Clinical trial NCT06280209: A Phase 1/2 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMN 351 in Participants with Duchenne Muscular Dystrophy
Official title: A Phase 1/2, Open-Label, Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Intravenous Doses of BMN 351 in Participants with Duchenne Muscular Dystrophy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Duchenne Muscular Dystrophy
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2024-02-28
Enrollment: 18
Sex: MALE
Minimum age (years): 4
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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).
timeFrame: Up to 73 weeks.
Secondary outcomes:
measure: Pharmacokinetics (PK) concentration of BMN 351 in plasma, urine and muscle approximately every 8 weeks for up to 48 weeks.
timeFrame: Serial measurements pre and post infusion.
Other outcomes:
measure: To evaluate the immune response to BMN 351.
timeFrame: Up to 56 weeks
measure: To evaluate the effect of BMN 351 on physical function.
timeFrame: Change from baseline at week 25.
measure: To evaluate the effect of BMN 351 on physical function.
timeFrame: Change from baseline at week 25.
measure: Change from baseline in dystrophin expression measured by Liquid chromatography-mass spectrometry (LC-MS).
timeFrame: Baseline, Week 13 or Week 25
Locations:
city: Milan
country: Italy
facility: Fondazione Serena Onlus - Centro Clinico NeMO Milano
city: Rome
country: Italy
facility: UOC Fase I - Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu
city: Sevilla
country: Spain
facility: Hospital Viamed Santa Angela De la Cruz
city: Istanbul
country: Turkey
facility: Yeditepe University Kosuyolu Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital NHS Foundation Trust
Study officials:
References: