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Centronuclear MyopathyPhase 1/2DyNaMicNCT04743557

Early Phase Human Drug Trial to Investigate DYN101 in Participants 2 to 17 Years With Centronuclear Myopathies

A Phase 1/2 study testing DYN101 in people with Centronuclear Myopathy, run by Dynacure at 2 sites in 2 countries.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 2 to 17 years
Conditions the study is for
Centronuclear Myopathy
What is being tested?
DYN101
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
2 sitesin 2 countries
Study dates
Jan 2024to Nov 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

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 2 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

France1 site

  • I-Motion Institute - Trousseau Hospital

    Paris, 75012

Other trials in France

Germany1 site

  • Universitätsklinikum Essen

    Essen, 45122

Other trials in Germany

About this study

Official title: 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.

Being tested
DYN101
Keywords
Muscular Diseases, Myopathies, Structural, Congenital, Musculoskeletal Diseases, Neuromuscular Diseases, Nervous System Diseases
Medical subject headings
Myopathies, Structural, Congenital, Muscular Diseases, Musculoskeletal Diseases, Neuromuscular Diseases, Nervous System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DYN101Drug

    DYN101, is a constrained ethyl gapmer ASO directed against human DNM2 pre-mRNA

Study groups in NCT04743557
Study groupRoleWhat they receive
Cohort 1ExperimentalWeekly infusions of DYN101 at the starting dose level
Receives: Drug: DYN101

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of drug-related Treatment Emergent Adverse Events (TEAEs)

    Measured: Baseline until Week 12

Secondary outcomes (3)

  1. Measurement of DYN101 concentration in plasma

    Measured: 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

  2. Maximum plasma drug concentration (Cmax) for DYN101

    Measured: 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

  3. Area under the Plasma Concentration versus Time Curve (AUC) of DYN101

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2021
  2. Study startJan 2024 (estimated)
  3. Primary completionSep 2025 (estimated)
  4. Study completionNov 2025 (estimated)

Why it stopped: The first Clinical trial with DYN101 (UNITE-CNM) was early terminated. As a consequence, Dynacure decided to not perform this study.

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04743557
Sponsor's protocol ID
DYN101-C102
Other IDs
2020-004608-32
Acronym
DyNaMic
Status last verified
Jul 2022
First submitted
3 Feb 2021
Last updated
11 Jul 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Tasfaout H, Buono S, Guo S, Kretz C, Messaddeq N, Booten S, Greenlee S, Monia BP, Cowling BS, Laporte J. Antisense oligonucleotide-mediated Dnm2 knockdown prevents and reverts myotubular myopathy in mice. Nat Commun. 2017 Jun 7;8:15661. doi: 10.1038/ncomms15661.

    PubMed 28589938

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing DYN101 in people with Centronuclear Myopathy, run by Dynacure at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 11 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in France, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of drug-related Treatment Emergent Adverse Events (TEAEs) (time frame: Baseline until Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04743557, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2022.

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