ILLUMINATE-A: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study With an Extended Dosing Period to Evaluate the Efficacy and Safety of Lumasiran in Children and Adults With Primary Hyperoxaluria Type 1
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of lumasiran in children and adults with primary hyperoxaluria type 1 (PH1).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing to provide written informed consent or assent and to comply with study requirements
- •Confirmation of PH1 disease
- •Meet the 24 hour urine oxalate excretion requirements
- •If taking Vitamin B6 (pyridoxine), must have been on stable regimen for at least 90 days
排除标准
- •Clinically significant health concerns (with the exception of PH1) or clinical evidence of extrarenal systemic oxalosis
- •Clinically significant abnormal laboratory results
- •Known active or evidence of HIV or hepatitis B or C infection
- •An estimated GFR of < 30 mL/min/1.73m^2 at screening
- •Received an investigational agent within 30 days or 5 half-lives before the first dose of study drug or are in follow-up of another clinical study
- •History of kidney or liver transplant
- •Known history of multiple drug allergies or allergic reaction to an oligonucleotide or GalNAc
- •History of intolerance to subcutaneous injection
- •Women who are pregnant, planning a pregnancy, or breast-feeding or those of child bearing potential and not willing to use contraception
- •History of alcohol abuse within the last 12 months, or unable or unwilling to limit alcohol consumption throughout the study
研究组 & 干预措施
Placebo/Lumasiran
Lumasiran-matching placebo (normal saline [0.9% NaCl]) was administered subcutaneously (SC) at Day 1 and Months 1, 2 and 3 during the 6-Month Double-blind (DB) Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month Open-label Extension (OLE) period.
干预措施: Placebo (Drug)
Placebo/Lumasiran
Lumasiran-matching placebo (normal saline [0.9% NaCl]) was administered subcutaneously (SC) at Day 1 and Months 1, 2 and 3 during the 6-Month Double-blind (DB) Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month Open-label Extension (OLE) period.
干预措施: Lumasiran (Drug)
Lumasiran/Lumasiran
Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
干预措施: Placebo (Drug)
Lumasiran/Lumasiran
Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
干预措施: Lumasiran (Drug)
结局指标
主要结局
Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6
时间窗: Baseline to Month 6
Percent change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average percent change from baseline across Months 3 through 6. Only valid urine samples without any non-protocol-related issues were included in the analysis. A negative change from Baseline indicates a favorable outcome.
次要结局
- Percent Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline to Month 6(Baseline to Month 6)
- Percentage Change in Plasma Oxalate From Baseline to Month 6(Baseline to Month 6)
- Percentage Change in 24-hour Urinary Oxalate Excretion Corrected by BSA From Baseline in the Extension Period(From Baseline to Month 54 and Month 60)
- Absolute Change in 24-hour Urinary Oxalate Corrected for BSA From Baseline to Month 6(Baseline to Month 6)
- Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below 1.5 x ULN at Month 6(Month 6)
- Percentage of Participants With 24-hour Urinary Oxalate Level Corrected for BSA at or Below ULN at Month 6(Month 6)
- Absolute Change in Plasma Oxalate From Baseline to Month 6(Baseline to Month 6)
- Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Week 2 and Months 1, 2, 3, 4, 5 and 6(Baseline, Week 2, Months 1, 2, 3, 4, 5 and 6)
- Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for BSA From Baseline in the Extension Period(From Baseline to Month 54 and Month 60)
- Percentage of Time That 24-hour Urinary Oxalate is at or Below 1.5 × ULN During Lumasiran Treatment(Up to Month 60)
- Absolute Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline in the Extension Period(From Baseline to Month 54 and Month 60)
- Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline in the Extension Period(From Baseline to Month 54 and Month 60)
- Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60).)