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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Myotonic Dystrophy Type 1 (DM1)
• Intervention / Treatment: Drug: DYNE-101; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Dyne Clinical Trials; Phone Number: +1-781-317-1919; Email: clinicaltrials@dyne-tx.com

Study Locations

• France
  • Paris, France, 75013
    • Recruiting
    • Institut de Myologie
    • Contact: Dr. Guillaume Bassez; Phone Number: +33142163791; Email: g.bassez@institut-myologie.org
• Germany
  • Munich, Germany, 80336
    • Recruiting
    • Ludwig Maximilians University, Munich - Friedrich Baur Institut
    • Contact: Marko Mijic; Phone Number: +49 89 440057078; Email: Marko.Mijic@med.uni-muenchen.de
    • Principal Investigator: Benedikt Schoser, MD
    • Contact: Corinna Wirner-Piotrowski; Phone Number: +4989440057071; Email: Corinna.Wirner@med.uni-muenchen.de
• Italy
  • Milan, Italy, 20162
    • Recruiting
    • Centro Clinico NeMO
    • Principal Investigator: Valeria Sansone, MD, PhD
    • Contact: Alessandra DiBari; Phone Number: +393495607450; Email: valeria.sansone@centrocliniconemo.it
  • Rome, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Universitario A Gemelli-Rome
    • Contact: Maria Pirozzoli; Email: mariaceleste.pirozzoli@policlinicogemelli.it
    • Principal Investigator: Marika Pane
• Netherlands
  • Nijmegen, Netherlands
    • Recruiting
    • Radboud Medical Center
    • Contact: Joost Kools, MD; Phone Number: +31 6 44412758; Email: joost.kools@radboudumc.nl
• New Zealand
  • Auckland, New Zealand, 1023
    • Recruiting
    • NZCR Auckland
    • Contact: Olivia Dempster; Phone Number: 7034 +649 373 3474; Email: olivia.dempster@nzcr.co.nz
• United Kingdom
  • London, United Kingdom, NW1 2BU
    • Recruiting
    • University College London Hospitals
    • Contact: Dr. Chris Turner; Phone Number: +44 020 3448 8005; Email: chris.turner7@nhs.net
  • Newcastle-Upon-Tyne, United Kingdom
    • Recruiting
    • John Walton Muscular Dystrophy Research Centre
    • Contact: Jordi Diaz-Manera, MD, PhD; Email: nmd.clinicaltrials@newcastle.ac.uk
  • Salford, United Kingdom, M6 8HD
    • Recruiting
    • Salford Royal Hospital
    • Contact: Kathryn Slevin; Phone Number: +44 0161 206 5203; Email: neuroresearch.nurse@nca.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo-Controlled MAD 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: Placebo-Controlled MAD 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: 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: Long-Term Extension Period: DYNE-101; Participants will receive DYNE-101, Q4W or Q8W for up to 96 weeks.	Drug: DYNE-101; Administered by IV infusion

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Splicing Index in Skeletal Muscle Tissue	Baseline up to Week 97
Change From Baseline in Dystrophia Myotonica Protein Kinase (DMPK) Ribonucleic Acid (RNA) Expression in Muscle Tissue	Baseline up to Week 97
Change From Baseline in Hand Grip Relaxation Time	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 the Terminal Phase (Vz) 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
Antisense Oligonucleotide (ASO) Concentration of DYNE-101 in Muscle Tissue	Up to Week 97
Percentage of Participants With Antidrug Antibodies (ADAs)	Up to Week 145
Change From Baseline in Myotonia as Measured by Video Hand Opening Time (vHOT)	Baseline up to Week 145

Collaborators and Investigators

• Sponsor: Dyne Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: July 28, 2022
• First Submitted That Met QC Criteria: July 28, 2022
• First Posted (Actual): August 1, 2022

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Muscular Disorders, Atrophic; Heredodegenerative Disorders, Nervous System; Muscular Dystrophies; Myotonic Disorders; Myotonic Dystrophy
• Other Study ID Numbers: DYNE101-DM1-201; 2022-000889-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes