Muscular Dystrophy, Facioscapulohumeral
Conditions
Keywords
Facio-Scapulo-Humeral Muscular Dystrophy, SRP-1001, ARO-DUX4
Brief summary
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.
Interventions
DRUGSRP-1001 for Injection
Single or multiple doses of SRP-1001 by intravenous (IV) infusion
DRUGPlacebo
Calculated volume to match active treatment by IV infusion
Sponsors
Sarepta Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
Countries
Australia, Canada, Germany, Italy, Netherlands, New Zealand, Spain
Contacts
CONTACTSarepta Therapeutics Inc. For Clinical Trial Information, Select Option 4
STUDY_DIRECTORMedical Director
Sarepta Therapeutics, Inc.
Outcome results
None listed