Centronuclear myopathies (CNMs) in subjects = 16 years of age with mutations in DNM2 or MTM1 MedDRA version: 20.0 Level: HLT Classification code 10028640 Term: Myopathies System Organ Class: 100000004859
Conditions
Interventions
Product Name: DYN101
Product Code: DYN101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DYN101
Current Sponsor code: DYN101
Concentration unit: mg/ml milligram(s)/mil
Sponsors
Dynacure
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female aged = 16 years of age* on the date of signing the main ICF. The first subject (i.e. the sentinel subject) in each cohort must be = 18 years of age. *for Germany, the subject must be = 18 years of age in accordance with local and national regulations. 2. Have a documented mutation in DNM2 or MTM1. 3. Platelet count > 150,000/µL. 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 4 relevant domains that will be investigated in this trial (respiratory function, muscle strength, muscle function and 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 =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1. Clinically significant liver disease. 2. Clinically significant renal disease. 3. 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). 4. For female subjects of child-bearing potential: pregnant or breastfeeding, or planning to become pregnant during the trial. 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 any interventional trial or scheduled to participate in such a trial whilst participating in this trial. Subjects are allowed to participate in registry studies. 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. 10. Legally incapacitated or have limited legal capacity. Lack of mental capacity to fully understand the protocol requirements and complete all study required procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. • To explore target engagement in muscle of DYN101. ;Primary end point(s): Comparison of adverse event (AE, SAE, AESI) frequency and severity by dose (cohort), for single or multiple administration, and by mutated gene (sub-cohort) and overall using the Safety Analysis Set following 12 weeks of MAD treatment and after 24 weeks of MAD treatment (12 weeks in the MAD part + 12 weeks in the MAD extension part; Week 25 visit) or discontinued earlier.;Timepoint(s) of evaluation of this end point: All visits from baseline to W25 visit and safety End-of-Treatment follow up visit 3 months after last dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Comparison of means for PK parameters of DYN101 in plasma (AUCt, AUClast, AUC8, Rac(AUC), Rac(Cmax), Cmax, Cav SS, CL, ?z, t1/2, tmax, Vz) by dose (cohort), for single or multiple administration, and by mutated gene (sub-cohort) and overall using the Pharmacokinetic Set. • Comparison of geometric means for PK parameters of DYN101 in plasma (Cmax and AUCs) by dose (cohort), for single or multiple administration, and by mutated gene (sub-cohort) and overall using the Pharmacokinetic Set. • Comparison of means on DNM2 mRNA levels and DYN101 concentrations using muscle biopsy data by dose (cohort), for single or multiple administration, and by mutated gene (sub-cohort) and overall using the Pharmacokinetic Set. • Comparison of means change from baseline in vital signs, laboratory data, and ECG by dose (cohort), for single or multiple administration, and by mutated gene (sub-cohort) and overall.;Timepoint(s) of evaluation of this end point: SAD part: Pre-dose (0h), 30 min post start of infusion, immediately after end of infusion, 1h, 3h, 7h, 23h, 47h, 167h post-dose then 2 weeks, 4 weeks, 8 weeks, 12 weeks and 16 weeks post-dose MAD W1 - Pre-dose (0h), 30 min post start of infusion, immediately after end of infusion, 1h, 3h, 7h, 23h, 47h, 71h ( 71h timepoint pre-loading dose) and 167h post-dose MAD W12 - Pre-dose, 30 min post start of infusion, immediately after end of infusion, 1h, 3h, 7h, 23h, 71h and 167h post-dose of Week 12, Day 1 MAD W25 - 167h post-dose of Week 24* Muscle Biopsies: 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) | — |
Countries
Belgium, Denmark, France, Germany, Netherlands, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Dynacure
Outcome results
None listed