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

Phase 1

Recruiting

• Conditions: Myotonic Dystrophy Type 1 (DM1)
• Interventions: Drug: DYNE-101; Drug: Placebo

• Registration Number: NCT05481879
• Lead Sponsor: Dyne Therapeutics

Brief Summary

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 multiple-ascending dose (MAD) Placebo-Controlled Period (24 weeks), a Treatment Period (24 weeks) and a Long-Term Extension (LTE) Period (96 weeks).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-07-28
• Study First Submitted QC: 2022-07-28
• Study First Posted: 2022-08-01
• Study Start: 2022-09-05
• Status Verified: 2024-09
• Last Update Submitted: 2024-10-29
• Last Update Posted: 2024-10-31
• Primary Completion: 2026-07
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 72

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, and 5×STS at screening without the use of assistive devices such as canes, walkers, or orthoses.

Read More

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.

Note: Other inclusion and exclusion criteria may apply.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo-Controlled MAD Period: DYNE-101	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.
Treatment Period: DYNE-101	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.
Treatment Period: DYNE-101	Placebo	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.
Placebo-Controlled MAD Period: Placebo	Placebo	Participants will be randomized to receive DYNE-101 matching placebo, Q4W or Q8W for up to 24 weeks.
Long-Term Extension Period: DYNE-101	DYNE-101	Participants will receive DYNE-101, Q4W or Q8W for up to 96 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Through study completion, up to Week 145

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Splicing Index in Skeletal Muscle Tissue	Baseline up to Week 45
Change From Baseline in Dystrophia Myotonica Protein Kinase (DMPK) Ribonucleic Acid (RNA) Expression in Muscle Tissue	Baseline up to Week 45
Change From Baseline in Hand Grip Relaxation Time	Baseline up to Week 145
Change From Baseline in Myotonia as Measured by Video Hand Opening Time (vHOT)	Baseline up to Week 145
Change From Baseline in Quantitative Myometry Testing (QMT)	Baseline up to Week 145
Change From Baseline in 10-Meter Walk/Run Test (10-MWRT)	Baseline up to Week 145
Change From Baseline in Stair-Ascend/Descend Test	Baseline up to Week 145
Change From Baseline in 5 Times Sit to Stand (5×STS)	Baseline up to Week 145
Change From Baseline in 9-Hole Peg Test (9-HPT)	Baseline up to Week 145
Maximum Observed Plasma Drug Concentration (Cmax) of DYNE-101	Pre-dose, and at multiple timepoints up to Week 145
Time to Maximum Observed Plasma Concentration (tmax) of DYNE-101	Pre-dose, and at multiple timepoints up to Week 145
Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Plasma Concentration (AUCtlast) of DYNE-101	Pre-dose, and at multiple timepoints up to Week 145
Area Under the Concentration-time Curve Extrapolated to Infinity (AUC∞) of DYNE-101 in Plasma	Pre-dose, and at multiple timepoints up to Week 145
Apparent Terminal Elimination Rate Constant (λz) of DYNE-101 in Plasma	Pre-dose, and at multiple timepoints up to Week 145
Apparent Terminal Elimination Half-Life (t½) of DYNE-101 in Plasma	Pre-dose, and at multiple timepoints up to Week 145
Clearance (CL) of DYNE-101 in Plasma	Pre-dose, and at multiple timepoints up to Week 145
Volume of Distribution at Steady State (Vss) of DYNE-101 in Plasma	Pre-dose, and at multiple timepoints up to Week 145
Volume of Distribution at the Terminal Phase (Vz) of DYNE-101 in Plasma	Pre-dose, and at multiple timepoints up to Week 145
Antisense Oligonucleotide (ASO) Concentration of DYNE-101 in Muscle Tissue	Up to Week 45
Percentage of Participants With Antidrug Antibodies (ADAs)	Up to Week 145

Trial Locations

Locations (9)

Centro Clinico Nemo; 🇮🇹 Milan, Italy

Institut de Myologie; 🇫🇷 Paris, France

Ludwig Maximilians University, Munich - Friedrich Baur Institut; 🇩🇪 Munich, Germany

Fondazione Policlinico Universitario A Gemelli-Rome; 🇮🇹 Rome, Italy

Radboud Medical Center; 🇳🇱 Nijmegen, Netherlands

NZCR Auckland; 🇳🇿 Auckland, New Zealand

University College London Hospitals; 🇬🇧 London, United Kingdom

John Walton Muscular Dystrophy Research Centre; 🇬🇧 Newcastle-Upon-Tyne, United Kingdom

Salford Royal Hospital; 🇬🇧 Salford, United Kingdom