Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-101 in Participants with Myotonic Dystrophy Type 1
- Conditions
- Myotonic Dystrophy Type 1MedDRA version: 20.0Level: PTClassification code: 10068871Term: Myotonic dystrophy Class: 100000004850Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- CTIS2023-510353-42-00
- Lead Sponsor
- Dyne Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 79
Age 1. Age 18 to < 50 years, at the time of signing the informed consent. Type of Participant and Disease Characteristics 2. Diagnosis of DM1 confirmed by molecular genetics with trinucleotide repeat size > 100. Historical results from clinical testing are acceptable 3. Age of onset of DM1 muscle symptoms = 12 years 4. Clinically apparent myotonia equivalent to hand opening time of at least 2 seconds in the opinion of the Investigator 5. Hand grip strength and ankle dorsiflexion strength a. Hand grip strength averaged from both sides = 20% and = 80% (±5%) predicted for age, sex, and height at screening b. Ankle dorsiflexion strength averaged from both sides = 20% and =80% (± 10%) predicted for age, sex, and height at screening Note: Two sets of functional assessments must be performed during the Screening Period. Participants must meet inclusion criterion #5 on both sets of functional assessments for study eligibility 6. Able to complete 10-MWRT, stair ascend/descend, and 5×STS at screening without the use of assistive devices such as canes, walkers, or orthoses. The use of submalleolar orthoses and inserts or supports that do not extend above the malleolus are permitted during testing 7. Body mass index (BMI) < 35kg/m2 8. If being treated with testosterone, on a stable replacement dose for 30 days prior to screening Sex and Contraceptive/Barrier Requirements 9. Participants must agree to follow protocol-specified contraception guidance 10. Female participants must not be pregnant or breastfeeding Informed Consent 11. Capable of giving signed informed consent in compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol Other Inclusions 12. Willingness and ability of participant to comply with and tolerate scheduled visits, dosing administration plan, and study assessments, including multiple needle muscle biopsy procedures over the duration of the study 13. For France Only: According to the Article L1124-1 of the French Public Health Code, only individuals with social security or similar coverage are eligible for this study
1. Previous or ongoing medical condition, medical history, physical findings, or laboratory abnormalities that in the opinion of the Investigator could affect safety, make it unlikely that dosing schedule and follow-up will be correctly completed, and/or impair the assessment and interpretation of study results 2. History of major surgical procedure within 12 weeks prior to the start of investigative product administration or an expectation of a major surgical procedure (eg, implantation of cardiac defibrillator) during course of the study 3. History of anaphylaxis 4. History of clinically significant liver disease or ongoing treatment for liver disease 5. History of clinically significant hematologic disease or have any of the following hematologic results at Screening: platelets or hemoglobin below the lower limit of normal for age and sex. 6. History of clinically significant kidney disease, ongoing treatment for kidney disease (treatment for hypertension is permitted) or estimated glomerular filtration rate (eGFR) < 60 mL/min as calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Cystatin C Equation at screening 7. Active malignancy or history within the last 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated 8. Recent history (within previous 12 months) of drug or alcohol abuse 9. Medical condition other than DM1 that would significantly impact ambulation or participation in functional assessments 10. Current insulin-dependent diabetes mellitus or uncontrolled diabetes mellitus, congestive heart failure, symptomatic cardiomyopathy, symptomatic coronary artery disease, multiple sclerosis, or other serious medical illness, 11. Second- or third-degree heart block, symptomatic first-degree heart block, atrial flutter, atrial fibrillation, ventricular arrhythmias, pacemakers, implanted defibrillator, or is receiving medication for treatment of cardiac arrhythmia 12. Treatment with medications that can improve myotonia or clinical functional endpoints within a period of 5 half-lives of the medication prior to performing screening assessments. May include but not limited to mexiletine, phenytoin, carbamazepine, procainamide, disopyramide, ranolazine, flecainide, lamotrigine, nifedipine, acetazolamide, clomipramine, imipramine, amitriptyline, taurine, quinine, or metformin. 13. Use of anticoagulant such as warfarin or a direct oral anticoagulant (eg, dabigatran) due to the increased risk of bleeding 14. Current treatment with immunosuppressive therapy 15. Receipt of another investigational drug, biologic agent, or device within 5 half-lives (if known) of the agent, or within 4 months prior to the start of Screening, whichever is longer. Individuals previously treated with oligonucleotide therapies (including small interfering RNA [siRNA]) may be eligible if the last dose of the investigational drug was received = 3 years ago 16. ECG with the corrected QT interval by Fridericia's Formula (QTcF) =450 ms in men and QTcF = 460 ms in women, PR = 240 ms, left bundlebranch block, or a conduction defect, which is clinically significant in the opinion of the Investigator 17. Percent predicted forced vital capacity (FVC) < 50% 18. History of tibialis anterior biopsy within 3 months of Day 1 or planning to undergo tibialis anterior biopsies during study period for reasons unrelated to the study 19. Inability, or impaired ability, to complet
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the safety and tolerability of multiple IV doses of DYNE-101 administered to participants with DM1;Secondary Objective: To evaluate the effect of multiple intravenous doses of DYNE-101 administered to participants with DM1 on muscle tissue To evaluate change in muscle parameters after multiple doses of DYNE-101 administered to participants with DM1 To evaluate plasma and muscle tissue PK following multiple intravenous doses of DYNE-101 administered to participants with DM1 To evaluate the immunogenicity of multiple intravenous doses of DYNE-101 administered to participants with DM1;Primary end point(s): Number and proportion of participants with treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), TEAEs considered related to study drug, and TEAEs leading to discontinuation from study drug and discontinuation from the study
- Secondary Outcome Measures
Name Time Method