MOSAIC - A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study Evaluating the Efficacy and Safety of Selonsertib in Subjects With Moderate to Advanced Diabetic Kidney Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 384
- 试验地点
- 109
- 主要终点
- Treatment-specific Baseline Estimated Glomerular Filtration Rate Based on Creatinine (eGFRcr)
研究概览
简要总结
The primary objective of this study is to evaluate whether selonsertib (SEL) can slow the decline in kidney function in participants with moderate to advanced diabetic kidney disease (DKD).
详细描述
Following the screening period, eligible participants will enroll into a Run-in period of at least 5 weeks and receive placebo to match SEL for at least 1 week and then SEL for at least 4 weeks. After completing Run-in period, eligible participants will be randomized and receive either SEL or placebo to match SEL for at least 48 weeks.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of type 2 diabetes mellitus (T2DM) as per local guidelines.
- •Estimated glomerular filtration rate (eGFR) value calculated by central laboratory utilizing samples collected during screening and prior to enrollment of ≥ 20 mL/min/1.73 m^2 to < 60 mL/min/1.73 m^2 with albuminuria
- •eGFR and urine albumin to creatinine ratio (UACR) must meet criteria a, b, or c
- •a: eGFR (mL/min/1.73 m^2): ≥ 45 to < 60; UACR (mg/g): ≥ 600 to 5000
- •b: eGFR (mL/min/1.73 m^2): ≥ 30 to < 45; UACR (mg/g): ≥ 300 to 5000
- •c: eGFR (mL/min/1.73 m^2): ≥ 20 to < 30; UACR (mg/g): ≥ 150 to 5000
- •Treatment with either an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB)
- •Individuals not receiving an ACEi or ARB may be enrolled if there is documented intolerance to ACEi and ARB
- •Individuals receiving less-than-maximal dose of an ACEi or ARB may be enrolled if there is a documented reason that the maximum labeled dose of ACEi and ARB could not be reached
- •Individuals already receiving sodium-glucose co-transporter-2 (SGLT-2) inhibitors must be on a stable dose for at least 2 weeks prior to enrollment
- •Mean systolic blood pressure (SBP) must be <160 mmHg and mean diastolic blood pressure (DBP) must be <100 mmHg
- •Required baseline laboratory data, analyzed by central laboratory, within 30 days prior to enrollment
排除标准
- •Hemoglobin A1c (HbA1c) > 12.0% within 30 days prior to enrollment
- •Individuals with diagnosis of type 1 diabetes mellitus (T1DM) or maturity onset diabetes of the young (MODY)
- •Body mass index (BMI) > 50 kg/m^2
- •UACR > 5000 mg/g on any measurement during screening
- •End stage kidney disease (ESKD) (i.e., chronic hemodialysis, chronic peritoneal dialysis, or history of kidney transplantation)
- •Anticipated progression to ESKD (need for chronic hemodialysis, chronic peritoneal dialysis or receipt of kidney transplant) within 3 months after enrollment
- •Unstable cardiovascular disease
- •Pregnant or lactating females or planning to become pregnant or breastfeed during the study
- •Concurrent use of either
- •ACEi and ARB or
- •Mineralocorticoid receptor antagonist (MRA) or direct renin inhibitor (DRI) in combination with an ACEi or ARB for at least 2 weeks prior to Enrollment
- •Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, ECG finding, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the individual or impair the assessment of study results
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Selonsertib
Run-in Period (5 Weeks): Participants will receive placebo-to-match SEL for at least one week and then SEL 18 mg for at least 4 weeks.
Randomized Period: Participants will be randomized to receive SEL 18 mg for at least 48 weeks.
干预措施: SEL (Drug)
Selonsertib
Run-in Period (5 Weeks): Participants will receive placebo-to-match SEL for at least one week and then SEL 18 mg for at least 4 weeks.
Randomized Period: Participants will be randomized to receive SEL 18 mg for at least 48 weeks.
干预措施: Placebo (Drug)
Placebo
Run-in Period (5 Weeks): Participants will receive placebo-to-match SEL for at least one week and then SEL 18 mg for at least 4 weeks.
Randomized Period: Participants will be randomized to receive placebo-to-match SEL for at least 48 weeks.
干预措施: SEL (Drug)
Placebo
Run-in Period (5 Weeks): Participants will receive placebo-to-match SEL for at least one week and then SEL 18 mg for at least 4 weeks.
Randomized Period: Participants will be randomized to receive placebo-to-match SEL for at least 48 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Treatment-specific Baseline Estimated Glomerular Filtration Rate Based on Creatinine (eGFRcr)
时间窗: Treatment-specific Baselines (From enrollment (Visit A) up to 14 days after Visit A for placebo and from Visit C up to 14 days after Visit C for SEL)
The values of eGFRcr were calculated using the Chronic Kidney Disease Epidemiology (CKD-EPI) Creatinine Equation (2009). eGFRcr = 141\*min(Standardized Serum Creatinine (Scr)/kappa, 1) \^alpha\*max(Scr/ kappa, 1)\^(-1.209)\*0.993\^Age\*1.018\[if female\]\*1.159\[if Black\], where kappa=0.7(females) or 0.9(males), alpha=-0.329(females) or -0.411(males). min indicates the minimum of Scr/kappa or 1, max indicates the maximum of Scr/kappa or 1, and age is in years. Treatment-specific Baselines = the average of Visits A and B values for Placebo, and the average of Visit C and Day 1 values for SEL. Visit A= enrollment, Visit B= 7-14 days after Visit A, Visit C= 21-28 days after Visit B, and Visit 1= 7-14 days after Visit C.
eGFRcr Slope
时间窗: Treatment-specific Baselines through Week 84
The values of eGFRcr were calculated using the CKD-EPI Creatinine Equation (2009). eGFRcr = 141\*min(Scr/kappa, 1) \^alpha\*max(Scr/kappa, 1)\^(-1.209)\*0.993\^Age\*1.018\[if female\]\*1.159\[if Black\], where kappa=0.7(females) or 0.9(males), alpha=-0.329(females) or -0.411(males). min indicates the minimum of Scr/kappa or 1, max indicates the maximum of Scr/kappa or 1, and age is in years. Treatment specific baselines for eGFRcr: average of Visit A (enrollment) and Visit B (7-14 days after Visit A) values for Placebo, and average of Visit C (21-28 days after Visit B, and Visit 1 (7-14 days after Visit C) values for SEL.
次要结局
- Time From Randomization to First Occurrence of a Kidney Clinical Event: Event Rate Per 100 Participant-years for First Occurrence of Kidney Clinical Event(From randomization up to Week 101)
- Pre-run-in Baseline Estimated Glomerular Filtration Rate Based on Cystatin C (eGFRcys)(Pre-run-in Baseline (Pre-run in Baseline = Average of visit A (Enrollment) and Visit B (7-14 days after Visit A) eGFRcys values))
- eGFRcys Slope(Pre-run-in Baseline through Week 84)
- Percentage of Participants With Kidney Clinical Events at Week 48(Week 48)