NCT05670730已完成1 期
A Phase 1/2, Randomized, Placebo-controlled, Double-blind, Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of Single and Multiple Ascending Doses of AOC 1044 Administered Intravenously to Healthy Adult Volunteers and Participants With DMD Mutations Amenable to Exon 44 Skipping
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 10
- 主要终点
- Incidence of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
AOC 1044-CS1 (EXPLORE44) is a Phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of single and multiple ascending doses of AOC 1044 in healthy adult volunteers and participants with DMD mutations amenable to exon 44 skipping.
Part A is a single dose design with multiple cohorts (dose levels) in healthy adult volunteers.
Part B is a multiple-ascending dose design with 3 cohorts (dose levels) in participants with Duchenne.
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
- 7 Years 至 55 Years（Child, Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Aged 18 to 55 years, inclusive, at the time of informed consent
- •Body mass index (BMI) of 18.5 to 32.0 kg/m2
排除标准
- •Clinically significant abnormalities in laboratory results, ECGs, or vitals
- •Current or recent use of prescription or nonprescription drugs
- •Positive drug/alcohol test at Screening or Day -1
- •Elevated blood pressure (BP) >130/80 mmHg at Screening
- •Participation in a clinical study in which an investigational product was received within 1 month of screening or 5 half-lives of the investigational product
- •Blood or plasma donation within 16 weeks of planned AOC 1044 administration Note: Other protocol defined Inclusion/Exclusion criteria may apply
- •Key Inclusion Criteria:
- •Aged 7 to 27 years, inclusive, at the time of informed consent
- •Clinical diagnosis of DMD or clear onset of DMD symptoms at or before the age of 6 years
- •Confirmation of DMD gene mutation amenable to exon 44 skipping
- •Weight ≥ 23 kg
- •Ambulatory or non-ambulatory
- •Ambulatory participants: LVEF ≥50% and FVC≥50%
- •Non-ambulatory participants: LVEF ≥45% and FVC≥40%
- •PUL 2.0 entry item A ≥3
- •If on corticosteroids, stable dose for 30 days before screening and throughout the study
- •Key Exclusion Criteria:
- •Biceps brachii muscles unsuitable for biopsy
- •Serum hemoglobin < lower limit of normal
- •Uncontrolled hypertension or diabetes
- •Prior treatment with any cell or gene therapy
- •Prior treatment with another exon 44 skipping agent within 6 months prior to informed consent
- •Recently treated with an investigational drug
- •History of multiple drug allergies
研究组 & 干预措施
AOC 1044-CS1 Part A - Single Dose Levels 1-5
Experimental
AOC 1044 will be administered once.
干预措施: AOC 1044 (Drug)
AOC 1044-CS1 Part A - Single Dose: Placebo
Placebo Comparator
Placebo will be administered once.
干预措施: Placebo (Drug)
AOC 1044-CS1 Part B - Multiple Ascending Dose Levels 1-3
Experimental
AOC 1044 will be administered three times.
干预措施: AOC 1044 (Drug)
AOC 1044-CS1 Part B - Multiple Ascending Dose: Placebo
Placebo Comparator
Placebo will be administered three times.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: Through study completion, up to Day 85 (Part A) or Day 169 (Part B)
次要结局
- Urine pharmacokinetic parameters(Day 1-2 (0-24 hours after first dose) (Part A); Day 1-2 (0-24 hours after first dose) (Part B))
- Plasma pharmacokinetic (PK) parameters(Through Week 8 (Part A); Through Week 12 (Part B))
- Change from baseline in exon skipping as measured in skeletal muscle (Part B only)(Baseline, Week 16)
- Percentage change from baseline in dystrophin protein level in skeletal muscle (Part B only)(Baseline, Week 16)
- PMO44 levels in skeletal muscle tissue(Through Week 4 (Part A); Through Week 16 (Part B))
- Absolute change from baseline in dystrophin protein level in skeletal muscle (Part B only)(Baseline, Week 16)
研究者
研究点 (10)
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