NCT06138743招募中1 期
A Phase 1/2a Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-DM1 (SRP-1003) in Subjects With Type 1 Myotonic Dystrophy Who Are ≥18 to ≤ 65 Years
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 78
- 试验地点
- 36
- 主要终点
- Number of Participants with Treatment-emergent Adverse Events Over Time Through End of Study (EOS)
研究概览
简要总结
This is a phase 1/2a double-blinded, placebo-controlled, dose-escalating study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of single and multiple ascending doses of SRP-1003 compared to placebo in male and female participants with type 1 myotonic dystrophy (DM1). Participants who have provided written informed consent and met all protocol eligibility requirements will be randomized to receive single (Part 1) or multiple (Part 2) doses of SRP-1003 or placebo.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Genetically confirmed diagnosis of DM1
- •Clinician-assessed signs of DM1 including clinically apparent myotonia
- •Onset of DM1 symptoms occurred after the age of 12 years
- •Walk for at least 10 meters independently at screening
- •Participants of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of study or last dose of study drug, whichever is later. Participants must not donate sperm or eggs during the study and for at least 90 days following the end of study or last dose of study drug whichever is later.
排除标准
- •Inadequately controlled diabetes
- •Confirmed diagnosis of congenital DM1
- •Uncontrolled hypertension
- •History of tibialis anterior (TA) biopsy within 3 months of Day 1 or planning to undergo TA biopsies during the study period
- •Clinically significant cardiac, liver or renal disease
- •Human immunodeficiency virus infection (seropositive) at screening
- •Seropositive for hepatitis B or hepatitis C at screening
- •Untreated or poorly controlled epilepsy
- •Treatment with anti-myotonia medication within a period of 5 half-lives of the medication prior to screening.
- •Abnormal coagulation parameters at screening including platelet count, international normalized ratio, prothrombin time, and activated partial thromboplastin time
- •Note: Additional inclusion/exclusion criteria may apply per protocol
研究组 & 干预措施
SRP-1003 IV Infusion
Experimental
Single or multiple doses of SRP-1003 by intravenous (IV) infusion
干预措施: SRP-1003 IV Infusion (Drug)
Placebo by IV Infusion
Placebo Comparator
Single or multiple doses of placebo by IV infusion
干预措施: Placebo IV Infusion (Drug)
SRP-1003 SC Injection
Experimental
Single or multiple doses of SRP-1003 by subcutaneous (SC) injection
干预措施: SRP-1003 SC Injection (Drug)
Placebo by SC Injection
Placebo Comparator
Single or multiple doses of placebo by SC injection
干预措施: Placebo SC Injection (Drug)
结局指标
主要结局
Number of Participants with Treatment-emergent Adverse Events Over Time Through End of Study (EOS)
时间窗: Single-dose phase (Part 1): Up to Day 90 (EOS); multiple-dose phase (Part 2): Up to Day 180 (EOS)
Number of Participants with Treatment -Emergent Adverse Events (TEAEs) Over Time Through End of Study (EOS)
时间窗: Single-dose phase (Part 1): Up to Day 90(EOS); multiple-dose phase (Part 2): Up to Day 180(EOS)
次要结局
- Change from Baseline Over Time for the Timed Up and Go Test (TUG) Assessment((Part 2): Baseline through EOS (up to 180 days))
- Change from Baseline Over Time for the Hand-held Quantitative Dynamometry Assessment((Part 2): Baseline through EOS (up to 180 days))
- Change from Baseline Over Time for the Video Hand Opening Time (vHOT) Assessment((Part 2): Baseline through EOS (up to 180 days))
- Change from Baseline Over Time for the Myotonic Dystrophy Type 1 Activity and Participation Scale (DM1-Activ-C) Assessment((Part 2): Baseline through EOS (up to 180 days))
- Change from Baseline Over Time for the Myotonic Dystrophy Health Index (MDHI) Assessment((Part 2): Baseline through EOS (up to 180 days))
- PK of SRP-1003: Maximum Observed Plasma Concentration (Cmax)(Single-dose phase (Part 1): Up 24 hours post-dose; multiple-dose phase (Part 2): Through 24 hours post first and second dose)
- PK of SRP-1003: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)(Single-dose phase (Part 1): Up 24 hours post-dose; multiple-dose phase (Part 2): Through 24 hours post first and second dose)
- PK of SRP-1003: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast)(Single-dose phase (Part 1): Up 24 hours post-dose; multiple-dose phase (Part 2): Through 24 hours post first and second dose)
- PK of SRP-1003: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUCinf)(Single-dose phase (Part 1): Up 24 hours post-dose; multiple-dose phase (Part 2): Through 24 hours post first and second dose)
- Change from Baseline Over Time for the Myotonic Dystrophy Health Index (MDHI) Assessment((Part 2): Baseline through EOS (up to 180 days))
- Pharmacokinetics (PK) of ARO-DM1: Maximum Observed Plasma Concentration (Cmax)(Single-dose phase (Part 1): Up 24 hours post-dose; multiple-dose phase (Part 2): Through 24 hours post first and second dose)
- PK of ARO-DM1: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)(Single-dose phase (Part 1): Up 24 hours post-dose; multiple-dose phase (Part 2): Through 24 hours post first and second dose)
- PK of ARO-DM1: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast)(Single-dose phase (Part 1): Up 24 hours post-dose; multiple-dose phase (Part 2): Through 24 hours post first and second dose)
- PK of ARO-DM1: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUCinf)(Single-dose phase (Part 1): Up 24 hours post-dose; multiple-dose phase (Part 2): Through 24 hours post first and second dose)
- Change from Baseline at Day 120 for Video Hand Opening Time (vHOT)((Part 2): Baseline, Day 120)
- Change from Baseline Over Time for the Timed Up and Go Test (TUG) Assessment((Part 2): Baseline through EOS (up to 180 days))
- Change from Baseline Over Time for the 10-Meter Walk/Run Test (10MWT) Assessment((Part 2): Baseline through EOS (up to 180 days))
- Change from Baseline Over Time for the Hand-held Quantitative Dynamometry Assessment((Part 2): Baseline through EOS (up to 180 days))
- Change from Baseline Over Time for the Video Hand Opening Time (vHOT) Assessment((Part 2): Baseline through EOS (up to 180 days))
- Change from Baseline Over Time for the Myotonic Dystrophy Type 1 Activity and Participation Scale (DM1-Activ-C) Assessment((Part 2): Baseline through EOS (up to 180 days))
研究者
研究点 (36)
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