A Phase 1/2 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMN 351 in Participants with Duchenne Muscular Dystrophy
- Registration Number
- NCT06280209
- Lead Sponsor
- BioMarin Pharmaceutical
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 18
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 1A BMN 351 Cohort 1A will consist of both a single ascending dose (SAD) part and a multiple ascending dose (MAD). BMN 351 will be administered once every 2 weeks during the SAD portion of the study for up to 8 weeks and once weekly during the MAD portion for up to 56 weeks. Cohort 1B BMN 351 BMN 351 low dose will be administered once weekly for up to 48 weeks Cohort 2 BMN 351 BMN 351 medium dose will be administered once weekly for up to 48 weeks Cohort 3 BMN 351 BMN 351 high dose will be administered once weekly for up to 48 weeks
- Primary Outcome Measures
Name Time Method 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 73 weeks. The safety and tolerability of BMN 351 will be assessed based on the incidence of adverse and serious adverse events.
- Secondary Outcome Measures
Name Time Method Pharmacokinetics (PK) concentration of BMN 351 in plasma, urine and muscle approximately every 8 weeks for up to 48 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.
Trial Locations
- Locations (7)
Leids Universitair Medisch Centrum
🇳🇱Leiden, Netherlands
Yeditepe University Kosuyolu Hospital
🇹🇷Istanbul, Turkey
Great Ormond Street Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
Fondazione Serena Onlus - Centro Clinico NeMO Milano
🇮🇹Milan, Italy
UOC Fase I - Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
🇮🇹Rome, Italy
Hospital Sant Joan de Deu
🇪🇸Barcelona, Spain
Hospital Viamed Santa Angela De la Cruz
🇪🇸Sevilla, Spain