A Randomized, Double-blind, Placebo-controlled, Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of AOC 1020 Administered Intravenously to Participants With Facioscapulohumeral Muscular Dystrophy (FSHD)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 34
- 主要终点
- Incidence of treatment-emergent adverse events (Cohorts A & B)
研究概览
简要总结
A Randomized, Double-blind, Placebo-controlled, Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of AOC 1020 Administered Intravenously to Participants with Facioscapulohumeral Muscular Dystrophy (FSHD)
详细描述
AOC 1020-CS1 is a first-in-human, 3-part, multi-center, Phase 1/2, randomized, double-blind, placebo-controlled study designed to evaluate safety, tolerability, pharmacokinetics and to explore pharmacodynamics and efficacy of single and multiple-doses of AOC 1020 administered intravenously in participants with FSHD Type 1 (FSHD1) and FSHD Type 2 (FSHD2).
Cohort A comprises a placebo-controlled dose titration cohort (Cohort A1) which includes a nested single and multiple dose schedule. Cohort B comprises a placebo-controlled, nested single ascending dose (SAD)/multiple ascending dose (MAD) cohort (Cohort B1). Cohort C comprises a randomized, placebo-controlled, expansion cohort (Cohort C1). For each of Cohorts A, B, and C the study duration is 12 months as the active treatment period is approximately 9 months for Cohorts A & B and approximately 10.5 months for Cohort C followed by a 12-week follow-up period for Cohorts A & B and a 7-week follow-up period for Cohort C. Once participants have completed active treatment with follow-up through 12 months, they may have the option to participate in a planned open-label extension. If patients do not immediately roll over into the open-label extension study or decline participation, they will be followed for 18 weeks after their last dose of study medication.
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
- 16 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •FSHD1 or FSHD2 diagnosis confirmed by documented genetic testing (testing provided by Sponsor)
- •Ambulatory and able to walk 10 meters (with or without assistive devices such as one cane, walking stick or braces)
- •At least 1 muscle region suitable for biopsy (testing provided by Sponsor)
- •Muscle weakness in both upper and lower body, as determined by Investigator
排除标准
- •Pregnant or intends to become pregnant while on study, or active breastfeeding
- •Unwilling or unable to continue to comply with contraceptive requirements
- •Body mass index (BMI) >35.0 kg/m2 at Screening
- •History of muscle biopsy within 30 days of the screening biopsy or planning to undergo any nonstudy muscle biopsies over the duration of the study
- •History of bleeding disorders, significant keloid, or other skin or muscle conditions (e.g., severe muscle wasting) that, in the opinion of the Investigator, makes the participant unsuitable for serial muscle biopsy
- •Anticipated survival less than 2 years
- •Blood or plasma donation within 16 weeks of Study Day 1
- •Any contraindication to MRI
- •Any abnormal lab values, conditions or diseases that, in the opinion of the investigator or Sponsor, would make the participant unsuitable for the study or could interfere with participation or completion of the study
- •Treatment with any investigative medication within 1 month (or 5 half-lives of the drug, whichever is longer) of Screening
研究组 & 干预措施
AOC 1020 Regimen 1
Cohort A: AOC 1020 Dose Regimen 1; Five doses administered intravenously over 9 months
干预措施: AOC 1020 (Drug)
AOC 1020 Regimen 2
Cohort B1: AOC 1020 Dose Regimen 2; Five doses administered intravenously over 9 months
干预措施: AOC 1020 (Drug)
AOC 1020 Regimen 3
Cohort C: AOC 1020 Dose Regimen 3; Eight doses administered intravenously over approximately 10 months
干预措施: AOC 1020 (Drug)
Placebo (Saline) Regimen 1
Cohort A & B: Placebo; Five doses administered intravenously over 9 months
干预措施: Placebo (Drug)
Placebo (Saline) Regimen 2
Cohort C: Placebo; Eight doses administered intravenously over approximately 10 months
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events (Cohorts A & B)
时间窗: Through study completion, up to Day 365
Change in DUX4-regulated gene expression in muscle biopsies (Cohort C)
时间窗: Day 120
Change in a circulating biomarker of FSHD disease biology (Cohort C)
时间窗: Day 120
Change in plasma KHDC1L (Part C)
时间窗: Across months 3 to 12
Ratio to Baseline
次要结局
- Muscle drug concentration (Cohorts A, B & C)(Day 120)
- % Change in circulating creatine kinase (Cohort C)(Through study completion; up to Day 365)
- Change in DUX4-regulated gene expression in muscle biopsies (Cohort C)(Day 120)
- Plasma pharmacokinetic (PK) parameters of AOC 1020 (Cohorts A & B)(Through study completion; up to Day 365)
- Muscle drug concentration (Cohorts A & B)(Day 120)
- Change in circulating creatine kinase (Cohort C)(Across months 3 to 12)