A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 1b/2a Study of WVE-120101 Administered Intrathecally in Patients With Huntington's Disease
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 61
- 试验地点
- 21
- 主要终点
- Safety: Severity of Adverse Events
研究概览
简要总结
PRECISION-HD1 is a Phase 1b/2a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses of WVE-120101 in adult patients with early manifest Huntington's disease (HD) who carry a targeted single nucleotide polymorphism (SNP) rs362307 (SNP1).
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
- 25 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Prescreened with targeted SNP on the same allele as the pathogenic CAG expansion
- •Ambulatory, male or female patients aged ≥25 - ≤65 years
- •Clinical diagnostic motor features of HD, defined as Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Score = 4
- •Early manifest HD, Stage I or Stage II based on UHDRS Total Functional Capacity Scores ≥7 and ≤13
排除标准
- •Malignancy or received treatment for malignancy, other than treated basal cell or squamous cell carcinoma of the skin, within the previous 5 years.
- •Received investigational drug or implantable device in prior 3 months or investigational oligonucleotide in prior 6 months or 5 half-lives of the oligonucleotide, whichever is longer
- •Clinically significant medical condition, unstable psychiatric symptoms, substance abuse, or pregnancy
- •Inability to undergo brain MRI
- •Bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture
研究组 & 干预措施
WVE-120101 (Dose D) or placebo
干预措施: Placebo (Drug)
WVE-120101 (Dose E) or placebo
干预措施: WVE-120101 (Drug)
WVE-120101 (Dose A) or placebo
干预措施: WVE-120101 (Drug)
WVE-120101 (Dose A) or placebo
干预措施: Placebo (Drug)
WVE-120101 (Dose B) or placebo
干预措施: WVE-120101 (Drug)
WVE-120101 (Dose B) or placebo
干预措施: Placebo (Drug)
WVE-120101 (Dose C) or placebo
干预措施: WVE-120101 (Drug)
WVE-120101 (Dose C) or placebo
干预措施: Placebo (Drug)
WVE-120101 (Dose D) or placebo
干预措施: WVE-120101 (Drug)
WVE-120101 (Dose E) or placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Safety: Severity of Adverse Events
时间窗: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
Number of patients who experienced a severe treatment-emergent adverse event. Severity was evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Safety: Number of Patients With Serious TEAEs
时间窗: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
A serious TEAE is defined as any event that results in death, is immediately life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect not present at Prescreening.
Safety: Number of Patients With Treatment-emergent Adverse Events (TEAEs)
时间窗: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
All TEAEs reported or observed during the study, including TEAEs resulting from concurrent illnesses, reactions to concurrent medications, or progression of disease states
Safety and Tolerability: Number of Patients Who Withdraw Due to TEAEs
时间窗: Day 1 to end of study (up to Day 182 [32 mg cohort]/ Day 210 [all other cohorts])
次要结局
- Pharmacodynamics(Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts))
- PK: Area Under the Plasma Concentration-time Curve (AUClast)(Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.)
- Pharmacokinetics (PK): Maximum Observed Concentration (Cmax)(Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.)
- PK: Terminal Elimination Half Life(Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.)
- PK: Time of Occurrence of Cmax (Tmax)(Patients participating in Period 1 (SAD) had PK samples collected on Day 1 predose through 24-48 hours postdose. Patients participating in Period 2 (MAD) had PK samples collected predose on Day 112 and through 4 hours postdose.)
- Clinical Effects: Total Functional Capacity (TFC)(Day 1 to last observation - up to Day 140 (32 mg cohort) or Day 196 (all other cohorts))