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

Purpose

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.

Condition

  • Myotonic Dystrophy Type 1 (DM1)

Eligibility

Eligible Ages
Between 18 Years and 65 Years
Eligible Sex
All
Accepts 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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
MAD Cohort: Placebo-Controlled Period: DYNE-101 		Participants will be randomized to receive ascending doses of DYNE-101, once every 4 weeks (Q4W) or once every 8 weeks (Q8W) for up to 24 weeks.
  • Drug: DYNE-101
    Administered by IV infusion
Placebo Comparator
MAD Cohort: Placebo-Controlled Period: Placebo 		Participants will be randomized to receive DYNE-101 matching placebo, Q4W or Q8W for up to 24 weeks.
  • Drug: Placebo
    Administered by IV infusion
Experimental
MAD Cohort: Treatment Period: DYNE-101 		Participants who receive DYNE-101 in Placebo-Controlled Period will continue to receive DYNE-101, Q4W or Q8W for up to 24 weeks. Participants who receive placebo in Placebo-Controlled Period will receive DYNE-101, Q4W or Q8W for up to 24 weeks.
  • Drug: DYNE-101
    Administered by IV infusion
  • Drug: Placebo
    Administered by IV infusion
Experimental
MAD Cohort: Long-Term Extension Period: DYNE-101 		Participants will receive DYNE-101, Q4W or Q8W for up to 168 weeks.
  • Drug: DYNE-101
    Administered by IV infusion
Experimental
Dose Expansion Cohort: Placebo-Controlled Period: DYNE-101 		Participants will receive DYNE-101, Q8W for up to 24 weeks.
  • Drug: DYNE-101
    Administered by IV infusion
Experimental
Dose Expansion Cohort: Placebo-Controlled Period: Placebo 		Participants will receive DYNE-101 matching placebo, Q8W for up to 24 weeks.
  • Drug: Placebo
    Administered by IV infusion
Experimental
Dose Expansion Cohort: Treatment Period: DYNE-101 		Participants who receive DYNE-101 in Placebo-Controlled Period will continue to receive DYNE-101, Q8W for up to 24 weeks. Participants who receive placebo in Placebo-Controlled Period will receive DYNE-101, Q8W for up to 24 weeks.
  • Drug: DYNE-101
    Administered by IV infusion
  • Drug: Placebo
    Administered by IV infusion
Experimental
Dose Expansion Cohort: Long-Term Extension Period: DYNE-101 		Participants will receive DYNE-101, Q8W for up to 168 weeks.
  • Drug: DYNE-101
    Administered by IV infusion

Recruiting Locations

Washington University in St. Louis and nearby locations

Washington University in St. Louis
St Louis, Missouri 63110
Contact:
Natalie Goedeker
ngoedeker@wustl.edu

More Details

NCT ID
NCT05481879
Status
Recruiting
Sponsor
Dyne Therapeutics

Study Contact

Dyne Clinical Trials
+1-781-317-1919
clinicaltrials@dyne-tx.com