with Polycystic Kidney Disease
- Conditions
- Autosomal dominant polycystic kidney diseaseMedDRA version: 20.0Level: LLTClassification code 10036046Term: Polycystic kidney, autosomal dominantSystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2018-004651-20-PL
- Lead Sponsor
- Reata Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 850
1. Male and female patients 12 = age = 70 upon study consent;
2. Diagnosis of ADPKD
a. For adult (18 = age = 70 years) diagnosis of ADPKD by modified Pei-Ravine criteria:
i. at least 3 cysts per kidney by sonography or at least 5 cysts by CT or MRI with family history of ADPKD or
ii. at least 10 cysts per kidney by any radiologic method and exclusion of other cystic kidney diseases if without family history;
b. For adolescent (12 = age < 18 years) diagnosis of ADPKD by:
i. the presence of family history and/or genetic diagnosis and the presence of at least 1 cyst of 0.5 cm on ultrasound or MRI,
ii. patients without a family history or genetic diagnosis must have at least 10 bilateral renal cysts in total, and exclusion of other cystic kidney diseases;
3. eGFR must:
a. Have a percent difference = 25% at screening (the values at Screen A and Screen B), and;
b. Have an average (the values at Screen A and Screen B) = 30 to = 90 mL/min/1.73 m^2 for patients 12 to 55 years or = 30 to = 44 mL/min/1.73 m^2 for patients 56 to 70 years, and;
c. Support ADPKD disease progression (i.e., average yearly eGFR decline of = 2.0 mL/min/1.73 m^2 for the past two years) for patients with either screening eGFR = 60 to = 90 mL/min/1.73 m^2 or age 56 to 70 years
4. ACR = 2500 mg/g at Screen B visit;
5. Systolic blood pressure = 140 mmHg and diastolic blood pressure = 90 mmHg at Screen A or Screen B visit after a period of rest. Patients receiving an angiotensin-converting enzyme (ACE) inhibitor and/or an angiotensin II receptor blocker (T2T) must be on a stable dose for at least 6 weeks prior to the Screen A visit;
6. Adequate bone marrow reserve and organ function at the Screen A visit as follows:
a. Hematologic: Absolute neutrophil count > 1.5 x 10^9/L, platelets > 100 x 10^9/L, hemoglobin (Hgb) = 9 g/dL;
b. Hepatic: Total bilirubin (TBL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) = the upper limit of normal (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/assent document indicating that the patient has been informed of all pertinent aspects of the study prior to initiation of any protocol-mandated procedures.
10. Patients receiving an SGLT2 inhibitor must be on a stable dose for at least 4 weeks prior to the Screen A visit.
Are the trial subjects under 18? yes
Number of subjects for this age range: 40
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 750
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60
1. Prior exposure to bardoxolone methyl;
2. Use of tolvaptan within 2 months prior to Screen A. Initiation of concomitant tolvaptan use during the study is not permitted;
3. History of administration of polycystic kidney disease-modifying agents (somatostatin analogues) within 2 months prior to the Screen A visit;
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. Serum albumin < 3 g/dL at Screen A visit;
7. History of intracranial aneurysms;
8. Kidney or any other solid organ transplant recipient or a planned transplant during the study;
9. Acute dialysis or acute kidney injury within 12 weeks prior to Screen A visit or during Screening;
10. 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 III or IV;
h. History of untreated atrial fibrillation;
i. History of unstable arrhythmias;
11. Systolic BP < 90 mm Hg at Screen A visit after a period of rest;
12. BMI < 18.5 kg/m^2 at the Screen A visit;
13. History of malignancy within 5 years prior to Screen A visit, with the exception of localized skin or cervical carcinomas;
14. Systemic immunosuppression for more than 2 weeks, cumulatively, within the 12 weeks prior to randomization or anticipated need for immunosuppression during the study;
15. Untreated or uncontrolled active bacterial, fungal, or viral infection;
16. Participation in other interventional clinical studies within 30 days prior to Day 1;
17. 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;
18. Women who are pregnant or breastfeeding;
19. Known hypersensitivity to any component of the study drug;
20. Any abnormal laboratory level that, in the opinion of the investigator, would put the patient at risk by trial enrollment;
21. 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;
22. Coronavirus disease 2019 (COVID-19) pneumonia, related acute kidney injury, or related hospitalization within 6 months prior to Day 1.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method