HUMANISED IGG1 KAPPA FRAGMENT ANTIBODY TARGETING TFR1 CONJUGATED TO P125 OLIGONUCLEOTIDE for Myotonic dystrophy type 1

Inclusion criteria

• {"criterion_text":"- 1. Age 16 to ≤ 65 years at the time of signing the informed consent/assent form\n- 8. If being treated with testosterone, on a stable replacement dose for 30 days prior to screening\n- 9. Participants must agree to follow protocol-specified highly effective contraception guidance as described in the protocol\n- 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\n- 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\n- 2. Diagnosis of DM1 confirmed by molecular genetics with trinucleotide repeat size > 100. Historical results from clinical testing are acceptable\n- 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\n- 4. Hand grip strength averaged from both sides ≥ 15% and ≤ 85% predicted of normal\n- 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.\n- 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\n- 7. Body mass index (BMI) < 35kg/m2"}

Exclusion criteria

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

Primary endpoints

• {"endpoint_text":"- 5×STS time, change from baseline at Week 49","definition_or_measurement_approach":"Change from baseline at Week 49 measured using the 5×STS (five-times sit-to-stand) test time."}

Secondary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Change from baseline at Week 49 measured for the listed clinical and patient-reported outcomes (vHOT middle finger, QMT total, CGI-C, 10-MWRT velocity, PGI-C, DM1-ACTIVC total score, MDHI total and subscales, PGI-S, CGI-S, 9-HPT) as specified in protocol."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Standard plasma PK parameters: Cmax, tmax, AUC0-tlast, AUC∞, λZ, t½, CL, Vz, Vss measured from plasma concentration-time samples per PK schedule in protocol."}
• {"endpoint_text":"- Incidence of anti-drug antibodies (ADAs)","definition_or_measurement_approach":"Incidence of treatment-emergent anti-drug antibodies measured by validated immunogenicity assays per protocol schedule."}
• {"endpoint_text":"- * 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","definition_or_measurement_approach":"Safety endpoints assessed by recording TEAEs/SAEs, relatedness, discontinuations, vital signs, 12-lead ECGs, clinical laboratory values, and C-SSRS results per safety monitoring schedule."}

Belgium

Earliest CTIS Part Ii Submission Date

31-03-2026

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

28

Number Of Sites

2

Number Of Participants

6

France

Earliest CTIS Part Ii Submission Date

31-03-2026

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

28

Number Of Sites

5

Number Of Participants

15

Italy

Earliest CTIS Part Ii Submission Date

19-01-2026

Latest Decision Or Authorization Date

30-04-2026

Processing Time Days

101

Number Of Sites

5

Number Of Participants

15

Spain

Earliest CTIS Part Ii Submission Date

02-04-2026

Latest Decision Or Authorization Date

30-04-2026

Processing Time Days

28

Number Of Sites

2

Number Of Participants

6

Netherlands

Earliest CTIS Part Ii Submission Date

21-04-2026

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

7

Number Of Sites

2

Number Of Participants

6

Denmark

Earliest CTIS Part Ii Submission Date

31-03-2026

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

28

Number Of Sites

2

Number Of Participants

6

Germany

Earliest CTIS Part Ii Submission Date

16-04-2026

Latest Decision Or Authorization Date

29-04-2026

Processing Time Days

13

Number Of Sites

4

Number Of Participants

18

Primary sponsor

Full Name

Dyne Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Iqvia Laboratories Limited

Name

PPD Development LP

Responsibilities

Biomarkers and PK

Name

Pharmaceutical Product Development LLC

Responsibilities

consumables & equipment, packaging & labelling, PT Card, CT hotline, clinical endpoint committee

Name

Suvoda LLC

Name

Longboat Clinical Limited

Responsibilities

site document repository

Name

Medidata Solutions Inc.

Third parties

• {"country":"Germany","full_name":"Centogene GmbH","duties_or_roles":"genetic testing","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Trinds LLC","duties_or_roles":"PT Training, vHOT reviewers and MPT Management​","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Chillibean Limited","duties_or_roles":"ideo file storage functional assessments​","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Iqvia Laboratories Limited","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"eResearchTechnology GmbH","duties_or_roles":"Cardiac / respiratory testing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Quest Diagnostics Nichols Institute Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Quanterix Corp.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Australia","full_name":"Cogstate Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Meeting Protocol Worldwide LP","duties_or_roles":"Investigator Meeting Planning","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Association Institut De Myologie","duties_or_roles":"QMT / MyoTools","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Actigraph LLC","duties_or_roles":"wearable devices","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"PPD Development LP","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Pharmaceutical Product Development LLC","duties_or_roles":"consumables & equipment, packaging & labelling, PT Card, CT hotline, clinical endpoint committee","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Evidera Inc.","duties_or_roles":"Exit Interviews","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Longboat Clinical Limited","duties_or_roles":"site document repository","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Charles River Laboratories Inc.","duties_or_roles":"Immunogenicity/ADA​","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP (US address)","duties_or_roles":"Biomarkers and PK","organisation_type":"Pharmaceutical company"}