Clinical trial NCT03366337: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: IgA Nephropathy
CKD Associated With Type 1 Diabetes
Focal Segmental Glomerulosclerosis
Autosomal Dominant Polycystic Kidney
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
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2017-12-08
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12
timeFrame: 12 weeks after participant receives the first dose
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Phoenician Centers for Research & Innovation (PCRI)
state: Arizona
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Denver
country: United States
facility: Denver Nephrology
state: Colorado
city: Clearwater
country: United States
facility: Gulfcoast Endocrine and Diabetes Center
state: Florida
city: Lauderdale Lakes
country: United States
facility: South Florida Research Institute
state: Florida
city: Port Charlotte
country: United States
facility: Coastal Nephrology Associates
state: Florida
city: Augusta
country: United States
facility: Kidney Care Augusta
state: Georgia
city: Caldwell
country: United States
facility: Boise Kidney & Hypertension, PLLC
state: Idaho
city: Meridian
country: United States
facility: Boise Kidney & Hypertension, PLLC
state: Idaho
city: Evergreen Park
country: United States
facility: Research By Design
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Paducah
country: United States
facility: Four Rivers Clinical Research, Inc
state: Kentucky
city: Shreveport
country: United States
facility: Northwest Louisiana Nephrology
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center - Division of Nephrology Tufts Medical Center
state: Massachusetts
city: Kansas City
country: United States
facility: Clinical Research Consultants, LLC
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center - Nephrology
state: New York
city: Greenville
country: United States
facility: Physician's East Endocrine Research
state: North Carolina
city: Columbus
country: United States
facility: Remington-Davis Clinical Research
state: Ohio
city: Bethlehem
country: United States
facility: Northeast Clinical Research Center, LLC
state: Pennsylvania
city: Providence
country: United States
facility: The Warren Alpert School of Brown University
state: Rhode Island
city: Chattanooga
country: United States
facility: Nephrology Associates
state: Tennessee
city: Austin
country: United States
facility: Research Management, Inc.
state: Texas
city: Dallas
country: United States
facility: Renal Disease Research Intitute
state: Texas
city: San Antonio
country: United States
facility: Renal Associates, PA
state: Texas
city: West Jordan
country: United States
facility: Advanced Clinical Research
state: Utah
city: Fairfax Station
country: United States
facility: Mendez Center for Clinical Research LLC
state: Virginia
city: Federal Way
country: United States
facility: Larry Stonesifer, M.D.
state: Washington
Study officials:
References: