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NCT05481879PHASE1, PHASE2Recruiting

Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-101 in Participants With Myotonic Dystrophy Type 1

Dyne Therapeutics

Start Date

9/5/2022

Completion Date

7/1/2029

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.

Eligibility Criteria

Age Range: 18 years to 65 years

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.

Interventions

DRUG

DYNE-101

DRUG

Placebo

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Conditions

Myotonic Dystrophy Type 1 (DM1)

Locations

Stanford University

Stanford, California 94305

United States

University of Florida College of Medicine

Gainesville, Florida 32610

United States

Indiana University School of Medicine

Indianapolis, Indiana 46202

United States

University of Iowa

Iowa City, Iowa 52242

United States

Washington University in St. Louis

St Louis, Missouri 63110

United States

University of Rochester Medical Center

Rochester, New York 14642

United States

Neurology Rare Disease Center

Denton, Texas 76208

United States

Virginia Commonwealth University (VCU)

Richmond, Virginia 23298

United States

St. Vincent's Hospital

Fitzroy, Victoria 3065

Australia

CHU de Nantes

Nantes, 44093

France

Institut de Myologie

Paris, 75013

France

Charité - Universitätsmedizin Berlin

Berlin, 10117

Germany

Ludwig Maximilians University, Munich - Friedrich Baur Institut

Munich, 80336

Germany

Centro Clinico Nemo

Milan, 20162

Italy

Fondazione Policlinico Universitario A Gemelli-Rome

Rome, 00168

Italy

Radboud Medical Center

Nijmegen,

Netherlands

NZCR Auckland

Auckland, 1023

New Zealand

University College London Hospitals

London, NW1 2BU

United Kingdom

John Walton Muscular Dystrophy Research Centre

Newcastle upon Tyne,

United Kingdom

Salford Royal Hospital

Salford, M6 8HD

United Kingdom