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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
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 exclusion criteria may apply.
Primary outcome measure(s)
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
Trial sites (20)
Facility
City
Region
Status
Stanford University
Stanford
California
Recruiting
University of Florida College of Medicine
Gainesville
Florida
Recruiting
Indiana University School of Medicine
Indianapolis
Indiana
Recruiting
University of Iowa
Iowa City
Iowa
Recruiting
Washington University in St. Louis
St Louis
Missouri
Recruiting
University of Rochester Medical Center
Rochester
New York
Recruiting
Neurology Rare Disease Center
Denton
Texas
Recruiting
Virginia Commonwealth University (VCU)
Richmond
Virginia
Recruiting
St. Vincent's Hospital
Fitzroy
Victoria
Recruiting
CHU de Nantes
Nantes
France
Recruiting
Institut de Myologie
Paris
France
Recruiting
Charité - Universitätsmedizin Berlin
Berlin
Germany
Recruiting
Ludwig Maximilians University, Munich - Friedrich Baur Institut
Munich
Germany
Recruiting
Centro Clinico Nemo
Milan
Italy
Recruiting
Fondazione Policlinico Universitario A Gemelli-Rome
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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