NCT06131983招募中1 期
A Phase 1/2a Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-DUX4 (SRP-1001) in Adult Patients and Adolescent Patients With Facioscapulohumeral Muscular Dystrophy Type 1
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
- 60
- 试验地点
- 33
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events Over Time Through End of Study
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of SRP-1001 in participants with facioscapulohumeral muscular dystrophy Type 1 (FSHD1). In Part 1 of the study, participants will receive one dose of SRP-1001 or placebo. In Part 2 of the study, participants will receive 4 doses of SRP-1001 or placebo. Participants who complete Part 1 will have the option to re-screen and re-randomize into Part 2. All participants will undergo pre- and post-dose magnetic imaging resonance (MRI)-guided muscle biopsies (a total of 2 biopsies). Participants who complete Part 1 and enroll in Part 2 will be required to undergo an additional screening biopsy. Participants completing Part 1 or Part 2 may have the option to continue to receive drug in an open-label extension study or may be eligible to participate in later-stage clinical studies.
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 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Genetically confirmed FSHD1 based on screening evaluation or source verifiable medical record
- •Clinical severity score between 3 and 8 (scale, 0 to 10)
- •Must have an eligible lower extremity muscle for biopsy as determined from MRI by a central reader, with muscle fat fraction ≥10% and less than approximately 40%
- •Males or nonpregnant, nonlactating females ≥18 years of age who do not plan to become pregnant during the study, with an upper age limit of ≤70 years
- •Able and willing to provide written informed consent prior to the performance of any study specific procedures
- •Participants with a body mass index (BMI) between 18.0 and 35.0 kilograms/square meter, inclusive. A participant with FSHD1 and a BMI outside this range may be allowed into the study at the discretion of the principal investigator.
- •Must have eligible lower extremity muscle for biopsy as determined from MRI by a central reader
- •A 12-lead electrocardiogram at screening with no abnormalities that may compromise participant's safety in the study
- •Participants of childbearing potential and their partners must use highly effective contraception during the study and for at least 9 months following the end of study or last dose of study medication, whichever is later. Males must not donate sperm during the study from Day 1 until at least 9 months following the end of study or last dose of study medication, whichever is later.
排除标准
- •Human immunodeficiency virus (HIV) infection as shown by presence of anti-HIV antibody (seropositive) at screening
- •Seropositive for hepatitis B or hepatitis C at screening
- •Uncontrolled hypertension
- •Severe cardiovascular disease
- •History of thrombolic events
- •Platelet count less that the lower limit of normal at screening
- •History or presence of: a hypercoagulable state, nephrotic range proteinuria, antiphospholipid antibody syndrome, myeloproliferative disease, inability to ambulate, use of hormone-based contraceptives.
- •Any contraindication to muscle biopsy or MRI
- •Note: additional inclusion/exclusion criteria may apply per protocol
研究组 & 干预措施
Placebo
Placebo Comparator
Sodium chloride (0.9%)
干预措施: Placebo (Drug)
SRP-1001
Experimental
SRP-1001 for injection
干预措施: SRP-1001 for Injection (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events Over Time Through End of Study
时间窗: Part 1: Up to Day 90; Part 2: Up to Day 360
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Over Time Through End of Study (EOS)
时间窗: Part 1: Up to Day 90; Part 2: Up to Day 360
次要结局
- PK of SRP-1001: Maximum Observed Plasma Concentration (Cmax)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of SRP-1001: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of SRP-1001: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of SRP-1001: Area Under the Plasma Concentration Versus Time from Zero to Infinity (AUCinf)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of SRP-1001: Terminal Elimination Half-Life (t1/2)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of SRP-1001: Systemic Clearance (CL)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of SRP-1001: Volume of Distribution (Vss)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of SRP-1001: Recovery of Unchanged Drug in Urine Over 0-24 Hours (Amount Excreted: Ae)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of SRP-1001: Fraction of Drug Excreted in Urine as Percent of IV Dose (Fe)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of SRP-1001: Renal Clearance (CLr)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- Pharmacokinetics (PK) of ARO-DUX4: Maximum Observed Plasma Concentration (Cmax)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of ARO-DUX4: Area Under the Plasma Concentration Versus Time from Zero to Infinity (AUCinf)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of ARO-DUX4: Terminal Elimination Half-Life (t1/2)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of ARO-DUX4: Systemic Clearance (CL)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of ARO-DUX4: Volume of Distribution (Vss)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of ARO-DUX4: Recovery of Unchanged Drug in Urine Over 0-24 Hours (Amount Excreted: Ae)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of ARO-DUX4: Fraction of Drug Excreted in Urine as Percent of Intravenous (IV) Dose (Fe)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
- PK of ARO-DUX4: Renal Clearance (CLr)(Part 1: through 48 hours post-dose (all cohorts) and through 48 hours post second dose (Cohorts 3 & 4 only); Part 2: through 8 hours post first and second dose)
研究者
研究点 (33)
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