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 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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 116
• 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

• Australia
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Recruiting
      • St. Vincent's Hospital
      • Contact: Alan Lai; Email: alan.lai@svha.org.au
      • Principal Investigator: Dr. Gayatri Jain
• France
  • Nantes, France, 44093
    • Recruiting
    • CHU de Nantes
    • Contact: Marie-Agnès Sourdril; Email: marieagnes.sourdril@chu-nantes.fr
    • Principal Investigator: Yann Péréon, MD, PhD
  • Paris, France, 75013
    • Recruiting
    • Institut de Myologie
    • Contact: Asma Balloumi; Email: a.balloumi@institut-myologie.org
    • Principal Investigator: Dr. Guillaume Bassez
• Germany
  • Berlin, Germany, 10117
    • Recruiting
    • Charité - Universitätsmedizin Berlin
    • Contact: Susanne Behr-Perst; Email: susanne.behr-perst@charite.de
    • Principal Investigator: Elisabetta Gazzerro, MD, PhD
  • Munich, Germany, 80336
    • Recruiting
    • Ludwig Maximilians University, Munich - Friedrich Baur Institut
    • Principal Investigator: Benedikt Schoser, MD
    • Contact: Corinna Wirner-Piotrowski; Email: Corinna.Wirner@med.uni-muenchen.de
    • Sub-Investigator: Stephan Wenninger, MD
• Italy
  • Milan, Italy, 20162
    • Recruiting
    • Centro Clinico NeMO
    • Principal Investigator: Valeria Sansone, MD, PhD
    • Contact: Maribel Evoli; Email: maribel.evoli@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: Eline Sanders; Email: clinicalresearchunit@radboudumc.nl
    • Principal Investigator: Karien Mul
• New Zealand
  • Auckland, New Zealand, 1023
    • Recruiting
    • NZCR Auckland
    • Contact: Miriam Rodrigues; Email: MRodrigues@adhb.govt.nz
    • Principal Investigator: Dr. Richard Roxburgh
• United Kingdom
  • London, United Kingdom, NW1 2BU
    • Recruiting
    • University College London Hospitals
    • Contact: Nikoletta Nikolenko; Email: n.nikolenko@nhs.net
    • Principal Investigator: Dr. Chris Turner
  • Newcastle upon Tyne, United Kingdom
    • Recruiting
    • John Walton Muscular Dystrophy Research Centre
    • Contact: Nicola McLarty; Email: nicola.mclarty1@nhs.net
    • Principal Investigator: Jordi Diaz-Manera
  • Salford, United Kingdom, M6 8HD
    • Recruiting
    • Salford Royal Hospital
    • Contact: Bethan Blackledge; Email: Bethan.blackledge@nca.nhs.uk
    • Principal Investigator: James Lilleker
• United States
  • California
    • Stanford, California, United States, 94305
      • Recruiting
      • Stanford University
      • Contact: Lidia Choniawko; Email: lidiacho@stanford.edu
      • Principal Investigator: Dr. John Day, MD, PhD
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • University of Florida College of Medicine
      • Contact: Debbye Landers; Email: debralanders@peds.ufl.edu
      • Principal Investigator: Dr. Sub Subramony, MD
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University School of Medicine
      • Contact: Patti Hogan, BSN RN, CCRA; Email: hoganpr@iu.edu
      • Principal Investigator: Laurie Gutmann, MD
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Principal Investigator: Andrea Swenson, MD
      • Contact: Heena Olade, RN, MSN; Email: heena-olalde@uiowa.edu
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University in St. Louis
      • Contact: Natalie Goedeker; Email: ngoedeker@wustl.edu
      • Principal Investigator: Dr. Craig Zaidman, MD
  • New York
    • Rochester, New York, United States, 14642
      • Recruiting
      • University of Rochester Medical Center
      • Contact: Jim Hilbert; Email: james_hilbert@urmc.rochester.edu
      • Principal Investigator: Dr. Joahnna Hamel, MD
  • Texas
    • Denton, Texas, United States, 76208
      • Recruiting
      • Neurology Rare Disease Center
      • Principal Investigator: Diana Castro, MD
      • Contact: Isabella Herman; Email: Research@neuromdcenter.com
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University (VCU)
      • Contact: Anarosa Rezeq; Email: anarosa.rezeq@vcuhealth.org
      • Contact: Jodie Howell; Email: jodie.howell@vcuhealth.org
      • Principal Investigator: Nicholas Johnson, M.D., M.Sci., FAAN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult, Older 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 (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 Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: 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: 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: Long-Term Extension Period: DYNE-101; Participants will receive DYNE-101, Q8W for up to 168 weeks.	Drug: DYNE-101; Administered by IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
MAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Through study completion, up to Week 217
Dose Expansion Cohorts: Change From Baseline in Myotonia as Measured by Video Hand Opening Time (vHOT)	Baseline up to Week 25

Secondary Outcome Measures

Outcome Measure	Time Frame
MAD Cohorts: Change From Baseline in Dystrophia Myotonica Protein Kinase (DMPK) Ribonucleic Acid (RNA) Expression in Muscle Tissue	Baseline up to Week 45
MAD Cohorts: Change From Baseline in Hand Grip Relaxation Time	Baseline up to Week 121
MAD Cohorts: Change From Baseline in Quantitative Myometry Testing (QMT)	Baseline up to Week 193
MAD Cohorts: Change From Baseline in 10-Meter Walk/Run Test (10-MWRT)	Baseline up to Week 193
MAD Cohorts: Change From Baseline in Stair-Ascend/Descend Test	Baseline up to Week 121
MAD Cohorts: Change From Baseline in 5 Times Sit to Stand (5×STS)	Baseline up to Week 193
MAD Cohorts: Change From Baseline in 9-Hole Peg Test (9-HPT)	Baseline up to Week 193
MAD Cohorts: Antisense Oligonucleotide (ASO) Concentration of DYNE-101 in Muscle Tissue	Up to Week 45
MAD Cohorts: Change From Baseline in Composite Alternative Splicing Index (CASI) in Skeletal Muscle Tissue	Baseline up to Week 45
MAD Cohorts: Change From Baseline in Myotonia as Measured by vHOT	Baseline up to Week 193
MAD Cohorts: Maximum Observed Plasma Drug Concentration (Cmax) of DYNE-101	Pre-dose, and at multiple timepoints up to Week 217
MAD Cohorts: Time to Maximum Observed Plasma Concentration (tmax) of DYNE-101	Pre-dose, and at multiple timepoints up to Week 217
MAD Cohorts: 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 217
MAD Cohorts: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC∞) of DYNE-101 in Plasma	Pre-dose, and at multiple timepoints up to Week 217
MAD Cohorts: Apparent Terminal Elimination Rate Constant (λz) of DYNE-101 in Plasma	Pre-dose, and at multiple timepoints up to Week 217
MAD Cohorts: Apparent Terminal Elimination Half-Life (t1/2) of DYNE-101 in Plasma	Pre-dose, and at multiple timepoints up to Week 217
MAD Cohorts: Clearance (CL) of DYNE-101 in Plasma	Pre-dose, and at multiple timepoints up to Week 217
MAD Cohorts: Volume of Distribution at the Terminal Phase (Vz) of DYNE-101 in Plasma	Pre-dose, and at multiple timepoints up to Week 217
MAD Cohorts: Volume of Distribution at Steady State (Vss) of DYNE-101 in Plasma	Pre-dose, and at multiple timepoints up to Week 217
MAD Cohorts: Number of Participants With Antidrug Antibodies (ADAs)	Up to Week 217
Dose Expansion Cohorts: Change From Baseline in CASI in Skeletal Muscle Tissue	Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in QMT Total	Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in 10-MWRT	Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in 5×STS	Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in 9-HPT	Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in Myotonic Dystrophy Health Index (MDHI) Total Score	Baseline up to Week 25
Dose Expansion Cohorts: Patient Global Impression of Change (PGI-C)	Baseline up to Week 25
Clinician Global Impression of Change (CGI-C)	Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in Patient Global Impression of Severity (PGI-S)	Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in Clinician Global Impression of Severity (CGI-S)	Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in MDHI Subscale Scores	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	Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in Percent Predicted Hand Grip Strength	Baseline up to Week 25

Collaborators and Investigators

• Sponsor: Dyne Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2022
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029

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): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Muscular Disorders, Atrophic; Muscular Dystrophies; Myotonic Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myotonic Dystrophy
• Other Study ID Numbers: DYNE101-DM1-201; 2023-510353-42-00 (Ctis)

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