Study of SRP-1001 in Adult and Adolescent Participants With Facioscapulohumeral Muscular Dystrophy Type 1

• SRP-1001 for Injection (Drug), also known as ARO-DUX4 for Injection: Single or multiple doses of SRP-1001 by intravenous (IV) infusion
• Placebo (Drug): Calculated volume to match active treatment by IV infusion

Primary outcomes

• Number of Participants With Treatment-Emergent Adverse Events Over Time Through End of Study [Part 1: Up to Day 90; Part 2: Up to Day 360]

Secondary outcomes

• 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]

Sex: All, ages: 16 Years to 70 Years

Key Inclusion Criteria:

* 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.

Key Exclusion Criteria:

* 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

• Medical Director, Study director, Sarepta Therapeutics, Inc.

NIH grants: 2023