Myotonic Dystrophy Type 1 (DM1)Phase 1/2ACHIEVENCT05481879
Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-101 in Participants With Myotonic Dystrophy Type 1
A Phase 1/2 study testing DYNE-101 in people with Myotonic Dystrophy Type 1 (DM1), run by Dyne Therapeutics at 20 sites in 8 countries.
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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Myotonic Dystrophy Type 1 (DM1)
- What is being tested?
- DYNE-101
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 127 participants
- Where
- 20 sitesin 8 countries
- Study dates
- 5 Sep 2022to Jul 2029
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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%.
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- 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.
Trial locations and contacts
20 sites in 8 countries.
20 sites in 8 countries
United States8 sites
Neurology Rare Disease Center
Denton, Texas, 76208
University of Florida College of Medicine
Gainesville, Florida, 32610
Indiana University School of Medicine
Indianapolis, Indiana, 46202
University of Iowa
Iowa City, Iowa, 52242
Virginia Commonwealth University (VCU)
Richmond, Virginia, 23298
University of Rochester Medical Center
Rochester, New York, 14642
Washington University in St. Louis
St Louis, Missouri, 63110
Stanford University
Stanford, California, 94305
United Kingdom3 sites
University College London Hospitals
London, NW1 2BU
John Walton Muscular Dystrophy Research Centre
Newcastle upon Tyne
Salford Royal Hospital
Salford, M6 8HD
Germany2 sites
Charité - Universitätsmedizin Berlin
Berlin, 10117
Ludwig Maximilians University, Munich - Friedrich Baur Institut
Munich, 80336
Italy2 sites
Centro Clinico Nemo
Milan, 20162
Fondazione Policlinico Universitario A Gemelli-Rome
Rome, 00168
About this study
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
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.
- Conditions
- Myotonic Dystrophy Type 1 (DM1)
- Being tested
- DYNE-101, Placebo
- Medical subject headings
- Myotonic Dystrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DYNE-101Drug
Administered by IV infusion
PlaceboDrug
Administered by IV infusion
| Study group | Role | What they receive |
|---|---|---|
| MAD Cohort: Placebo-Controlled Period: DYNE-101 | Experimental | 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. Receives: Drug: DYNE-101 |
| MAD Cohort: Placebo-Controlled Period: Placebo | Placebo comparator | Participants will be randomized to receive DYNE-101 matching placebo, Q4W or Q8W for up to 24 weeks. Receives: Drug: Placebo |
| MAD Cohort: Treatment Period: DYNE-101 | Experimental | 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. Receives: Drug: DYNE-101; Drug: Placebo |
| MAD Cohort: Long-Term Extension Period: DYNE-101 | Experimental | Participants will receive DYNE-101, Q4W or Q8W for up to 208 weeks. Receives: Drug: DYNE-101 |
| Dose Expansion Cohort: Placebo-Controlled Period: DYNE-101 | Experimental | Participants will receive DYNE-101, Q8W for up to 24 weeks. Receives: Drug: DYNE-101 |
| Dose Expansion Cohort: Placebo-Controlled Period: Placebo | Experimental | Participants will receive DYNE-101 matching placebo, Q8W for up to 24 weeks. Receives: Drug: Placebo |
| Dose Expansion Cohort: Treatment Period: DYNE-101 | Experimental | 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. Receives: Drug: DYNE-101; Drug: Placebo |
| Dose Expansion Cohort: Long-Term Extension Period: DYNE-101 | Experimental | Participants will receive DYNE-101, Q8W for up to 208 weeks. Receives: Drug: DYNE-101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
MAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Measured: Through study completion, up to Week 257
Dose Expansion Cohorts: Change From Baseline in Myotonia as Measured by Video Hand Opening Time (vHOT)
Measured: Baseline up to Week 25
Secondary outcomes (33)
MAD Cohorts: Change From Baseline in Composite Alternative Splicing Index (CASI) in Skeletal Muscle Tissue
Measured: Baseline up to Week 45
MAD Cohorts: Change From Baseline in Dystrophia Myotonica Protein Kinase (DMPK) Ribonucleic Acid (RNA) Expression in Muscle Tissue
Measured: Baseline up to Week 45
MAD Cohorts: Change From Baseline in Hand Grip Relaxation Time
Measured: Baseline up to Week 121
MAD Cohorts: Change From Baseline in Myotonia as Measured by vHOT
Measured: Baseline up to Week 257
MAD Cohorts: Change From Baseline in Quantitative Myometry Testing (QMT)
Measured: Baseline up to Week 257
MAD Cohorts: Change From Baseline in 10-Meter Walk/Run Test (10-MWRT)
Measured: Baseline up to Week 257
MAD Cohorts: Change From Baseline in Stair-Ascend/Descend Test
Measured: Baseline up to Week 121
MAD Cohorts: Change From Baseline in 5 Times Sit to Stand (5×STS)
Measured: Baseline up to Week 257
MAD Cohorts: Change From Baseline in 9-Hole Peg Test (9-HPT)
Measured: Baseline up to Week 257
MAD Cohorts: Maximum Observed Plasma Drug Concentration (Cmax) of DYNE-101
Measured: Pre-dose, and at multiple timepoints up to Week 257
MAD Cohorts: Time to Maximum Observed Plasma Concentration (tmax) of DYNE-101
Measured: 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
Measured: 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
Measured: Pre-dose, and at multiple timepoints up to Week 257
MAD Cohorts: Apparent Terminal Elimination Rate Constant (λz) of DYNE-101 in Plasma
Measured: Pre-dose, and at multiple timepoints up to Week 257
MAD Cohorts: Apparent Terminal Elimination Half-Life (t1/2) of DYNE-101 in Plasma
Measured: Pre-dose, and at multiple timepoints up to Week 257
MAD Cohorts: Clearance (CL) of DYNE-101 in Plasma
Measured: 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
Measured: Pre-dose, and at multiple timepoints up to Week 257
MAD Cohorts: Volume of Distribution at Steady State (Vss) of DYNE-101 in Plasma
Measured: Pre-dose, and at multiple timepoints up to Week 257
MAD Cohorts: Antisense Oligonucleotide (ASO) Concentration of DYNE-101 in Muscle Tissue
Measured: Up to Week 45
MAD Cohorts: Number of Participants With Antidrug Antibodies (ADAs)
Measured: Up to Week 257
Dose Expansion Cohorts: Change From Baseline in CASI in Skeletal Muscle Tissue
Measured: Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in QMT Total
Measured: Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in 10-MWRT
Measured: Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in 5×STS
Measured: Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in 9-HPT
Measured: Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in Myotonic Dystrophy Health Index (MDHI) Total Score
Measured: Baseline up to Week 25
Dose Expansion Cohorts: Patient Global Impression of Change (PGI-C)
Measured: Baseline up to Week 25
Clinician Global Impression of Change (CGI-C)
Measured: Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in Patient Global Impression of Severity (PGI-S)
Measured: Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in Clinician Global Impression of Severity (CGI-S)
Measured: Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in MDHI Subscale Scores
Measured: 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
Measured: Baseline up to Week 25
Dose Expansion Cohorts: Change From Baseline in Percent Predicted Hand Grip Strength
Measured: Baseline up to Week 25
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2022
- Study start5 Sep 2022
- Primary completionJul 2029 (estimated)
- Study completionJul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myotonic Dystrophy Type 1 (DM1)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dyne Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05481879
- Sponsor's protocol ID
- DYNE101-DM1-201
- Other IDs
- 2023-510353-42-00, 2023
- Acronym
- ACHIEVE
- Status last verified
- Sep 2026
- First submitted
- 28 Jul 2022
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No