A Randomized, Double-Blind, Placebo-Controlled, Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple-Doses of AOC 1001 Administered Intravenously to Adult Myotonic Dystrophy Type 1 (DM1) Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 8
- 主要终点
- Frequency of Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
AOC 1001-CS1 is a randomized, double-blind, placebo-controlled, Phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple-doses of AOC 1001 Administered Intravenously to Adult Myotonic Dystrophy Type 1 (DM1) patients (MARINA).
Part A is a single dose design with 1 cohort (dose level). In Part A, the patient duration is 6 months as the treatment period is 1 day followed by a 6 month follow-up period.
Part B is a multiple-ascending dose design with 2 cohorts (dose levels). In Part B, the patient duration is 6 months as the treatment period is 3 months followed by a 3 month follow-up period.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Genetic diagnosis of DM1 (CTG repeat length ≥ 100)
- •Clinician assessed signs of DM1
- •Ability to walk independently (orthoses and ankle braces allowed) for at least 10 meters at screening
排除标准
- •Diabetes that is not adequately controlled
- •BMI > 35 kg/m2
- •Uncontrolled hypertension
- •Congenital DM1
- •History of tibialis anterior (TA) biopsy within 3 months of Day 1 or planning to undergo TA biopsies during study period
- •Recently treated with an investigational drug
- •Treatment with anti-myotonic medication within 14 days of Day 1
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Part B Multiple Ascending Dose: Placebo
Saline will be administered three times.
干预措施: Placebo (Drug)
Part A Single Dose: Placebo
Saline will be administered once.
干预措施: Placebo (Drug)
Part A Single Dose: AOC 1001 Dose Level 1
AOC 1001 will be administered once.
干预措施: AOC 1001 (Drug)
Part B Multiple Ascending Dose: AOC 1001 Dose Levels 2 & 3
AOC 1001 will be administered three times.
干预措施: AOC 1001 (Drug)
结局指标
主要结局
Frequency of Treatment Emergent Adverse Events (TEAEs)
时间窗: Through study completion, up to Day 183
Cumulative number of participants with treatment emergent adverse events at the end of study.
Frequency of treatment emergent adverse events (TEAEs)
时间窗: Through study completion, up to Day 183
次要结局
- Plasma PK Parameters(Day 1)
- Plasma Pharmacokinetic (PK) Parameters(Day 1)
- Urine Pharmacokinetic (PK) Parameters(Day 1)
- Change From Baseline in DMPK mRNA Knockdown(Day 43 (participants treated with 1 mg/kg) and Day 92 (participants treated with 2 mg/kg and 4 mg/kg))
- Absolute Change From Baseline in 4 Gene Spliceopathy(Day 43 (participants treated with 1 mg/kg) and Day 92 (participants treated with 2 mg/kg and 4 mg/kg))
- AOC 1001 Concentration Levels in Plasma, Urine, and Muscle Tissue(Up to Day 43)
- Change and percentage change from baseline in DMPK mRNA knockdown(Through study completion, up to Day 183)
- Change and percentage change from baseline in Spliceopathy(Through study completion, up to Day 183)
- Urine pharmacokinetic (PK) parameters(Through study completion, up to Day 183)
- AOC 1001 levels in muscle tissue(Through study completion, up to Day 183)
- Plasma pharmacokinetic (PK) parameters(Through study completion, up to Day 183)