A Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients With Rare Chronic Kidney Diseases
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 103
- 试验地点
- 29
- 主要终点
- Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12
研究概览
简要总结
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.
详细描述
Study Sponsor, originally Reata Pharmaceuticals, Inc., is now Reata Pharmaceuticals, Inc., a wholly owned subsidiary of Biogen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 m
- •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.
排除标准
- •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.
研究组 & 干预措施
Bardoxolone Methyl - ADPKD
Participants with autosomal polycystic kidney disease (ADPKD) will receive bardoxolone methyl capsules at a starting dose of 5 mg and titrate up to a maximal dose of 20 mg (participants with UACR less than or equal to 300 mg/g) or 30 mg (participants with UACR greater than 300 mg/g) daily.
干预措施: Bardoxolone methyl capsules (Drug)
Bardoxolone Methyl - IgAN
Participants with IgA nephropathy (IgAN) will receive bardoxolone methyl capsules at a starting dose of 5 mg and titrate up to a maximal dose of 20 mg (participants with UACR less than or equal to 300 mg/g) or 30 mg (participants with UACR greater than 300 mg/g) daily.
干预措施: Bardoxolone methyl capsules (Drug)
Bardoxolone Methyl - T1D
Participants with Type 1 diabetes (T1D) will receive bardoxolone methyl capsules at a starting dose of 5 mg and titrate up to a maximal dose of 20 mg (participants with UACR less than or equal to 300 mg/g) or 30 mg (participants with UACR greater than 300 mg/g) daily.
干预措施: Bardoxolone methyl capsules (Drug)
Bardoxolone Methyl - FSGS
Participants with focal segmental glomerulosclerosis (FSGS) will receive bardoxolone methyl capsules at a starting dose of 5 mg and titrate up to a maximal dose of 20 mg (participants with UACR less than or equal to 300 mg/g) or 30 mg (participants with UACR greater than 300 mg/g) daily.
干预措施: Bardoxolone methyl capsules (Drug)
结局指标
主要结局
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 12
时间窗: 12 weeks after participant receives the first dose
To assess the change in eGFR from baseline to week 12. eGFR is a measure of kidney function assessed through blood/serum. Higher eGFRs represent better/improved kidney function. Lower eGFRs represent poorer/decreased kidney function.
次要结局
未报告次要终点