- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04743557
Early Phase Human Drug Trial to Investigate DYN101 in Participants 2 to 17 Years With Centronuclear Myopathies (DyNaMic)
July 7, 2022 updated by: Dynacure
A Phase 1/2, Multicenter, Open-label, Dose-confirmation Trial to Evaluate the Safety and Preliminary Efficacy of DYN101 in Participants 2 to 17 Years of Age With Centronuclear Myopathy Caused by Mutations in MTM1 or DNM2
There are no available treatments aside from supportive care for patients with Centronuclear myopathy (CNM).
This trial will assess the safety and tolerability as well as pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of DYN101 in participants 2 to 17 years of age with CNM caused by mutations in DNM2 or MTM1.The trial will consist of a pre-screening consent, a screening period, a run-in period (if applicable), and a Part 1 of 12 weeks with weekly infusion of DYN101 to evaluate safety and tolerability as well as PK, PD and preliminary efficacy.
The dose level may need adjustment based on the Part 1 results of the current study and available data from the Unite-CNM study (DYN101-C101, NCT04033159).
If a dose adjustment is needed, Part 2 will be conducted in the same participants and the newly selected dose level will be used to assess whether efficacy is seen after an additional 12 weeks of treatment.
As this trial is investigational, there is no defined, expected benefit for subjects who participate in this trial except a better knowledge of their disease.
Study Overview
Study Type
Interventional
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
2 years to 17 years (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male or female aged ≥2 to <18 years on the date the main ICF is signed.
- Have a clinically symptomatic CNM, with a documented MTM1 or DNM2 mutation.
Have impaired muscle function as evidenced by:
- MFM20 score between 5% and 80% for subjects ≥2 and <6 years of age, or
- MFM32 score between 5% and 80% for subjects ≥6 years of age.
- Have sufficient skeletal muscle (vastus lateralis, gastrocnemius, or biceps brachii as last resort) to perform 2 open muscle biopsies during the trial, as determined by ultrasound imaging at screening.
- Subject must have platelet count >150,000/µL at screening.
- Parent(s) or legally-authorized representative must be able to provide written, signed and dated informed consent for their child to participate in the trial. Informed assent can be obtained from the child according to local regulations.
- Parent(s) or legally-authorized representative must be at or above the age of legal consent in the jurisdiction of the country in which the trial is taking place.
- Subject, parent(s), and/or legally-authorized representative must have an understanding, ability, and willingness to fully comply with visit frequency, trial procedures, videorecording of assessments where applicable, and restrictions, including contraceptive requirements.
Exclusion Criteria:
- Subject has evidence of clinically significant liver disease.
- Subject has evidence of clinically significant renal disease.
- Presence of significant comorbidities or conditions other than CNM or clinically significant findings during screening of medical history, physical examination, clinical laboratory evaluation, vital signs, or ECG recording for which, in the opinion of the investigator and/or the medical monitor, participation would not be in the best interest of the subject (e.g. compromise the safety or well-being) or that could prevent, limit, or confound the protocol-specified assessments (e.g. taking a muscle biopsy).
- Subject currently enrolled in any interventional trial or scheduled to participate in such a trial whilst participating in the current trial.
- Subject has previously received gene therapy for CNM.
- Subject has severe muscle contractures that would preclude the ability to show improvement in the MFM32 assessment, in the opinion of the investigator.
- Subject has severe airway malacia which could impact the capacity to wean off ventilatory support.
- Subject requires oxygen supplementation.
- For female subjects of childbearing potential: pregnant, breastfeeding, or planning to become pregnant during the trial.
- Current or relevant history of physical or psychiatric illness, and/or any medical disorder that may require treatment or make the subject unlikely to fully complete the trial, or any condition that presents undue risk from the investigational medicinal product (IMP) or procedures.
- Intake of any disallowed therapies by the subject within 12 weeks before the planned first IMP administration.
- Known or suspected intolerance or hypersensitivity to IMP ingredients or closely related compounds.
- Parent(s) or legally authorized representative are legally incapacitated or have limited legal capacity, or have lack of mental capacity to fully understand the protocol requirements and ensure completion of all required trial procedures.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort 1
Weekly infusions of DYN101 at the starting dose level
|
DYN101, is a constrained ethyl gapmer ASO directed against human DNM2 pre-mRNA
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Incidence of drug-related Treatment Emergent Adverse Events (TEAEs)
Time Frame: Baseline until Week 12
|
Baseline until Week 12
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Measurement of DYN101 concentration in plasma
Time Frame: Week 1 Day 1: before the start of infusion (baseline), immediately after the end of infusion, and at 1, 3, 7, 23, 71 hours after the end of infusion. Week 13 Day 1: predose and 3 hours after the end of infusion
|
Week 1 Day 1: before the start of infusion (baseline), immediately after the end of infusion, and at 1, 3, 7, 23, 71 hours after the end of infusion. Week 13 Day 1: predose and 3 hours after the end of infusion
|
Maximum plasma drug concentration (Cmax) for DYN101
Time Frame: Week 1 Day 1: before the start of infusion (baseline), immediately after the end of infusion, and at 1, 3, 7, 23, 71 hours after the end of infusion. Week 13 Day 1: predose and 3 hours after the end of infusion
|
Week 1 Day 1: before the start of infusion (baseline), immediately after the end of infusion, and at 1, 3, 7, 23, 71 hours after the end of infusion. Week 13 Day 1: predose and 3 hours after the end of infusion
|
Area under the Plasma Concentration versus Time Curve (AUC) of DYN101
Time Frame: Week 1 Day 1: before the start of infusion (baseline), immediately after the end of infusion, and at 1, 3, 7, 23, 71 hours after the end of infusion. Week 13 Day 1: predose and 3 hours after the end of infusion
|
Week 1 Day 1: before the start of infusion (baseline), immediately after the end of infusion, and at 1, 3, 7, 23, 71 hours after the end of infusion. Week 13 Day 1: predose and 3 hours after the end of infusion
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
January 1, 2024
Primary Completion (Anticipated)
September 1, 2025
Study Completion (Anticipated)
November 1, 2025
Study Registration Dates
First Submitted
February 3, 2021
First Submitted That Met QC Criteria
February 3, 2021
First Posted (Actual)
February 8, 2021
Study Record Updates
Last Update Posted (Actual)
July 11, 2022
Last Update Submitted That Met QC Criteria
July 7, 2022
Last Verified
July 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- DYN101-C102
- 2020-004608-32 (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
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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