A Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients With Rare Chronic Kidney Diseases – PHOENIX

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Brief Title

A Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients With Rare Chronic Kidney Diseases - PHOENIX

Official Title

A Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients With Rare Chronic Kidney Diseases

Brief 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.
    


Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Increase in eGFR from baseline

Secondary Outcome

 Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Condition

IgA Nephropathy

Intervention

Bardoxolone methyl capsules

Study Arms / Comparison Groups

 Patients with baseline ACR > 300 mg/g but ≤ 2,500 mg/g
Description:  Patients will receive bardoxolone methyl throughout the study. Patients with baseline ACR > 300 mg/g will be titrated to a maximum dose of 30 mg of bardoxolone methyl. They will start with once-daily dosing at 5 mg and will dose-escalate to 10 mg at Week 2, 20 mg at week 4, and then to 30 mg at Week 6.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

103

Start Date

December 26, 2017

Completion Date

January 29, 2019

Primary Completion Date

January 2, 2019

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.
      

Gender

All

Ages

18 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03366337

Organization ID

402-C-1702


Responsible Party

Sponsor

Study Sponsor

Reata Pharmaceuticals, Inc.


Study Sponsor

, , 


Verification Date

December 2019