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

Myotonic Dystrophy Type 1 (DM1) Clinical Trial

— ACHIEVE  

Official title:

A Randomized, Placebo-Controlled, Multiple Ascending Dose Study Assessing Safety, Tolerability, Pharmacodynamics, Efficacy, and Pharmacokinetics of DYNE-101 Administered to Participants With Myotonic Dystrophy Type 1

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05481879
• Other study ID #: DYNE101-DM1-201
• Secondary ID: 2022-000889-18
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 5, 2022
• Est. completion date: July 2026

Study information

• Verified date: December 2023
• Source: Dyne Therapeutics
• Contact: Dyne Clinical Trials
• Phone: +1-781-317-1919
• Email: clinicaltrials[@]dyne-tx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: July 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 49 Years

Eligibility

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.

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.

Related Conditions & MeSH terms

• Myotonic Dystrophy
• Myotonic Dystrophy Type 1 (DM1)

Intervention

Drug:
• DYNE-101
Administered by IV infusion
• Placebo
Administered by IV infusion

Locations

Country	Name	City	State
France	Institut de Myologie	Paris
Germany	Ludwig Maximilians University, Munich - Friedrich Baur Institut	Munich
Italy	Centro Clinico Nemo	Milan
Italy	Fondazione Policlinico Universitario A Gemelli-Rome	Rome
Netherlands	Radboud Medical Center	Nijmegen
New Zealand	NZCR Auckland	Auckland
United Kingdom	University College London Hospitals	London
United Kingdom	John Walton Muscular Dystrophy Research Centre	Newcastle-Upon-Tyne
United Kingdom	Salford Royal Hospital	Salford

Sponsors (1)

Lead Sponsor	Collaborator
Dyne Therapeutics

Countries where clinical trial is conducted

France,  Germany,  Italy,  Netherlands,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)		Through study completion, up to Week 145
Secondary	Change From Baseline in Splicing Index in Skeletal Muscle Tissue		Baseline up to Week 97
Secondary	Change From Baseline in Dystrophia Myotonica Protein Kinase (DMPK) Ribonucleic Acid (RNA) Expression in Muscle Tissue		Baseline up to Week 97
Secondary	Change From Baseline in Hand Grip Relaxation Time		Baseline up to Week 145
Secondary	Change From Baseline in Myotonia as Measured by Video Hand Opening Time (vHOT)		Baseline up to Week 145
Secondary	Change From Baseline in Quantitative Myometry Testing (QMT)		Baseline up to Week 145
Secondary	Change From Baseline in 10-Meter Walk/Run Test (10-MWRT)		Baseline up to Week 145
Secondary	Change From Baseline in Stair-Ascend/Descend Test		Baseline up to Week 145
Secondary	Change From Baseline in 5 Times Sit to Stand (5×STS)		Baseline up to Week 145
Secondary	Change From Baseline in 9-Hole Peg Test (9-HPT)		Baseline up to Week 145
Secondary	Maximum Observed Plasma Drug Concentration (Cmax) of DYNE-101		Pre-dose, and at multiple timepoints up to Week 145
Secondary	Time to Maximum Observed Plasma Concentration (tmax) of DYNE-101		Pre-dose, and at multiple timepoints up to Week 145
Secondary	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
Secondary	Area Under the Concentration-time Curve Extrapolated to Infinity (AUC8) of DYNE-101 in Plasma		Pre-dose, and at multiple timepoints up to Week 145
Secondary	Apparent Terminal Elimination Rate Constant (?z) of DYNE-101 in Plasma		Pre-dose, and at multiple timepoints up to Week 145
Secondary	Apparent Terminal Elimination Half-Life (t½) of DYNE-101 in Plasma		Pre-dose, and at multiple timepoints up to Week 145
Secondary	Clearance (CL) of DYNE-101 in Plasma		Pre-dose, and at multiple timepoints up to Week 145
Secondary	Volume of Distribution at Steady State (Vss) of DYNE-101 in Plasma		Pre-dose, and at multiple timepoints up to Week 145
Secondary	Volume of Distribution at the Terminal Phase (Vz) of DYNE-101 in Plasma		Pre-dose, and at multiple timepoints up to Week 145
Secondary	Antisense Oligonucleotide (ASO) Concentration of DYNE-101 in Muscle Tissue		Up to Week 97
Secondary	Percentage of Participants With Antidrug Antibodies (ADAs)		Up to Week 145