A Phase 3, Randomized, Double-Blind, 48-Week Placebo-Controlled Study to Assess the Efficacy, Safety, and Tolerability of DYNE-101 Administered to Participants With Myotonic Dystrophy Type 1
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 37
- 主要终点
- 5 Times Sit-To-Stand (5×STS) Time
研究概览
简要总结
The purpose of the study is to assess the efficacy, safety, and tolerability of zeleciment basivarsen (DYNE-101) for the treatment of myotonic dystrophy 1 (DM1).
详细描述
The study consists of three periods: a Screening period (up to 8 weeks), Placebo-Controlled Period (48 weeks) and a Long-Term Extension Period (24 weeks).
An Independent Data Monitoring Committee (IDMC) comprised of members independent and external to the Sponsor will review safety and tolerability data of this study at regular intervals.
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of DM1 confirmed by molecular genetics with trinucleotide repeat size greater than (>)
- •Historical results from clinical testing are acceptable.
- •Able to walk 10 meters and complete 5 times sit to stand independently (inserts or supports that don't go above the ankle are allowed).
- •Body mass index (BMI) less than (<) 35 kilograms per meter square (kg/m^2).
排除标准
- •A known diagnosis of congenital DM
- •History of major surgical procedure (based on Investigator judgment) within 12 weeks prior to the start of screening, with the exception of implanted pacemaker or defibrillator.
- •Use of glucagon-like peptide 1 (GLP-1) agonist/incretin medications including semaglutide, dulaglutide, liraglutide, exenatide, or tirzepatide within a period of 5 half-lives of the medication prior to performing screening assessments.
- •Note: Other inclusion and exclusion criteria may apply.
研究组 & 干预措施
Placebo-Controlled Period: DYNE-101
Participants will be randomized to receive DYNE-101, once every 8 weeks (Q8W) for up to 48 weeks.
干预措施: zeleciment basivarsen (DYNE-101) (Drug)
Placebo-Controlled Period: Placebo
Participants will be randomized to receive DYNE-101 matching placebo, Q8W for up to 48 weeks.
干预措施: Placebo (Drug)
Long-Term Extension Period: DYNE-101
Participants who receive DYNE-101 in Placebo-Controlled Period will continue to received DYNE-101, Q8W for up to 24 weeks.
Participants who received placebo in Placebo-Controlled Period will receive DYNE-101, Q8W for up to 24 weeks.
干预措施: Placebo (Drug)
Long-Term Extension Period: DYNE-101
Participants who receive DYNE-101 in Placebo-Controlled Period will continue to received DYNE-101, Q8W for up to 24 weeks.
Participants who received placebo in Placebo-Controlled Period will receive DYNE-101, Q8W for up to 24 weeks.
干预措施: zeleciment basivarsen (DYNE-101) (Drug)
结局指标
主要结局
5 Times Sit-To-Stand (5×STS) Time
时间窗: Baseline, Week 49
次要结局
- Video Hand Opening Time (vHOT) [Middle Finger](Baseline, Week 49)
- Quantitative Muscle Testing (QMT) Total(Baseline, Week 49)
- Clinician Global Impression of Change (CGI-C)(Week 49)
- 10-Meter Walk/Run Test (10-MWRT) Velocity (m/s)(Baseline, Week 49)
- Patient Global Impression of Change (PGI-C)(Week 49)
- DM1-ACTIV^C Total Score(Baseline, Week 49)
- Myotonic Dystrophy Health Index (MDHI) Total(Baseline, Week 49)
- Patient Global Impression of Severity (PGI-S)(Baseline, Week 49)
- Clinician Global Impression of Severity (CGI-S)(Baseline, Week 49)
- 9-Hole Peg Test (9-HPT) Time(Baseline, Week 49)
- Myotonic Dystrophy Health Index (MDHI) Subscale Scores(Baseline, Week 49)
- Maximum Observed Plasma Drug Concentration (Cmax) of DYNE-101(Pre-dose, and at multiple time points up to Week 73)
- Time to Maximum Concentration (tmax) of DYNE-101(Pre-dose, and at multiple time points up to Week 73)
- Area Under the Concentration-Time Curve (AUC) from Hour 0 to the Last Measurable Concentration (AUC0-tlast) of DYNE-101(Pre-dose, and at multiple time points up to Week 73)
- Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-∞) of DYNE-101(Pre-dose, and at multiple time points up to Week 73)
- Apparent Terminal Elimination Rate Constant (λZ) of DYNE-101(Pre-dose, and at multiple time points up to Week 73)
- Apparent Terminal Elimination Half-Life (t½) of DYNE-101(Pre-dose, and at multiple time points up to Week 73)
- Plasma clearance (CL) of DYNE-101(Pre-dose, and at multiple time points up to Week 73)
- Volume of Distribution at the Terminal Phase (Vz), if Appropriate of DYNE-101(Pre-dose, and at multiple time points up to Week 73)
- Volume of Distribution at Steady State (Vss), if Appropriate of DYNE-101(Pre-dose, and at multiple time points up to Week 73)
- Number of Participants With Antidrug Antibodies (ADAs)(Up to Week 73)