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

Phase 2Active Not RecruitingNCT05481879

Dyne Therapeutics127 enrolled

Overview

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 (208 weeks) in both multiple-ascending dose (MAD) and dose expansion cohorts.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

127

Conditions

Myotonic Dystrophy Type 1 (DM1)

Interventions

DYNE-101DRUG

Administered by IV infusion

PlaceboDRUG

Administered by IV infusion

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (20)

Stanford University

Stanford, California, United States

University of Florida College of Medicine

Gainesville, Florida, United States

Outcomes

Primary Outcomes

MAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Time frame: Through study completion, up to Week 257

Dose Expansion Cohorts: Change From Baseline in Myotonia as Measured by Video Hand Opening Time (vHOT)

Time frame: Baseline up to Week 25

Secondary Outcomes

MAD Cohorts: Change From Baseline in Composite Alternative Splicing Index (CASI) in Skeletal Muscle Tissue

Time frame: Baseline up to Week 45

MAD Cohorts: Change From Baseline in Dystrophia Myotonica Protein Kinase (DMPK) Ribonucleic Acid (RNA) Expression in Muscle Tissue

Time frame: Baseline up to Week 45

MAD Cohorts: Change From Baseline in Hand Grip Relaxation Time

Time frame: Baseline up to Week 121

MAD Cohorts: Change From Baseline in Myotonia as Measured by vHOT

Time frame: Baseline up to Week 257

MAD Cohorts: Change From Baseline in Quantitative Myometry Testing (QMT)

Time frame: Baseline up to Week 257

MAD Cohorts: Change From Baseline in 10-Meter Walk/Run Test (10-MWRT)

Time frame: Baseline up to Week 257

MAD Cohorts: Change From Baseline in Stair-Ascend/Descend Test

Time frame: Baseline up to Week 121

MAD Cohorts: Change From Baseline in 5 Times Sit to Stand (5×STS)

Data from ClinicalTrials.gov

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Indiana University School of Medicine

Indianapolis, Indiana, United States

University of Iowa

Iowa City, Iowa, United States

Washington University in St. Louis

St Louis, Missouri, United States

University of Rochester Medical Center

Rochester, New York, United States

Neurology Rare Disease Center

Denton, Texas, United States

Virginia Commonwealth University (VCU)

Richmond, Virginia, United States

St. Vincent's Hospital

Fitzroy, Victoria, Australia

CHU de Nantes

Nantes, France

...and 10 more locations

Time frame: Baseline up to Week 257

MAD Cohorts: Change From Baseline in 9-Hole Peg Test (9-HPT)

Time frame: Baseline up to Week 257

MAD Cohorts: Maximum Observed Plasma Drug Concentration (Cmax) of DYNE-101

Time frame: Pre-dose, and at multiple timepoints up to Week 257

MAD Cohorts: Time to Maximum Observed Plasma Concentration (tmax) of DYNE-101

Time frame: Pre-dose, and at multiple timepoints up to Week 257

MAD Cohorts: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Plasma Concentration (AUCtlast) of DYNE-101

Time frame: Pre-dose, and at multiple timepoints up to Week 257

MAD Cohorts: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC∞) of DYNE-101 in Plasma

Time frame: Pre-dose, and at multiple timepoints up to Week 257

MAD Cohorts: Apparent Terminal Elimination Rate Constant (λz) of DYNE-101 in Plasma

Time frame: Pre-dose, and at multiple timepoints up to Week 257

MAD Cohorts: Apparent Terminal Elimination Half-Life (t1/2) of DYNE-101 in Plasma

Time frame: Pre-dose, and at multiple timepoints up to Week 257

MAD Cohorts: Clearance (CL) of DYNE-101 in Plasma

Time frame: Pre-dose, and at multiple timepoints up to Week 257

MAD Cohorts: Volume of Distribution at the Terminal Phase (Vz) of DYNE-101 in Plasma

Time frame: Pre-dose, and at multiple timepoints up to Week 257

MAD Cohorts: Volume of Distribution at Steady State (Vss) of DYNE-101 in Plasma

Time frame: Pre-dose, and at multiple timepoints up to Week 257

MAD Cohorts: Antisense Oligonucleotide (ASO) Concentration of DYNE-101 in Muscle Tissue

Time frame: Up to Week 45

MAD Cohorts: Number of Participants With Antidrug Antibodies (ADAs)

Time frame: Up to Week 257

Dose Expansion Cohorts: Change From Baseline in CASI in Skeletal Muscle Tissue

Time frame: Baseline up to Week 25

Dose Expansion Cohorts: Change From Baseline in QMT Total

Time frame: Baseline up to Week 25

Dose Expansion Cohorts: Change From Baseline in 10-MWRT

Time frame: Baseline up to Week 25

Dose Expansion Cohorts: Change From Baseline in 5×STS

Time frame: Baseline up to Week 25

Dose Expansion Cohorts: Change From Baseline in 9-HPT

Time frame: Baseline up to Week 25

Dose Expansion Cohorts: Change From Baseline in Myotonic Dystrophy Health Index (MDHI) Total Score

Time frame: Baseline up to Week 25

Dose Expansion Cohorts: Patient Global Impression of Change (PGI-C)

Time frame: Baseline up to Week 25

Clinician Global Impression of Change (CGI-C)

Time frame: Baseline up to Week 25

Dose Expansion Cohorts: Change From Baseline in Patient Global Impression of Severity (PGI-S)

Time frame: Baseline up to Week 25

Dose Expansion Cohorts: Change From Baseline in Clinician Global Impression of Severity (CGI-S)

Time frame: Baseline up to Week 25

Dose Expansion Cohorts: Change From Baseline in MDHI Subscale Scores

Time frame: Baseline up to Week 25

Dose Expansion Cohorts: Change From Baseline at in Myotonic Dystrophy type 1 Activity and Participation Scale (DM1-ACTIV^C) Total Score

Time frame: Baseline up to Week 25

Dose Expansion Cohorts: Change From Baseline in Percent Predicted Hand Grip Strength

Time frame: Baseline up to Week 25