A Phase 1b, Double-Blind, Placebo-Controlled, Multiple Ascending Dose and an Open-Label Fixed-Dose Study in Patients With Autosomal Dominant Polycystic Kidney Disease to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of RGLS8429
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 68
- 试验地点
- 20
- 主要终点
- Impact of RGLS8429 on ADPKD biomarkers
研究概览
简要总结
Primary Objectives
- To assess the safety and tolerability of RGLS8429
- To assess the impact of RGLS8429 on ADPKD biomarkers
Secondary Objectives
- To assess the impact of RGLS8429 on height-adjusted total kidney volume (htTKV)
- To characterize the pharmacokinetic (PK) properties of RGLS8429
- To assess the impact of RGLS8429 on renal function
详细描述
This is a randomized, double-blind, placebo-controlled multiple ascending dose and an open-label fixed-dose Phase 1b study consisting of two parts, Part A and Part B. In Part A, multiple ascending doses of RGLS8429 or placebo will be administered via subcutaneous injection to subjects with ADPKD to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of RGLS8429. In Part B, a fixed-dose of RGLS8429 will be administered via subcutaneous injection to subjects with ADPKD to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of RGLS8429.
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)
盲法说明
This study will have two parts. Part A is the double-blind, randomized, placebo-controlled study. Part B is the open-label fixed-dose study.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ADPKD patients, 18 to 70 years old
- •Class 1C, 1D, or 1E Mayo Imaging Classification of ADPKD (based upon either the MRI obtained during screening, or a prior MRI obtained within 5 years of screening with documented Mayo classification)
- •eGFR between 30 to 90 mL/min/1.73 m2
- •Body mass index (BMI) 18 to 35 kg/m2
- •Must understand and consent to the study procedures explained in the ICF and be willing and able to comply with the protocol
排除标准
- •Administration of tolvaptan in the 28 days before randomization
- •Subject is mentally incapacitated or has significant emotional problems
- •Any medical condition or social circumstance that, in the opinion of the Investigator, may make the subject unlikely to complete the study or comply with study procedures and requirements; or may pose a risk to the subject's safety
- •History or presence of alcoholism or drug abuse within the past 2 years prior to screening
- •Only one kidney or kidney transplant recipient
- •Participation in another clinical trial and/or exposure to any investigational drug or approved therapy for investigational use within 28 days or 5 half-lives of the investigational drug's dosing, whichever is longer, prior to dosing. The 28-day or 5-half-life windows will be calculated from the date of the last dosing in the previous study to Day 1 of the current study.
研究组 & 干预措施
RGLS8429
The randomized,double blind part of the study (Part A) will consist of three sequential cohorts of approximately 12 subjects each randomized centrally to receive RGLS8429 or placebo by subcutaneous injection every other week (Q2W) x 7 doses (36 subjects total).
- Cohort 1: first dose level of RGLS8429 or placebo
- Cohort 2: second dose level of RGLS8429 or placebo
- Cohort 3: third dose level of RGLS8429 or placebo
干预措施: RGLS8429 (Drug)
Placebo
The randomized double blind part of the study (Part A) will consist of three sequential cohorts of approximately 12 subjects each randomized centrally to receive RGLS8429 or placebo by subcutaneous injection every other week (Q2W) x 7 doses (36 subjects total).
- Cohort 1: first dose level of RGLS8429 or placebo
- Cohort 2: second dose level of RGLS8429 or placebo
- Cohort 3: third dose level of RGLS8429 or placebo
干预措施: Placebo (Drug)
Open Label Fixed Dose RGLS8429
The open-label fixed dose part of the study (Part B and Cohort 4) will consist of a single cohort of up to 30 subjects each receiving 300 mg RGLS8429.
干预措施: RGLS8429 (Drug)
结局指标
主要结局
Impact of RGLS8429 on ADPKD biomarkers
时间窗: Baseline to Day 113
Change from baseline in PC1, PC2, NGAL, and KIM-1 urine biomarkers
Safety and tolerability of RGLS4829: Incidence of AEs
时间窗: Baseline to Day 113
Incidence of adverse events over time
次要结局
- Impact of RGLS8429 on height-adjusted total kidney volume (htTKV)(Baseline to Day 113)
- Pharmacokinetic properties of RGLS8429: t½(Baseline to Day 113)
- Pharmacokinetic properties of RGLS8429: Cmax(Baseline to Day 113)
- Pharmacokinetic properties of RGLS8429: Tmax(Baseline to Day 113)