Myotonic Dystrophy 1
Conditions
Keywords
Myotonic Dystrophy 1, SRP-1003, ARO-DM1
Brief summary
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.
Interventions
DRUGSRP-1003 IV Infusion
SRP-1003 by IV infusion
0.9% sodium chloride (NaCl) calculated volume to match active treatment by IV infusion
DRUGSRP-1003 SC Injection
SRP-1003 by SC injection(s)
0.9% NaCl calculated volume to match active treatment by SC injection(s)
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
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * 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. Key
Exclusion criteria
* 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with Treatment-emergent Adverse Events Over Time Through End of Study (EOS) | Single-dose phase (Part 1): Up to Day 90 (EOS); multiple-dose phase (Part 2): Up to Day 180 (EOS) |
Secondary
| Measure | Time frame |
|---|---|
| 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 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) |
| Change from Baseline Over Time for the Myotonic Dystrophy Health Index (MDHI) Assessment | (Part 2): Baseline through EOS (up to 180 days) |
Countries
Australia, Belgium, Canada, France, Germany, Italy, New Zealand, Spain, Taiwan, Thailand, United Kingdom
Contacts
CONTACTSarepta Therapeutics Inc. For Clinical Trial Information, Select Option 4
STUDY_DIRECTORMedical Director
Sarepta Therapeutics, Inc.
Outcome results
None listed