Duchenne Muscular Dystrophy MedDRA version: 20.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: DYNE-251
Product Code: DYNE-251
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: NA
CAS Number: 2725863-42-1
Current Sponsor code: DYNE-251
Other descriptive name: Fragmen
Sponsors
Dyne Therapeutics, Inc
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: • Age 4 to 16 years inclusive, at the time of informed consent/assent. • Male with a confirmed diagnosis of DMD and with a mutation in the dystrophin gene characterized by exon deletion amenable to exon 51 skipping. • Upper extremity muscle group that is amenable to muscle biopsy. • Brooke Upper Extremity Scale score of 1 or 2. • Ambulatory or non-ambulatory. A non-ambulatory participant must have been non-ambulatory for =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Uncontrolled clinical symptoms and signs of congestive heart failure (CHF). • Any change in prophylaxis/treatment for CHF within 3 months prior to the start of study treatment. • History of major surgical procedure within 12 weeks prior to the start of study drug administration or an expectation of a major surgical procedure during the study. • Requirement of daytime ventilator assistance. • Percent predicted FVC <40 % (applies only for participants who are age =7 years). • Receipt of eteplirsen, or alternative exon-skipping/dystrophin-modifying therapy, within 12 weeks of randomization. • Receipt of non-exon skipping investigational drug within 4 months before the start of study drug administration. • Receipt of gene therapy at any time.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of multiple IV doses of DYNE-251 administered to participants with DMD To evaluate dystrophin protein levels in muscle tissue following multiple IV doses of DYNE-251 administered to participants with DMD;Secondary Objective: To evaluate the effects on muscle tissue exon skipping, percent dystrophin-positive fibers (PDPFs), and blood creatine kinase (CK) following multiple IV doses of DYNE-251 administered to participants with DMD To evaluate muscle function following multiple IV doses of DYNE-251 administered to participants with DMD To evaluate plasma and muscle tissue PK following multiple IV doses of DYNE-251 administered to participants with DMD To evaluate the immunogenicity of multiple IV doses of DYNE-251 administered to participants with DMD;Primary end point(s): 1. Number and proportion of participants with treatment-emergent adverse events (TEAEs), treatment emergent serious adverse events (TESAEs), TEAEs considered related to study drug, and TEAEs leading to discontinuation from study drug and discontinuation from the study. 2. Change from Baseline in dystrophin protein levels in muscle tissue as determined by Western blot analysis at Week 25;Timepoint(s) of evaluation of this end point: 1. All visits from screening to end of study 2. Screening and week 25 visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For cohorts dosed on a Q4W or Q8W interval with a second biopsy performed at Week 25: - Change from Baseline in muscle tissue exon 51 skipping levels at Week 25 - Change from Baseline in muscle tissue PDPF at Week 25 - Change from Baseline in blood CK levels up to Week 145 For cohorts dosed on a Q8W interval with a second biopsy performed at Week 49: - Change from Baseline in dystrophin protein levels in muscle tissue as determined by Western blot analysis at Week 49 - Change from Baseline in muscle tissue exon 51 skipping levels at Week 49 - Change from Baseline in muscle tissue PDPF at Week 49 - Change from Baseline in blood CK levels up to Week 145 - Change from Baseline in North Star Ambulatory Assessment (NSAA) total score in ambulatory participants up to Week 145 - Change from Baseline in time to rise from floor in ambulatory participants up to Week 145 - Change from Baseline in 10-meter run/walk (10MRW) time in ambulatory participants up to Week 145 - Change from Baseline in performance upper limb (PUL) scale Version 2.0 score up to Week 145 - Change from Baseline in percent predicted forced vital capacity (FVC) up to Week 145 - Change from Baseline in stride velocity 95th centile (SV95C) in ambulatory participants up to Week 145 - Maximum observed plasma drug concentration (Cmax) - Time to maximum observed plasma drug concentration (tmax) - Area under the plasma drug concentration-time curve (AUC) from time 0 to the last quantifiable concentration (AUCtlast) - Areas under the plasma drug concentration versus time curve from time 0 (dosing) extrapolated to time infinity (AUC8) - Apparent terminal phase elimination rate constant (?Z) - Apparent terminal elimination half-life (t½) - Total body clearance (CL) - Volume of distribution at the terminal phase (Vz), if appropriate - Volume of distribution at steady state (Vss), if appropriate - Tissue phosphorodiamidate morpholino oligomer (PMO) concentration - Incidence of antidrug a | — |
Countries
Australia, Belgium, Canada, Ireland, Italy, Spain, United Kingdom, United States
Contacts
Public ContactDyne Clinical Trials
Dyne Therapeutics, Inc
Outcome results
None listed