A Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients With Rare Chronic Kidney Diseases - PHOENIX
Condition: IgA Nephropathy; CKD Associated With Type 1 Diabetes; Focal Segmental Glomerulosclerosis; Autosomal Dominant Polycystic Kidney
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Polycystic Kidney Diseases; Glomerulonephritis, IGA; Polycystic Kidney, Autosomal Dominant; Glomerulosclerosis, Focal Segmental; Diabetes Mellitus, Type 1
Intervention: Bardoxolone methyl capsules
Intervention description: Bardoxolone 5 mg capsules
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 103.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: IgA Nephropathy; CKD associated with type 1 diabetes; Focal segmental glomerulosclerosis; Autosomal dominant polycystic kidney disease; IgAN; FSGS; ADPKD; Bardoxolone methyl; CDDO-ME; RTA 402

Summary:

      This multi-center, open-label Phase 2 trial will study the safety, tolerability, and efficacy
      of bardoxolone methyl in qualified patients with the following rare chronic kidney diseases
      (CKD): CKD associated with type 1 diabetes (T1D), IgA nephropathy (IgAN), focal segmental
      glomerulosclerosis (FSGS), and autosomal dominant polycystic kidney disease (ADPKD). Patients
      will be enrolled in disease specific cohorts within the trial, and effectiveness of
      bardoxolone methyl in treating CKD will be assessed separately by cohort for each rare CKD.

      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, and 12, and by telephone contact on Days 3, 10, 21, 31, 38, and 45. Patients
      will also be scheduled to be assessed at an in-person follow-up visit at Week 16, four weeks
      after the end of treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female patients 18 ≤ age ≤ 65 upon study consent;

          -  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%;

          -  Albumin to creatinine ratio (ACR) ≤ 2500 mg/g at Screen B visit;

          -  If receiving an angiotensin-converting enzyme (ACE) inhibitor and/or an angiotensin II
             receptor blocker (ARB), patients should be prescribed the maximally tolerated labeled
             daily dose (MTLDD) for at least 6 weeks prior to the Screen A visit;

          -  For patients enrolling in T1D Cohort: Diagnosis of type 1 diabetes confirmed by
             fasting C-peptide level. Diagnosis must have been made ≤ 35 years of age; and
             prescribed stable dose of insulin to maintain adequate glucose control for at least 6
             months prior to the Screen A visit;

          -  For patients enrolling in IgAN Cohort: Biopsy-confirmed IgA nephropathy;

          -  For patients enrolling in FSGS Cohort: Biopsy-confirmed FSGS that is not due to known
             secondary causes including morbid obesity, decreased renal mass, viral infections,
             drug-induced nephrotoxicity, or prior history of vasculitis;

          -  For patients enrolling in ADPKD Cohort: Genetic confirmation of PKD1 mutation;

          -  Adequate bone marrow reserve and organ function at the Screen A visit as follows:
             Hematologic: Absolute neutrophil count > 1.5 x 109/L, platelets > 100 x 109/L,
             hemoglobin (Hgb) ≥ 9 g/dL; and Hepatic: Total bilirubin (TBL) ≤ 1.5 times the upper
             limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase
             (AST) ≤ 1.5 times ULN.

        Exclusion Criteria:

          -  Kidney or any other solid organ transplant recipient or a planned transplant during
             the study;

          -  B-type natriuretic peptide (BNP) level > 200 pg/mL at Screen A visit;

          -  Acute dialysis or acute kidney injury within 12 weeks prior to Screen A visit or
             during Screening;

          -  Serum albumin < 3 g/dL at Screen A visit;

          -  Systemic immunosuppression for more than 2 weeks, cumulatively, within the 12 weeks
             prior to randomization or anticipated need for immunosuppression during the study;

          -  For patients enrolling in IgAN Cohort: Systemic manifestations of Henoch-Schonlein
             purpura within 1 year prior to Screen A visit; or have used belimumab, eculizumab, or
             rituximab within 6 months prior to Screen A visit;

          -  For patients enrolling in ADPKD Cohort: Receiving tolvaptan;

          -  Cerebrovascular event (stroke, transient ischemic attack) or aneurysm within 6 months
             prior to Screen A visit or during Screening;

          -  History of clinically significant left-sided heart disease and/or clinically
             significant cardiac disease;

          -  Uncontrolled systemic hypertension;

          -  Systolic BP < 90 mm Hg at Screen A visit after a period of rest;

          -  History of malignancy within 2 years prior to Screen A visit, with the exception of
             localized skin or cervical carcinomas;

          -  Uncontrolled diabetes (HbA1c > 10.0%) at Screen A visit;

          -  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.