Efficacy and Safety of DYNE-101 in Participants with Myotonic Dystrophy Type 1: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study

Trial ID: 2025-522957-20-00
Protocol: DYNE101-DM1-301
Sponsor: Dyne Therapeutics Inc.

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Diseases & Conditions

Myotonic dystrophy

Objectives

The primary objective of this study is to evaluate the efficacy of DYNE-101 compared to a placebo in improving muscle function in individuals with myotonic dystrophy type 1. Secondary objectives include:

Evaluation of efficacy through improvements in muscle parameters, specifically myotonia, and participant-reported outcomes.
Assessment of plasma pharmacokinetics.
Evaluation of immunogenicity.
Assessment of safety and tolerability.

Participants

This clinical trial involves 78 participants diagnosed with myotonic dystrophy type 1. The study population includes both male and female patients, including vulnerable populations, within specific age ranges. Eligible individuals must have a diagnosis confirmed by molecular genetics with a trinucleotide repeat size greater than 100. Clinical requirements include myotonia equivalent to a hand opening time of at least 3 seconds and a hand grip strength between 15% and 85% of the predicted normal. Participants must be able to complete the 5-times sit-to-stand test and the 10-meter walk test without assistive devices such as canes or walkers. Additional criteria require a body mass index of less than 35kg/m2 and, if applicable, a stable dose of testosterone replacement therapy for 30 days prior to screening.

Plans and Procedures

This Phase 3, randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy, safety, and tolerability of DYNE-101 in participants diagnosed with myotonic dystrophy type 1. The research methodology involves comparing the effects of the test product against a placebo over a 48-week period. The study begins with a screening visit to confirm eligibility through molecular genetics, assessment of myotonia via hand opening time, and evaluation of muscle function including hand grip strength and 5×STS. Following screening, participants will undergo scheduled visits for intravenous use administration and various assessments to monitor primary endpoints and secondary endpoints. The total duration of participant involvement is approximately 48 weeks. Potential reasons for early termination from the study include treatment-emergent adverse events or discontinuation from the study drug.

Treatment

DYNE-101 is an experimental injection or infusion consisting of a humanised IgG1 kappa fragment antibody targeting TfR1 conjugated to p125 oligonucleotide. The administration of this orphan drug is conducted via intravenous use at a dosage of 99 mg/kg for the treatment of myotonic dystrophy type 1.

The placebo, identified as sodium chloride, contains potassium chloride Ph. Eur., sodium hydrogen carbonate Ph. Eur., and sodium chloride Ph. Eur. This substance is administered through intravenous use.

Efficacy

The primary efficacy endpoint is the change from baseline in the 5×STS time at Week 49. This parameter is utilized to assess improvements in muscle function in participants with myotonic dystrophy type 1.

Secondary efficacy parameters evaluated at Week 49 include changes from baseline in the following measures:

vHOT
middle finger QMT
total CGI-C
10-MWRT velocity
PGI-C
DM1-ACTIVC total score
MDHI total
PGI-S
CGI-S
9-HPT
MDHI subscale

Inclusion and Exclusion Criteria

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Inclusion Criteria

Age 16 to ≤ 65 years at the time of signing the informed consent/assent form
Capable of giving signed informed consent/assent as described in the protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol and authorization to use health information that is confidential according to national and local privacy regulations
Willingness and ability of participant to comply with and tolerate scheduled visits, dosing administration plan, and study assessments over the duration of the study
Diagnosis of DM1 confirmed by molecular genetics with trinucleotide repeat size > 100. Historical results from clinical testing are acceptable
Clinically apparent myotonia equivalent to hand opening time of at least 3 seconds as determined by a central reading of vHOT (middle finger) values
Hand grip strength averaged from both sides ≥ 15% and ≤ 85% predicted of normal
5×STS completion in ≥ 8 seconds without the use of assistive devices such as canes or walkers. The use of braces, such as ankle braces, and orthoses such as submalleolar orthoses, and inserts or supports that do not extend above the malleolus are permitted during testing.
Able to complete 10-MWRT and 5×STS 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
Body mass index (BMI) < 35kg/m2
If being treated with testosterone, on a stable replacement dose for 30 days prior to screening
Participants must agree to follow protocol-specified highly effective contraception guidance as described in the protocol

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Exclusion Criteria

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 the dosing schedule and follow-up will be correctly completed, and/or impair the assessment and interpretation of study results
Persistent systolic blood pressure < 90 mm Hg or signs or symptoms of hypotension or volume depletion/dehydration
Use of nephrotoxic medications within a period of 5 half-lives of the medication prior to performing screening assessments. These may include, but are not limited to, nonsteroidal anti-inflammatory drugs (NSAIDs), aminoglycosides (eg, gentamicin and streptomycin), bisphosphonates, and antiviral agents (eg, acyclovir and adefovir). Planned procedures that require contrast during the study are also exclusionary
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 thathat has been successfully excised and considered cured at least 1 year prior to Screening. Participants with cancers in remission for >5 years prior to Screening may be included after discussion with the Medical Monitor.
Receipt of any prior gene therapy, or 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
Percent predicted forced vital capacity (FVC) < 50% (sitting position)
Recent physical inactivity (eg, immobilization of ≥ 3 days) if, in the opinion of the Investigator, this would hinder the participant from complying with study requirements
Inability to undergo venipuncture successfully or tolerate venous access
Inability, or impaired ability, to complete study procedures and/or complete the study, due to physical or cognitive impairment or illicit drug or alcohol abuse, in the judgment of the Investigator
Medical condition other than DM1 that would significantly impact ambulation or participation in functional assessments
Uncontrolled diabetes mellitus or other serious medical illness that may complicate interpretation of safety or efficacy in the study, in the opinion of the Investigator
Use of glucagon-like peptide 1 (GLP-1) agonist/incretin medications including semaglutide, dulaglutide, liraglutide, exenatide, or tirzepatide within a period of 5 half-lives of the medication prior to performing screening assessments
Individuals with a history or presence of second- or third-degree heart block, ventricular arrhythmias, 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 bundle-branch block, or a conduction defect that is clinically significant in the opinion of the Investigator are excluded unless they have an implanted pacemaker or defibrillator that was implanted more than 2 weeks prior to screening
Individuals with known structural heart disease, evidence of noncompaction cardiomyopathy, or a known (at most recent imaging) left ventricular ejection fraction of < 40%
Individual 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 document or who, in the opinion of the Investigator, is at significant risk to commit suicide
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. ay include, but not limited to, mexiletine, phenytoin, carbamazepine, procainamide, disopyramide, ranolazine, flecainide, lamotrigine, nifedipine, acetazolamide, clomipramine, imipramine, amitriptyline, taurine, or quinine
Current treatment with systemic immunosuppressive therapy
A known diagnosis of congenital DM1
History of major surgical procedure (based on Investigator judgment) within 12 weeks prior to the start of screening, with the exception of implanted pacemaker or defibrillator, or an expectation of a major surgical procedure during the Placebo-Controlled Period of the study (based on Investigator judgment).
History of DVT or PE within the last 5 years
History of clinically significant liver disease or ongoing treatment for liver disease or confirmed elevated ALT > 3× ULN at screening
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
History of clinically significant kidney disease, ongoing treatment for kidney disease (treatment for hypertension is permitted) or eGFR < 60 mL/min as calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Cystatin C Equation
Acute kidney injury within 12 weeks prior to Screening, characterized by an increase in serum creatinine of 0.3 mg/dL within 48 hours, or of 1.5-fold within a week
Hematuria > 5 red blood cells per high power field (RBC/HPF) on urinalysis at screening
Inability to comply with physical activity requirements (eg., abstaining from strenuous exercise) from Screening through the end of the Placebo-Controlled Period
Any participant who is pregnant or breastfeeding or is planning to become pregnant during the study

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Belgium	Recruiting	30 Apr 2026	6
Denmark	Recruiting	30 Apr 2026	6
France	Recruiting	30 Apr 2026	15
Germany	Recruiting	30 Apr 2026	18
Italy	Not Yet Recruiting	30 Apr 2026	15
The Netherlands	Not Yet Recruiting	30 Apr 2026	—
Spain	Recruiting	30 Apr 2026	6
Netherlands	—	—	6