Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-101 in Participants With Myotonic Dystrophy Type 1
- Registration Number
- NCT05481879
- Lead Sponsor
- Dyne Therapeutics
- Brief Summary
The primary purpose of the study is to evaluate the safety and tolerability of multiple intravenous (IV) doses of DYNE-101 administered to participants with Myotonic Dystrophy Type 1 (DM1).
The study consists of 4 periods: A Screening Period (up to 8 weeks), a Placebo-Controlled Period (24 weeks), a Treatment Period (24 weeks) and a Long-Term Extension (LTE) Period (144 weeks) in both multiple-ascending dose (MAD) and dose expansion cohorts.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 72
Inclusion Criteria
- Diagnosis of DM1 with trinucleotide repeat size >100.
- Age of onset of DM1 muscle symptoms ≥12 years.
- Clinically apparent myotonia equivalent to hand opening time of at least 2 seconds in the opinion of the Investigator.
- Hand grip strength and ankle dorsiflexion strength.
- 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.
Exclusion Criteria
- 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 the study.
- History of anaphylaxis.
- Medical condition other than DM1 that would significantly impact ambulation or participation in functional assessments.
- Treatment with medications that can improve myotonia within a period of 5 half-lives of the medication prior to performing screening assessments.
- Electrocardiogram (ECG) with the corrected QT interval by Fridericia's Formula (QTcF) ≥450 milliseconds (ms) in men and QTcF ≥460 ms in women, PR ≥240 ms, left bundle-branch block, or a conduction defect, which is clinically significant in the opinion of the Investigator.
- Percent predicted forced vital capacity (FVC) <50%.
- 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.
- Participant has a history of suicide attempt, suicidal behavior, or has any suicidal ideation within 6 months prior to Screening that meets criteria at a level of 4 or 5 of the Columbia Suicide Severity Rating Scale (C-SSRS) or who, in the opinion of the Investigator, is at significant risk to commit suicide.
- Use of glucagon-like peptide 1 (GLP-1) agonist medications including semaglutide, dulaglutide, liraglutide, exenatide, or tirzepatide within a period of 5 half-lives of the medication prior to performing screening assessments.
- Significant weight loss during study participation may impact weight-based dosing, performance on muscle function assessments, and pharmacodynamic (PD) biomarkers.
Note: Other inclusion and exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description MAD Cohort: Placebo-Controlled Period: DYNE-101 DYNE-101 Participants will be randomized to receive ascending doses of DYNE-101, once every 4 weeks (Q4W) or once every 8 weeks (Q8W) for up to 24 weeks. MAD Cohort: Placebo-Controlled Period: Placebo Placebo Participants will be randomized to receive DYNE-101 matching placebo, Q4W or Q8W for up to 24 weeks. MAD Cohort: Treatment Period: DYNE-101 DYNE-101 Participants who receive DYNE-101 in Placebo-Controlled Period will continue to receive DYNE-101, Q4W or Q8W for up to 24 weeks. Participants who receive placebo in Placebo-Controlled Period will receive DYNE-101, Q4W or Q8W for up to 24 weeks. MAD Cohort: Treatment Period: DYNE-101 Placebo Participants who receive DYNE-101 in Placebo-Controlled Period will continue to receive DYNE-101, Q4W or Q8W for up to 24 weeks. Participants who receive placebo in Placebo-Controlled Period will receive DYNE-101, Q4W or Q8W for up to 24 weeks. MAD Cohort: Long-Term Extension Period: DYNE-101 DYNE-101 Participants will receive DYNE-101, Q4W or Q8W for up to 144 weeks. Dose Expansion Cohort: Placebo-Controlled Period: DYNE-101 DYNE-101 Participants will receive DYNE-101, Q8W for up to 24 weeks. Dose Expansion Cohort: Placebo-Controlled Period: Placebo Placebo Participants will receive DYNE-101 matching placebo, Q8W for up to 24 weeks. Dose Expansion Cohort: Treatment Period: DYNE-101 DYNE-101 Participants who receive DYNE-101 in Placebo-Controlled Period will continue to receive DYNE-101, Q8W for up to 24 weeks. Participants who receive placebo in Placebo-Controlled Period will receive DYNE-101, Q8W for up to 24 weeks. Dose Expansion Cohort: Treatment Period: DYNE-101 Placebo Participants who receive DYNE-101 in Placebo-Controlled Period will continue to receive DYNE-101, Q8W for up to 24 weeks. Participants who receive placebo in Placebo-Controlled Period will receive DYNE-101, Q8W for up to 24 weeks. Dose Expansion Cohort: Long-Term Extension Period: DYNE-101 DYNE-101 Participants will receive DYNE-101, Q8W for up to 144 weeks.
- Primary Outcome Measures
Name Time Method MAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Through study completion, up to Week 193 Dose Expansion Cohorts: Change From Baseline in Composite Alternative Splicing Index (CASI) in Skeletal Muscle Tissue up to Week 13 Baseline up to Week 13
- Secondary Outcome Measures
Name Time Method MAD Cohorts: Change From Baseline in CASI in Skeletal Muscle Tissue Baseline up to Week 45 MAD Cohorts: Change From Baseline in Dystrophia Myotonica Protein Kinase (DMPK) Ribonucleic Acid (RNA) Expression in Muscle Tissue Baseline up to Week 45 MAD Cohorts: Change From Baseline in Hand Grip Relaxation Time Baseline up to Week 121 MAD Cohorts: Change From Baseline in Myotonia as Measured by Video Hand Opening Time (vHOT) Baseline up to Week 193 MAD Cohorts: Change From Baseline in Quantitative Myometry Testing (QMT) Baseline up to Week 193 MAD Cohorts: Change From Baseline in 10-Meter Walk/Run Test (10-MWRT) Baseline up to Week 193 MAD Cohorts: Change From Baseline in Stair-Ascend/Descend Test Baseline up to Week 121 MAD Cohorts: Change From Baseline in 5 Times Sit to Stand (5×STS) Baseline up to Week 193 MAD Cohorts: Change From Baseline in 9-Hole Peg Test (9-HPT) Baseline up to Week 193 MAD Cohorts: Maximum Observed Plasma Drug Concentration (Cmax) of DYNE-101 Pre-dose, and at multiple timepoints up to Week 193 MAD Cohorts: Time to Maximum Observed Plasma Concentration (tmax) of DYNE-101 Pre-dose, and at multiple timepoints up to Week 193 MAD Cohorts: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Plasma Concentration (AUCtlast) of DYNE-101 Pre-dose, and at multiple timepoints up to Week 193 MAD Cohorts: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC∞) of DYNE-101 in Plasma Pre-dose, and at multiple timepoints up to Week 193 MAD Cohorts: Apparent Terminal Elimination Rate Constant (λz) of DYNE-101 in Plasma Pre-dose, and at multiple timepoints up to Week 193 MAD Cohorts: Apparent Terminal Elimination Half-Life (t1/2) of DYNE-101 in Plasma Pre-dose, and at multiple timepoints up to Week 193 MAD Cohorts: Clearance (CL) of DYNE-101 in Plasma Pre-dose, and at multiple timepoints up to Week 193 MAD Cohorts: Volume of Distribution at the Terminal Phase (Vz) of DYNE-101 in Plasma Pre-dose, and at multiple timepoints up to Week 193 MAD Cohorts: Volume of Distribution at Steady State (Vss) of DYNE-101 in Plasma Pre-dose, and at multiple timepoints up to Week 193 MAD Cohorts: Antisense Oligonucleotide (ASO) Concentration of DYNE-101 in Muscle Tissue Up to Week 45 MAD Cohorts: Number of Participants With Antidrug Antibodies (ADAs) Up to Week 193 Dose Expansion Cohorts: Change From Baseline in Myotonia as Measured by vHOT up to Week 25 Baseline up to Week 25 Dose Expansion Cohorts: Change From Baseline in 10-MWRT up to Week 25 Baseline up to Week 25 Dose Expansion Cohorts: Change From Baseline in QMT up to Week 25 Baseline up to Week 25 Dose Expansion Cohorts: Change From Baseline in 5×STS up to Week 25 Baseline up to Week 25 Dose Expansion Cohorts: Change From Baseline in Myotonic Dystrophy Health Index (MDHI) Total Score up to Week 25 Baseline up to Week 25
Trial Locations
- Locations (9)
Institut de Myologie
🇫🇷Paris, France
Ludwig Maximilians University, Munich - Friedrich Baur Institut
🇩🇪Munich, Germany
Centro Clinico Nemo
🇮🇹Milan, Italy
Fondazione Policlinico Universitario A Gemelli-Rome
🇮🇹Rome, Italy
Radboud Medical Center
🇳🇱Nijmegen, Netherlands
NZCR Auckland
🇳🇿Auckland, New Zealand
University College London Hospitals
🇬🇧London, United Kingdom
John Walton Muscular Dystrophy Research Centre
🇬🇧Newcastle-Upon-Tyne, United Kingdom
Salford Royal Hospital
🇬🇧Salford, United Kingdom