A Double-Blind, Randomized, Placebo-Controlled Safety Study Evaluating the Effects of Residual Renal Function (RFF) in Patients With End-Stage Renal Disease and Type 2 Diabetes Mellitus on Peritoneal Dialysis

Study Overview
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Brief Summary
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This study is a multi-center, double-blinded, randomized, study of bardoxolone methyl treatment in patients with End-Stage Renal Disease (ERSD) and Type 2 Diabetes Mellitus (T2DM) on peritoneal dialysis.

Detailed Description
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This study was previously posted by Reata Pharmaceuticals. In September 2023, sponsorship of the trial was transferred to Biogen.

Conditions
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End-Stage Renal Disease, Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Bardoxolone Methyl 20 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have ESRD and been on PD for longer than 3 months Patients must have had a diagnosis of T2DM prior to starting dialysis Patients must have RRF, as defined by the mean of urea and creatinine clearance on a 24 hour urine collection, ≥ 25 Liters/week/1.73 m2 documented in the four months prior to the Screen A visit Patients must have RRF, as defined by the mean of urea and creatinine clearances on a 24 hour urine collection, ≥ 25 Liters/week/1.73 m2 at both the Screen A and Screen B visits The RRF value obtained at the Screen B visit, must not be less than 50% of the RRF value obtained at the Screen A visit Patients must be at least 18 years of age Patients must have a mean systolic blood pressure (SBP) on three readings at both Screen A and Screen B visits ≤ 160 mmHg and ≥ 90 mmHg Patients must have a mean diastolic blood pressure (DBP) on three readings at both Screen A and Screen B visits < 100 mmHg and ≥ 40 mmHg Patients must be willing to practice 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 Patients must be willing and able to cooperate with all aspects of the protocol Patients must be willing and able to give written informed consent to participate in the study. They must provide consent for access to medical data according to appropriate local data protection legislation and allow authorization to access medical records that describe events captured in the endpoints Exclusion Criteria: History of Autosomal Dominant Polycystic Kidney Disease Currently Active Systemic Lupus Erythematosus History of Hepatitis B Surface Antigen + History of Hepatitis C Antibody + being treated with antiviral therapy History of an organ transplant A planned renal transplant from a living donor during the study History of hospitalization for congestive heart failure or pulmonary edema within 12 weeks before study randomization History of cirrhosis of the liver History of amyloidosis or light chain nephropathy History of hemoglobin A1c level > 11.0% (97 mmol/mol) within 12 weeks before study randomization History of recently active cardiovascular disease defined as: Unstable angina pectoris within 12 weeks before study randomization Myocardial infarction, coronary artery bypass graft surgery, or percutaneous transluminal coronary angioplasty/stent within 12 weeks before study randomization Cerebrovascular accident, including transient ischemic attack within 12 weeks before study randomization History of a diagnostic or interventional procedure that required intravenous administration of an iodinated contrast agent or gadolinium within 12 weeks before study randomization History of known severe obstructive valvular heart disease or severe obstructive hypertrophic cardiomyopathy History of known 2o or 3o atrioventricular block not successfully treated with a pacemaker History or resuscitated sudden cardiac death History of an automatic implantable defibrillator QTc greater than 0.50 seconds on an ECG obtained during either Screen A or Screen B visits A serum magnesium level less than 1.4 meq/L on either Screen A or Screen B visit laboratory test results History of systemic immunosuppression for more than 15 days, cumulatively, within the 12 weeks prior to study randomization or anticipated need for more than 15 days of immunosuppression during the study Total bilirubin, aspartate transaminase (AST), or alanine transaminase (ALT) level greater than the upper limit of normal (ULN) or alkaline phosphatase level greater than two times the ULN on either the Screen A and Screen B visit laboratory test results Known hypersensitivity to any component of the study drug Current history of drug or alcohol abuse, as assessed by the investigator History of clinically significant infection requiring intravenous administration of antibiotics or hospitalization within 12 weeks before study randomization In patients who have been on peritoneal dialysis for ≥ 6 months, two or more episodes of peritonitis in the 6 months before study randomization. In patients who have been on peritoneal dialysis for <6 months, one episode of peritonitis before study randomization History of a diagnosis or treatment of a malignancy in the past 5 years, excluding non-melanoma skin cancer and carcinoma in situ of the cervix History of a clinical condition that, in the judgment of the investigator, could potentially pose a health risk to the patient while involved in the study Patient is unable to communicate or cooperate with the investigator due to language problems, poor mental development, or impaired cerebral function Participation in a clinical study involving any intervention within 30 days prior to Screen A visit, concurrent participation in such a study, or participation in a prior clinical study involving bardoxolone methyl in any form Female patients who are pregnant, intend to become pregnant during this study, or are nursing

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Oral, once daily<br>|
| Experimental: Bardoxolone Methyl<br> | Drug: Bardoxolone Methyl 20 mg<br>* Oral, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events |  | Approximately 17 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Type of Adverse Events |  | Approximately 17 months | 
| Change in Residual Renal Function |  | Baseline to 6 months | 
| Maximum observed concentration |  | Day 0, 30, 60, 90, 120, 150, 180, 210 | 
| Time to maximum observed concentration |  | Day 0, 30, 60, 90, 120, 150, 180, 210 | 
| Area under the plasma concentration-time curve | Only the first 8 patients randomized will have the PK drawn and hours 2, 4, 8, and 24. All patients will have the PK drawn at 30, 60, 90, 120, 150 and 180 days. | 2, 4, 8, 24 hours, 30, 60, 90, 120, 150 and 180 days | 
| Area under the curve | Only the first 8 patients randomized | 2, 4, 8 and 24 hours |