A Phase 3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Autosomal Dominant Polycystic Kidney Disease
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Biogen
- 入组人数
- 667
- 试验地点
- 134
- 主要终点
- Off-treatment Period: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 108
研究概览
简要总结
This international, multi-center, randomized, double-blind, placebo-controlled Phase 3 trial will study the safety, tolerability, and efficacy of bardoxolone methyl in qualified patients with ADPKD. Approximately 850 patients will be enrolled.
详细描述
This international, multi-center, randomized, double-blind, placebo-controlled Phase 3 trial will study the safety, tolerability, and efficacy of bardoxolone methyl in qualified patients with ADPKD.
Patients will be randomized 1:1 to either bardoxolone methyl or placebo. Patients receiving bardoxolone methyl will start with once-daily dosing at 5 mg and will dose-escalate to 10 mg at Week 2, to 20 mg at Week 4, and then to 30 mg at Week 6 (only if baseline ACR >300 mg/g) unless contraindicated clinically and approved by the medical monitor. Dose de-escalation is permitted during the study if indicated clinically, and subsequent dose re-escalation is also permitted to meet the dosing objective of the highest tolerated dose.
All patients in the study will follow the same visit and assessment schedule. Patients will continue to receive study drug or placebo through Week 100 and will not receive study drug or placebo during a 12-week off-treatment period between Weeks 100 and 112.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 12 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients 12 ≤ age ≤ 70 upon study consent;
- •Diagnosis of ADPKD by modified Pei-Ravine criteria (for adults 18≤ age ≤70 years): 1) at least 3 cysts per kidney by sonography or at least 5 cysts by CT or MRI with family history of ADPKD or 2) at least 10 cysts per kidney by any radiologic method and exclusion of other cystic kidney diseases if without family history;
- •Screening eGFR (average of Screen A and Screen B eGFR values) ≥ 30 to≤ 90 mL/min/1.73 m2 (12 to 55 years) or ≥ 30 to ≤ 44 mL/min/1.73 m2 (56 to 70 years):
- •Patients with either screening eGFR ≥ 60 to ≤ 90 mL/min/1.73 m2 or age 56 to 70 years, must have evidence of ADPKD progression (i.e., eGFR decline of ≥ 2.0 mL/min/1.73 m2 per year, based on historical eGFR data and medical monitor discretion); 2)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;
- •Systolic blood pressure ≤ 140 mmHg and diastolic blood pressure ≤ 90 mmHg at Screen A or B visit after a period of rest.
排除标准
- •History of administration of polycystic kidney disease-modifying agents (somatostatin analogues) within 2 months prior to the Screen A visit;
- •B-type natriuretic peptide (BNP) level > 200 pg/mL at Screen A visit;
- •Uncontrolled diabetes (HbA1c > 11.0%) at Screen A visit;
- •Serum albumin < 3 g/dL at Screen A visit;
- •History of intracranial aneurysms;
- •Kidney or any other solid organ transplant recipient or a planned transplant during the study;
- •Acute dialysis or acute kidney injury within 12 weeks prior to Screen A visit or during Screening;
- •History of clinically significant left-sided heart disease and/or clinically significant cardiac disease;
- •Systolic BP < 90 mm Hg at Screen A visit after a period of rest;
- •BMI < 18.5 kg/m2 at the Screen A visit;
- •History of malignancy within 5 years prior to Screen A visit, with the exception of localized skin or cervical carcinomas;
- •Systemic immunosuppression for more than 2 weeks, cumulatively, within the 12 weeks prior to randomization or anticipated need for immunosuppression during the study;
- •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;
- •Concomitant use of tolvaptan is excluded. Patients previously treated with tolvaptan must have discontinued drug for at least 2 months prior to Screen A visit
研究组 & 干预措施
Maximum bardoxolone methyl dose of 20 mg
Patients randomized to receive bardoxolone methyl with a baseline ACR less than or equal to 300 mg/g will be titrated to a maximum dose of 20 mg. Patients will begin once-daily dosing with bardoxolone methyl capsules at 5 mg and will dose escalate to 10 mg at Week 2 and 20 mg at Week 4.
Patients will continue to receive study drug through Week 100, and will not receive study drug during a 12-week off-treatment period between Weeks 100 and 112.
干预措施: Bardoxolone methyl oral capsule (Drug)
Maximum bardoxolone methyl dose 30 mg
Patients randomized to receive bardoxolone methyl with a baseline ACR greater than 300 mg/g will be titrated to a maximum dose of 30 mg. Patients will begin once-daily dosing with bardoxolone methyl capsules at 5 mg and will dose escalate to 10 mg at Week 2, 20 mg at Week 4 and 30 mg at Week 6.
Patients will continue to receive study drug through Week 100, and will not receive study drug during a 12-week off-treatment period between Weeks 100 and 112.
干预措施: Bardoxolone methyl oral capsule (Drug)
Placebo
Patients randomized to placebo will remain on placebo capsules throughout the study, undergoing sham titration.
Patients will continue to receive placebo capsules through Week 100, and will not receive capsules during a 12-week off-treatment period between Weeks 100 and 112.
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Off-treatment Period: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 108
时间窗: Baseline, Week 108
Estimated Glomerular filtration rate (eGFR) is a measure of kidney function assessed through blood/serum. eGFR was measured in milliliters per minute per 1.73 meters square (mL/min/1.73 m\^2). Higher eGFRs represent better/improved kidney function. Lower eGFRs represent poorer/decreased kidney function. Negative change from baseline in eGFR indicates worsened kidney function.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
时间窗: From first dose of the study drug up to end of follow-up (up to Week 112)
AE:any untoward medical occurrence in a participant regardless of its causal relationship to study drug.AE can be any unfavorable \& unintended sign,symptom/disease temporally associated with use of study drug,whether considered to be study-drug related/not.This includes clinically significant abnormal laboratory test result,any newly occurring events/previous conditions that have increased in severity/frequency since administration of study drug. SAE:any AE that at any dose results in death,life-threatening,requires hospitalization/prolongation of existing hospitalisation,substantial disruption of ability to conduct normal life functions,congenital anomaly or is an important medical event. AEs \& SAEs that occurred during treatment and within 30 days after last dose were considered TE.
次要结局
- Treatment Period: Change From Baseline in eGFR at Week 100(Baseline, Week 100)