A Phase 1/2, Single-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Safety, Tolerability, Pharmacokinetic and Pharmacodynamics Study of Subcutaneously Administered ALN-GO1 in Healthy Adult Subjects, and Patients With Primary Hyperoxaluria Type 1
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Number of Participants With Adverse Events (AEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single-ascending doses (SAD) and multiple-ascending doses (MAD) of lumasiran in healthy adult volunteers and subjects with primary hyperoxaluria type 1 (PH1). In Part A, single ascending dose (SAD) part, healthy adults were dosed with lumasiran or placebo once. In Part B, multiple ascending doses (MAD) part, patients with primary hyperoxaluria type 1 (PH1) were dosed with lumasiran or placebo. All patients that initially received placebo received lumasiran after completing placebo dosing.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 6 Years 至 64 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Part A: SAD: Placebo
A single dose of matching placebo will be administered subcutaneously (SC).
干预措施: Placebo (Drug)
Part A: SAD: Lumasiran 0.3 mg/kg
A single dose of 0.3 mg/kg lumasiran will be administered SC.
干预措施: Lumasiran (Drug)
Part A: SAD: Lumasiran 1.0 mg/kg
A single dose of 1.0 mg/kg lumasiran will be administered SC.
干预措施: Lumasiran (Drug)
Part A: SAD: Lumasiran 3.0 mg/kg
A single dose of 3.0 mg/kg lumasiran will be administered SC.
干预措施: Lumasiran (Drug)
Part A: SAD: Lumasiran 6.0 mg/kg
A single dose of 6.0 mg/kg lumasiran will be administered SC.
干预措施: Lumasiran (Drug)
Part B: MAD: Placebo
Participants with primary hyperoxaluria type 1 (PH1) will be treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo treated participants will cross over to their respective Part B lumasiran arms in the Part B: MAD Study Day 85-End of Study Period and will then be treated with lumasiran. The estimated total time on study was up to 546 days.
干预措施: Placebo (Drug)
Part B: MAD: Lumasiran 1.0 mg/kg qM
Participants with PH1 will be treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85.
干预措施: Lumasiran (Drug)
Part B: MAD: Lumasiran 3.0 mg/kg qM
Participants with PH1 will be treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85.
干预措施: Lumasiran (Drug)
Part B: MAD: Lumasiran 3.0 mg/kg q3M
Participants with PH1 will be treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study is up to 546 days. One participant from the Part B: MAD: Placebo arm will cross over to this lumasiran arm at Day 85. For this participant treatment with lumasiran starts at Day 85.
干预措施: Lumasiran (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs)
时间窗: Part A (SAD): Up to 405 days; Part B (MAD): Up to 546 days
An AE is any untoward medical occurrence in a clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
次要结局
- Maximum Concentration (Cmax) of Lumasiran in Plasma(Part A (SAD): Day 1: predose, 30 minutes (min), 1 hour (h), 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h)
- Time to Cmax (Tmax) of Lumasiran in Plasma(Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h)
- Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of Lumasiran in Plasma(Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h)
- Terminal Half-life (t1/2) of Lumasiran in Plasma(Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h)
- Fraction Excreted in Urine in 24 Hours (Fe0-24) of Lumasiran(Part A (SAD): Day 1: pooled urine 0-4 h, 4-8 h and 8-24 h; Part B (MAD): Part B (MAD phase): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: pooled urine 0-4 h, 4-8 h, 8-12 h and 12-24 h)
- Renal Clearance (CLR) of Lumasiran(Part A (SAD): Day 1: pooled urine 0-4 h, 4-8 h and 8-24 h; Part B (MAD): Part B (MAD phase): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: pooled urine 0-4 h, 4-8 h, 8-12 h and 12-24 h)
- Baseline Plasma Glycolate Concentration(Part A (SAD): Baseline, Part B (MAD): Baseline)
- Percentage Change From Baseline in Plasma Glycolate Concentration(Part A (SAD): Days 15, 29, 57 and 85; Part B (MAD): Days 15, 29, 57, 85)
- Baseline Spot Urine Glycolate:Creatinine Ratio in Part A(Part A (SAD): Baseline)
- Percentage Change From Baseline in Spot Urine Glycolate:Creatinine Ratio in Part A(Part A (SAD): Days 29 and 57)
- Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B(Part B (MAD): Baseline)
- Percentage Change From Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B(Part B (MAD): 24 hour urine collections on Days 29, 57, 85, 113, 141, 169, 197)
- Baseline 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days(Part B (MAD): Baseline)
- Percentage Change From Baseline of 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days(Part B (MAD): 24 hour urine collections on Days 29, 57 and 85)
- Baseline Creatinine Clearance Corrected for BSA in Part B(Part B (MAD): Baseline)
- Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B(Part B (MAD): Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449)