An early phase human drug trial (called phase 1/2) to investigate DYN101 in patients = 16 years of age with a rare muscle disease group called the centronuclear myopathies caused by genetic changes in DNM2 or MTM1 for the drug’s safety, tolerability, how the body processes the drug as well as interactions of the drug with the body and preliminary effects of the drug.
- Conditions
- Centronuclear myopathies (CNMs) in patients = 16 years of age with mutations in DNM2 or MTM1Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2018-004089-33-NL
- Lead Sponsor
- Dynacure SAS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 18
1. Male or female aged = 16 years on the date of signing the main ICF.
2. Have a documented mutation in DNM2 or MTM1.
3. Meet the following laboratory criteria at screening:
• Platelet count > 150,000/µL,
• Normal kidney function, as determined by values of blood urea nitrogen, creatinine, cystatin C, and estimated glomerular filtration rate within normal laboratory reference ranges,
• Normal liver function, as determined by values of alanine and aspartate aminotransferase, gamma glutamyltransferase, and bilirubin within normal laboratory reference ranges.
4. 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.
5. Have an understanding, ability and willingness to fully comply with visit frequency, trial procedures and restrictions, including contraceptive requirements.
6. 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 6
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2
1. Have clinical, laboratory or ultrasound evidence of liver disease.
Note: Liver ultrasound at screening is mandatory for MTM1 subjects.
2. Presence of significant co-morbidities or conditions other than CNM or clinically significant 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).
3. For female subjects of child-bearing potential: pregnant or breastfeeding, or planning to become pregnant during the trial.
4. Have a body weight of <34 kg.
5. 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.
6. Currently enrolled in another investigational trial or scheduled to participate in another trial whilst participating in this trial.
7. 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.
8. Intake of any disallowed therapies as noted in the protocol within 12 weeks before the planned first IMP administration.
9. 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the safety and tolerability of 3 single ascending dose (SAD) levels and 3 multiple ascending dose (MAD) levels of DYN101;Secondary Objective: • To assess the pharmacokinetics (PK) of SAD and MAD of DYN101.<br>• To explore target engagement in muscle of DYN101.<br>;Primary end point(s): To determine safety and tolerability of SAD and MAD of DYN101, assessed by the number and severity of AEs and SAEs reported from signing of the main ICF onwards until the last trial visit;Timepoint(s) of evaluation of this end point: All visits from baseline to W25 visit and safety follow up call 4 weeks after last dose
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • To determine PK parameters of DYN101 in plasma following SAD and MAD of DYN101.<br>• To assess effects of DYN101 (including DNM2 mRNA levels and DYN101 concentration) in muscle biopsies.<br>;Timepoint(s) of evaluation of this end point: Blood PK: SAD part: Pre-dose (0h), 30 min post start of infusion, 1h, 2h, 4h, 8h, 24h, 48h and 168h post-dose then 2 weeks, 4 weeks, 8 weeks, 12 weeks and 16 weeks post-dose <br>MAD W1 - Pre-dose (0h), 30 min post start of infusion, 1h, 2h, 4h, 8h, 24h, 48h, 72h ( 72h timepoint pre-loading dose) and 168h post-dose<br>MAD W12 - Pre-dose, 30 min post start of infusion, 1h, 2h, 4h, 8h, 24h, 48h, 72h and 168h post-dose of Week 12, Day 1<br>MAD W25 - 168h post-dose of Week 24*<br>Muscle Biopsies:<br>2 time points: At SAD baseline (or at MAD baseline for replaced subjects who did not participate in SAD) and At the end of the 12 weeks MAD part (W13)