Myotonic Dystrophy Type 1 (DM1)
Conditions
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 (168 weeks) in both multiple-ascending dose (MAD) and dose expansion cohorts.
Interventions
DRUGDYNE-101
Administered by IV infusion
DRUGPlacebo
Administered by IV infusion
Sponsors
Dyne Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
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
* 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 (MAD cohorts only), 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| MAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Through study completion, up to Week 217 |
| Dose Expansion Cohorts: Change From Baseline in Myotonia as Measured by Video Hand Opening Time (vHOT) | Baseline up to Week 25 |
Secondary
| Measure | Time frame |
|---|---|
| MAD Cohorts: Change From Baseline in Composite Alternative Splicing Index (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 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 217 |
| MAD Cohorts: Time to Maximum Observed Plasma Concentration (tmax) of DYNE-101 | Pre-dose, and at multiple timepoints up to Week 217 |
| 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 217 |
| 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 217 |
| MAD Cohorts: Apparent Terminal Elimination Rate Constant (λz) of DYNE-101 in Plasma | Pre-dose, and at multiple timepoints up to Week 217 |
| MAD Cohorts: Apparent Terminal Elimination Half-Life (t1/2) of DYNE-101 in Plasma | Pre-dose, and at multiple timepoints up to Week 217 |
| MAD Cohorts: Clearance (CL) of DYNE-101 in Plasma | Pre-dose, and at multiple timepoints up to Week 217 |
| MAD Cohorts: Volume of Distribution at the Terminal Phase (Vz) of DYNE-101 in Plasma | Pre-dose, and at multiple timepoints up to Week 217 |
| MAD Cohorts: Volume of Distribution at Steady State (Vss) of DYNE-101 in Plasma | Pre-dose, and at multiple timepoints up to Week 217 |
| 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 217 |
| Dose Expansion Cohorts: Change From Baseline in CASI in Skeletal Muscle Tissue | Baseline up to Week 25 |
| Dose Expansion Cohorts: Change From Baseline in QMT Total | Baseline up to Week 25 |
| Dose Expansion Cohorts: Change From Baseline in 10-MWRT | Baseline up to Week 25 |
| Dose Expansion Cohorts: Change From Baseline in 5×STS | Baseline up to Week 25 |
| Dose Expansion Cohorts: Change From Baseline in 9-HPT | Baseline up to Week 25 |
| Dose Expansion Cohorts: Change From Baseline in Myotonic Dystrophy Health Index (MDHI) Total Score | Baseline up to Week 25 |
| Dose Expansion Cohorts: Patient Global Impression of Change (PGI-C) | Baseline up to Week 25 |
| Clinician Global Impression of Change (CGI-C) | Baseline up to Week 25 |
| Dose Expansion Cohorts: Change From Baseline in Patient Global Impression of Severity (PGI-S) | Baseline up to Week 25 |
| Dose Expansion Cohorts: Change From Baseline in Clinician Global Impression of Severity (CGI-S) | Baseline up to Week 25 |
| Dose Expansion Cohorts: Change From Baseline in MDHI Subscale Scores | Baseline up to Week 25 |
| Dose Expansion Cohorts: Change From Baseline at in Myotonic Dystrophy type 1 Activity and Participation Scale (DM1-ACTIV^C) Total Score | Baseline up to Week 25 |
| Dose Expansion Cohorts: Change From Baseline in Percent Predicted Hand Grip Strength | Baseline up to Week 25 |
Countries
Australia, France, Germany, Italy, Netherlands, New Zealand, United Kingdom, United States
Contacts
CONTACTDyne Clinical Trials
Outcome results
None listed