Efficacy, Safety, and Tolerability of DYNE-101 in Participants with Myotonic Dystrophy Type 1

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dyne Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-04-28

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Dyne Therapeutics, Inc

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Efficacy

To evaluate the efficacy of DYNE 101 compared with placebo as measured by improvement in muscle function

Secondary objectives 4

1. 1. To evaluate the efficacy of DYNE101 compared with placebo as measured by improvement in muscle parameters including myotonia, and participant-reported outcomes
2. 2. To evaluate the plasma PK of DYNE-101
3. 3. To evaluate the immunogenicity of DYNE-101
4. 4. To evaluate the safety and tolerability of DYNE-101

Conditions and MedDRA coding

Myotonic Dystrophy Type 1

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. Age 16 to ≤ 65 years at the time of signing the informed consent/assent form
2. 11. 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
3. 12. Willingness and ability of participant to comply with and tolerate scheduled visits, dosing administration plan, and study assessments over the duration of the study
4. 2. Diagnosis of DM1 confirmed by molecular genetics with trinucleotide repeat size > 100. Historical results from clinical testing are acceptable
5. 3. Clinically apparent myotonia equivalent to hand opening time of at least 3 seconds as determined by a central reading of vHOT (middle finger) values
6. 4. Hand grip strength averaged from both sides ≥ 15% and ≤ 85% predicted of normal
7. 5. 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.
8. 6. 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
9. 7. Body mass index (BMI) < 35kg/m2
10. 8. If being treated with testosterone, on a stable replacement dose for 30 days prior to screening
11. 9. Participants must agree to follow protocol-specified highly effective contraception guidance as described in the protocol

Exclusion criteria 27

1. 1. 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
2. 10. Persistent systolic blood pressure < 90 mm Hg or signs or symptoms of hypotension or volume depletion/dehydration
3. 20. 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
4. 11. 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.
5. 21. 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
6. 22. Percent predicted forced vital capacity (FVC) < 50% (sitting position)
7. 23. 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
8. 24. Inability to undergo venipuncture successfully or tolerate venous access
9. 25. 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
10. 12. Medical condition other than DM1 that would significantly impact ambulation or participation in functional assessments
11. 13. 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
12. 19. 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
13. 14. 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
14. 15. Individuals with known structural heart disease, evidence of noncompaction cardiomyopathy, or a known (at most recent imaging) left ventricular ejection fraction of < 40%
15. 16. 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
16. 17. 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
17. 18. Current treatment with systemic immunosuppressive therapy
18. 4. A known diagnosis of congenital DM1
19. 2. 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).
20. 3. History of DVT or PE within the last 5 years
21. 5. History of clinically significant liver disease or ongoing treatment for liver disease or confirmed elevated ALT > 3× ULN at screening
22. 6. 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
23. 7. 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
24. 8. 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
25. 9. Hematuria > 5 red blood cells per high power field (RBC/HPF) on urinalysis at screening
26. Inability to comply with physical activity requirements (eg., abstaining from strenuous exercise) from Screening through the end of the Placebo-Controlled Period
27. Any participant who is pregnant or breastfeeding or is planning to become pregnant during the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 5×STS time, change from baseline at Week 49

Secondary endpoints 4

1. Change from baseline at Week 49 in: vHOT; middle finger QMT total CGI-C 10-MWRT velocity (m/s) PGI-C DM1-ACTIVC total score MDHI total PGI-S CGI-S 9-HPT MDHI subscale
2. Maximum observed drug concentration (Cmax) Time to maximum concentration (tmax) Area under the concentration-time curve (AUC) from hour 0 to the last measurable concentration (AUCtlast) AUC extrapolated to infinity (AUC∞) Apparent terminal elimination rate constant (λZ) Apparent terminal elimination half-life (t½) Plasma clearance (CL) Volume of distribution at the terminal phase (Vz), if appropriate Volume of distribution at steady state (Vss), if appropriate
3. Incidence of anti-drug antibodies (ADAs)
4. * Treatment-emergent adverse events (TEAEs) including: - Treatment-emergent serious adverse events (SAEs) - TEAEs considered related to study drug - TEAEs leading to discontinuation from study drug and discontinuation from the study * Other clinically significant safety and tolerability observations including: - Vital sign findings - 12-lead electrocardiogram (ECG) findings -Clinical laboratory values *C-SSRS results

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dyne Therapeutics Inc.

Sponsor organisation

Dyne Therapeutics Inc.

Address

1560 Trapelo Road

City

Waltham

Postcode

02451-7306

Country

United States

Scientific contact point

Organisation

Dyne Therapeutics Inc.

Contact name

Dyne Clinical Trials

Public contact point

Organisation

Dyne Therapeutics Inc.

Contact name

Dyne Clinical Trials

Third parties 21

Locations

7 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 79 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications