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

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ClinicalTrials.gov Identifier: NCT05481879
Recruitment Status : Recruiting
First Posted : August 1, 2022
Last Update Posted : December 22, 2023
Sponsor:
Information provided by (Responsible Party):
Dyne Therapeutics

Study Description
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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).


Condition or disease Intervention/treatment Phase
Myotonic Dystrophy Type 1 (DM1) Drug: DYNE-101 Drug: Placebo Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : September 5, 2022
Estimated Primary Completion Date : July 2026
Estimated Study Completion Date : July 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Through study completion, up to Week 145 ]

Secondary Outcome Measures :
  1. Change From Baseline in Splicing Index in Skeletal Muscle Tissue [ Time Frame: Baseline up to Week 97 ]
  2. Change From Baseline in Dystrophia Myotonica Protein Kinase (DMPK) Ribonucleic Acid (RNA) Expression in Muscle Tissue [ Time Frame: Baseline up to Week 97 ]
  3. Change From Baseline in Hand Grip Relaxation Time [ Time Frame: Baseline up to Week 145 ]
  4. Change From Baseline in Myotonia as Measured by Video Hand Opening Time (vHOT) [ Time Frame: Baseline up to Week 145 ]
  5. Change From Baseline in Quantitative Myometry Testing (QMT) [ Time Frame: Baseline up to Week 145 ]
  6. Change From Baseline in 10-Meter Walk/Run Test (10-MWRT) [ Time Frame: Baseline up to Week 145 ]
  7. Change From Baseline in Stair-Ascend/Descend Test [ Time Frame: Baseline up to Week 145 ]
  8. Change From Baseline in 5 Times Sit to Stand (5×STS) [ Time Frame: Baseline up to Week 145 ]
  9. Change From Baseline in 9-Hole Peg Test (9-HPT) [ Time Frame: Baseline up to Week 145 ]
  10. Maximum Observed Plasma Drug Concentration (Cmax) of DYNE-101 [ Time Frame: Pre-dose, and at multiple timepoints up to Week 145 ]
  11. Time to Maximum Observed Plasma Concentration (tmax) of DYNE-101 [ Time Frame: Pre-dose, and at multiple timepoints up to Week 145 ]
  12. Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Plasma Concentration (AUCtlast) of DYNE-101 [ Time Frame: Pre-dose, and at multiple timepoints up to Week 145 ]
  13. Area Under the Concentration-time Curve Extrapolated to Infinity (AUC∞) of DYNE-101 in Plasma [ Time Frame: Pre-dose, and at multiple timepoints up to Week 145 ]
  14. Apparent Terminal Elimination Rate Constant (λz) of DYNE-101 in Plasma [ Time Frame: Pre-dose, and at multiple timepoints up to Week 145 ]
  15. Apparent Terminal Elimination Half-Life (t½) of DYNE-101 in Plasma [ Time Frame: Pre-dose, and at multiple timepoints up to Week 145 ]
  16. Clearance (CL) of DYNE-101 in Plasma [ Time Frame: Pre-dose, and at multiple timepoints up to Week 145 ]
  17. Volume of Distribution at Steady State (Vss) of DYNE-101 in Plasma [ Time Frame: Pre-dose, and at multiple timepoints up to Week 145 ]
  18. Volume of Distribution at the Terminal Phase (Vz) of DYNE-101 in Plasma [ Time Frame: Pre-dose, and at multiple timepoints up to Week 145 ]
  19. Antisense Oligonucleotide (ASO) Concentration of DYNE-101 in Muscle Tissue [ Time Frame: Up to Week 97 ]
  20. Percentage of Participants With Antidrug Antibodies (ADAs) [ Time Frame: Up to Week 145 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05481879


Contacts
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Contact: Dyne Clinical Trials +1-781-317-1919 clinicaltrials@dyne-tx.com

Locations
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France
Institut de Myologie Recruiting
Paris, France, 75013
Contact: Dr. Guillaume Bassez    +33142163791    g.bassez@institut-myologie.org   
Germany
Ludwig Maximilians University, Munich - Friedrich Baur Institut Recruiting
Munich, Germany, 80336
Contact: Marko Mijic    +49 89 440057078    Marko.Mijic@med.uni-muenchen.de   
Contact: Corinna Wirner-Piotrowski    +4989440057071    Corinna.Wirner@med.uni-muenchen.de   
Principal Investigator: Benedikt Schoser, MD         
Italy
Centro Clinico Nemo Recruiting
Milan, Italy, 20162
Contact: Alessandra DiBari    +393495607450    valeria.sansone@centrocliniconemo.it   
Principal Investigator: Valeria Sansone, MD, PhD         
Fondazione Policlinico Universitario A Gemelli-Rome Recruiting
Rome, Italy, 00168
Contact: Maria Pirozzoli       mariaceleste.pirozzoli@policlinicogemelli.it   
Principal Investigator: Marika Pane         
Netherlands
Radboud Medical Center Recruiting
Nijmegen, Netherlands
Contact: Joost Kools, MD    +31 6 44412758    joost.kools@radboudumc.nl   
New Zealand
NZCR Auckland Recruiting
Auckland, New Zealand, 1023
Contact: Olivia Dempster    +649 373 3474 ext 7034    olivia.dempster@nzcr.co.nz   
United Kingdom
University College London Hospitals Recruiting
London, United Kingdom, NW1 2BU
Contact: Dr. Chris Turner    +44 020 3448 8005    chris.turner7@nhs.net   
John Walton Muscular Dystrophy Research Centre Recruiting
Newcastle-Upon-Tyne, United Kingdom
Contact: Jordi Diaz-Manera, MD, PhD       nmd.clinicaltrials@newcastle.ac.uk   
Salford Royal Hospital Recruiting
Salford, United Kingdom, M6 8HD
Contact: Kathryn Slevin    +44 0161 206 5203    neuroresearch.nurse@nca.nhs.uk   
Sponsors and Collaborators
Dyne Therapeutics
More Information
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Responsible Party: Dyne Therapeutics
ClinicalTrials.gov Identifier: NCT05481879    
Other Study ID Numbers: DYNE101-DM1-201
2022-000889-18 ( EudraCT Number )
First Posted: August 1, 2022    Key Record Dates
Last Update Posted: December 22, 2023
Last Verified: December 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Myotonic Dystrophy
Muscular Dystrophies
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Myotonic Disorders
 Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Genetic Diseases, Inborn