Duchenne Muscular Dystrophy
Conditions
Brief summary
The purpose of this study is to test the safety and tolerability of BMN 351 in participants with Duchenne Muscular Dystrophy (DMD) with a genetic mutation amenable to exon 51 skipping.
Detailed description
This is Phase 1/2, open-label, multi-center study consisting of 2 parts to evaluate the safety and tolerability of BMN 351 at escalating doses in participants with Duchenne Muscular Dystrophy (DMD) with genetic mutations amenable to exon 51 skipping. Participants will be assigned to one of three groups called cohorts (Cohort 1, 2 or 3). Cohort 1 participants are further divided into Cohort 1A and Cohort 1B. In Cohort 1A, 3 participants will receive increasing doses once every 2 weeks with a visit to assess safety measures collected the week after dosing prior to escalating doses of BMN 351. In part 2, the participants in cohort 1A will transition to once weekly dosing. The participants in Cohort 1B, 2, and 3 will initiate low, medium, and high doses of BMN 351 and continue once weekly dosing at that same dose. The study will enroll approximately 18 participants.
Interventions
DRUGBMN 351
Anti-sense Oligonucleotide BMN 351 will be administered intravenously.
Sponsors
BioMarin Pharmaceutical
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
4 Years to 10 Years
Healthy volunteers
No
Inclusion criteria
* Age 4 to 10 * Diagnosis of Duchenne muscular dystrophy with a specific genetic change amenable to exon 51 skipping * Able to walk * Not requiring assistance from a ventilator to breathe * Currently on consistent doses of steroid treatment for the last 12 weeks
Exclusion criteria
* The participant will have some initial clinical labs and studies to assess baseline level of heart and lung function. * Treatment with an exon skipping therapy within 12 weeks prior to the first visit. * Any history of treatment with gene therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate and safety and tolerability of single and multiple doses of BMN 351 (incidence, severity, and dose-relationship of adverse effects and changes in laboratory parameters). | Up to 97 weeks. | The safety and tolerability of BMN 351 will be assessed based on the incidence of adverse and serious adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) concentration of BMN 351 in plasma, urine and muscle approximately every 8 weeks for up to 97 weeks. | Serial measurements pre and post infusion. | Serial measurements of plasma and urine PK predose approximately hourly up to 24 hours post-infusion. Muscle PK will be measured at 13 weeks or 25 weeks only post dosing. |
Countries
Italy, Netherlands, Spain, Turkey (Türkiye), United Kingdom
Outcome results
None listed