Early Phase Human Drug Trial to Investigate Dynamin 101 (DYN101) in Patients ≥ 16 Years With Centronuclear Myopathies (Unite-CNM)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT04033159 |
Recruitment Status :
Recruiting
First Posted : July 25, 2019
Last Update Posted : September 30, 2020
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
There are no available treatments aside from supportive care for patients with Centronuclear myopathy (CNM). This trial will assess the safety, tolerability, PK and PD/preliminary efficacy of a new medicine called DYN101 in patients ≥ 16 years of age with CNM caused by mutations in DNM2 or MTM1.
The trial will consist of a consent, a screening period, a run-in period (if applicable), a Single dose treatment part (SAD) with 4 weeks of follow-up after the drug administration and a washout period of at least 12 weeks (followed by follow-up phone calls), a Multiple dose treatment part (MAD) of 12 weeks of weekly dosing, and a Multiple dose extension part of 12 weeks. All subjects will participate in the SAD, MAD, and MAD extension parts, unless they withdraw. During this time, multiple test will be performed in order to better understand how the drug is distributed and then later removed from the body and whether there any signs of an effect.
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.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Centronuclear Myopathy | Drug: DYN101 | Phase 1 Phase 2 |
There are no available treatments aside from supportive care for patients with Centronuclear myopathy (CNM). This trial will assess the safety, tolerability, PK and PD/preliminary efficacy of DYN101 in patients ≥ 16 years of age with CNM caused by mutations in DNM2 or MTM1.
DYN101 is a synthetically manufactured constrained ethyl gapmer ASO directed against DNM2 pre-mRNA. DYN101 will be provided as a sterile concentrated solution for reconstitution into an infusion solution for intravenous (IV) administration, and will be diluted into a 0.9% sodium chloride solution before administration.
The trial will consist of a pre-screening consent, a screening period, a run-in period (if applicable), a SAD part with 4 weeks of follow-up after IMP administration and a washout period of at least 12 weeks (followed by follow-up phone calls until the MAD part starts), a MAD part of 12 weeks, and a MAD extension part of 12 weeks. All subjects will participate in the SAD, MAD, and MAD extension parts, unless they withdraw. End-of-treatment assessments will be performed after 24 weeks of MAD treatment have been completed, i.e. at the Week 25 visit. Subjects will be followed up on adverse events (AEs) and concomitant medications 3 months after the last IMP administration.
The primary analysis will be performed when all subjects in all cohorts have completed 12 weeks of MAD treatment or discontinued earlier. The final analysis will be performed when all subjects have completed 24 weeks of MAD treatment (12 weeks in the MAD part + 12 weeks in the MAD extension part; Week 25 visit) or discontinued earlier.
As this trial is investigational, there is no defined, expected benefit for subjects who participate in this trial except a better knowledge of their pathology, and the knowledge that they contribute to RNA-targeted therapy for CNM patients carrying MTM1 and DNM2 mutations.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 18 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Intervention Model Description: | Trial consisting of pre-screening consent, screening period, run-in period (if applicable), SAD part with 4 weeks follow-up after IMP and washout period of ≥ 12 weeks, MAD part of 12 weeks and MAD extension part of 12 weeks. All subjects to participate in SAD, MAD, and MAD extension unless they withdraw. Subjects to receive DYN101 in a low (1.5 mg/kg), middle (4.5 mg/kg) or high (9 mg/kg) dose in Cohorts 1, 2 and 3 respectively, and remain on assigned dose throughout the trial (unless IDMC advises otherwise). Each cohort will have 3 subjects with a DNM2 mutation and 3 subjects with a MTM1 mutation. Cohorts will enroll in a sequential staggered approach with an interval of ≥7 days between dosing of the first and the next subject in a cohort (after Medical Monitor 48hr safety data review). |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1/2 Trial on the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Exploratory Efficacy of DYN101 in Patients ≥ 16 Years of Age With Centronuclear Myopathies Caused by Mutations in DNM2 or MTM1. |
Actual Study Start Date : | January 9, 2020 |
Estimated Primary Completion Date : | April 2022 |
Estimated Study Completion Date : | April 2022 |

Arm | Intervention/treatment |
---|---|
Experimental: cohort 1
DYN101 in a low dose (1.5 mg/kg), (unless the IDMC advises otherwise). In each cohort, there will be 3 subjects with a mutation in DNM2 (subcohort a) and 3 subjects with a mutation in MTM1 (subcohort b).
|
Drug: DYN101
DYN101, is a constrained ethyl gapmer ASO directed against human DNM2 RNA
Other Name: there is no other intervention name |
Experimental: cohort 2
DYN101 in a middle dose (4.5 mg/kg), (unless the IDMC advises otherwise). In each cohort, there will be 3 subjects with a mutation in DNM2 (subcohort a) and 3 subjects with a mutation in MTM1 (subcohort b).
|
Drug: DYN101
DYN101, is a constrained ethyl gapmer ASO directed against human DNM2 RNA
Other Name: there is no other intervention name |
Experimental: cohort 3
DYN101 in a high dose (9 mg/kg), (unless the IDMC advises otherwise). In each cohort, there will be 3 subjects with a mutation in DNM2 (subcohort a) and 3 subjects with a mutation in MTM1 (subcohort b).
|
Drug: DYN101
DYN101, is a constrained ethyl gapmer ASO directed against human DNM2 RNA
Other Name: there is no other intervention name |
- incidence of drug-related Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Baseline until Week 25 ]Incidence of drug-related, treatment-emergent AEs during the study period (through to Week 25).

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 16 Years and older (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion criteria:
- Male or female aged ≥ 16 years on the date of signing the main Informed Consent Form (ICF).
- Have a documented mutation in DNM2 or MTM1.
-
Meet the following criteria at screening:
- Platelet count > 150,000/µL,
- Normal kidney function, as supported by values of blood urea nitrogen (BUN), creatinine, cystatin C, and estimated Glomerular Filtration Rate (eGFR); all abnormal results of these tests should have a medically plausible reason and should be discussed with the medical monitor before the subject may be screened and/or dosed for the study.
- Normal liver function, as supported by values of Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyltransferase (GGT), and bilirubin not higher than 1.5 times the upper limit of normal. There should be a medically plausible reason for the elevation of these parameters outside of the normal range, and a discussion with the medical monitor should occur in this situation before the subject may be screened and/or dosed for the study.
Note: Retesting of subjects should always be discussed with the sponsor and/or medical monitor. Retesting of laboratory values that lead to exclusion will be allowed once using an unscheduled visit during the screening period to assess eligibility. This visit should be at least 2 weeks later than the original screening visit.
- Have a symptomatic CNM in the opinion of the investigator, at least mild to moderately affected, i.e. showing clinical symptoms in at least 2 of the domains that will be investigated in this trial (respiratory, muscle strength and function, dysphagia), and be ambulatory, i.e. being able to walk 10 steps, if needed with support/assisted. If a subject is non-ambulatory but highly functioning in the view of the investigator, he/she may be included following discussion with the sponsor.
- Have an understanding, ability, and willingness to fully comply with visit frequency, trial procedures and restrictions, including contraceptive requirements.
- Able to provide written, signed and dated informed consent/assent to participate in the trial. Parental consent (one or both parents) and an assent for subjects < 18 years may be required per local legislation.
Exclusion Criteria:
- Have clinical, or ultrasound evidence of liver disease. Note: Liver ultrasound at screening is mandatory for MTM1 subjects.
- Presence of significant co-morbidities or conditions other than CNM or clinically significant (CS) findings during screening of medical history, physical examination, laboratory testing, vital signs or ECG recording for which, in the opinion of the investigator and 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).
- For female subjects of child-bearing potential: pregnant or breastfeeding, or planning to become pregnant during the trial.
- Current or past abuse of alcohol or recreational/narcotic drugs (with the exception of caffeine and nicotine), which in the investigator's opinion would compromise the subject's safety and/or compliance with the trial procedures.
- Currently enrolled in any interventional trial or scheduled to participate in such a trial whilst participating in this trial. Subjects are allowed to participate in registry studies.
- Current or relevant history of physical or psychiatric illness, 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 IMP or procedures.
- Intake of any disallowed therapies as noted in Section 5.5 within 12 weeks before the planned first IMP administration.
- Known or suspected intolerance or hypersensitivity to IMP ingredients or closely-related compounds, or history of a significant allergic reaction to IMP ingredients as determined by the investigator, such as anaphylaxis requiring hospitalization.
- Legally incapacitated or have limited legal capacity. Lack of mental capacity to fully understand the protocol requirements and complete all study required procedures.

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): NCT04033159
Contact: Chris Freitag, MD | +33 6 98 75 98 44 | chris.freitag@dynacure.com |
Belgium | |
Antwerp University Hospital (UZA) | Recruiting |
Edegem, Belgium | |
Contact: Jonathan Baets, Professor 0032 3821 5760 jonathan.baets@uza.be | |
Denmark | |
Rigshospitalet, Copenhagen Neuromuscular Center, Neurocentret | Recruiting |
Kopenhagen, Denmark | |
Contact: John Vissing 0045 3545 2562 vissing@rh.dk | |
France | |
Institut de Myologie | Recruiting |
Paris, France | |
Contact: Behin Anthony 0033 142 163 713 anthony.behin@aphp.fr | |
Contact: Tanya Stojkovic 0033 142 163 780 tanya.stojkovic@aphp.fr | |
Germany | |
universitätsklinikum Essen, Kinderklinik I, Sozialpädiatrisches Zentrum | Recruiting |
Essen, Germany | |
Contact: U. Schara, prof. Dr. +49201-723-85170 spz-studienteam@uk-essen.de | |
Contact +49201-723-84601 | |
Friedrich Baur Institut - Neurologische Klinik LMV, Klinikum Innenstadt | Recruiting |
München, Germany | |
Contact: Frederica Montagnese 0049 089 4400 57400 studien.fbi@med.uni-muenchen.de | |
Netherlands | |
Radboud University Medical Centre | Recruiting |
Nijmegen, Netherlands | |
Contact: N.C. Voermans, MD PhD 0031 24 3616 600 nicol.voermans@radboudumc.nl | |
United Kingdom | |
MRC centre for Neuromuscular Disease, National Hospital for Neurology and Neurosurgery | Recruiting |
London, United Kingdom | |
Contact: Rosaline Quinlivan, Professor 0044 7527 442 063 r.quinlivan@ucl.ac.uk | |
Royal Victoria Infirmary | Not yet recruiting |
Newcastle Upon Tyne, United Kingdom | |
Contact: Sam Fitzsimmons 0044 191 241 8649 sam.fitzsimmons@newcastle.ac.uk |
Study Director: | Chris Freitag, MD | Dynacure | |
Principal Investigator: | N.C. Voermans, MD, PhD | Radboud University |
Responsible Party: | Dynacure |
ClinicalTrials.gov Identifier: | NCT04033159 |
Other Study ID Numbers: |
DYN101-C101 |
First Posted: | July 25, 2019 Key Record Dates |
Last Update Posted: | September 30, 2020 |
Last Verified: | July 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Muscular Diseases Myopathies, Structural, Congenital Musculoskeletal Diseases Neuromuscular Diseases Nervous System Diseases |