A Phase 1/2 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMN 351 in Participants With Duchenne Muscular Dystrophy

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

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.

Study Overview

• Status: Recruiting
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: BMN 351

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.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • Children's Hospital LHSC
      • Principal Investigator: Craig Campbell, MD
      • Contact: Carolyn Twible; Phone Number: 77328 519-685-8500; Email: carolyn.twible@lhsc.on.ca
• Italy
  • Milan, Italy
    • Recruiting
    • Fondazione Serena ETS - Centro Clinico NeMO Milano
    • Principal Investigator: Valeria Sansone
    • Contact: Marta Sorce; Phone Number: +39 3284358826; Email: marta.sorce@centrocliniconemo.it
  • Rome, Italy
    • Recruiting
    • UOC Fase I - Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
    • Principal Investigator: Marika Pane
    • Contact: Celeste Pirozzoli; Phone Number: +39 (0) 630 156 742; Email: mariaceleste.pirozzoli@policlinicogemelli.it
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Recruiting
    • Leids Universitair Medisch Centrum
    • Principal Investigator: Erik Niks
    • Contact: Marjolein Van Heur; Phone Number: +31 71 526 5474; Email: m.j.van_heur-neuman@lumc.nl
• Spain
  • Barcelona, Spain, 08950
    • Recruiting
    • Hospital Sant Joan de Déu
    • Contact: Soraya Peralta; Phone Number: +34 673200068; Email: soraya.peralta@sjd.es
    • Principal Investigator: Andres Nascimento
  • Seville, Spain, 41013
    • Recruiting
    • Hospital Viamed Santa Angela De la Cruz
    • Contact: Carmen Silva; Phone Number: +34 669393637; Email: tuautorapreferida@gmail.com
    • Principal Investigator: Marcos Madruga-Garrido
• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye)
    • Recruiting
    • Yeditepe University Kosuyolu Hospital
    • Principal Investigator: Haluk Topaloglu, MD, Prof
    • Contact: Haluk Topaloglu; Phone Number: 00905322341226; Email: Haluk.topaloglu@yeditepe.edu.tr
• United Kingdom
  • London, United Kingdom, WC1N 3JH
    • Recruiting
    • Great Ormond Street Hospital NHS Foundation Trust
    • Principal Investigator: Giovanni Baranello
    • Contact: Marta Zancolli; Phone Number: +44 (0)20 7905 2188; Email: marta.zancolli@gosh.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 3; BMN 351 high dose will be administered once weekly for up to 48 weeks	Drug: BMN 351; Anti-sense Oligonucleotide BMN 351 will be administered intravenously.
Experimental: Cohort 1A; 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 89 weeks.	Drug: BMN 351; Anti-sense Oligonucleotide BMN 351 will be administered intravenously.
Experimental: Cohort 1B; BMN 351 low dose will be administered once weekly for up to 97 weeks	Drug: BMN 351; Anti-sense Oligonucleotide BMN 351 will be administered intravenously.
Experimental: Cohort 2; BMN 351 medium dose will be administered once weekly for up to 73 weeks	Drug: BMN 351; Anti-sense Oligonucleotide BMN 351 will be administered intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	The safety and tolerability of BMN 351 will be assessed based on the incidence of adverse and serious adverse events.	Up to 97 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) concentration of BMN 351 in plasma, urine and muscle approximately every 8 weeks for up to 97 weeks.	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.	Serial measurements pre and post infusion.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the effect of BMN 351 on physical function.	Change from baseline on 6 Minute Walk Test (6MWT).	Change from baseline at week 25.
To evaluate the effect of BMN 351 on physical function.	Change from baseline on North Star Ambulatory Assessment (NSAA).	Change from baseline at week 25.
Change from baseline in dystrophin expression measured by Liquid chromatography-mass spectrometry (LC-MS).		Baseline, Week 13 or Week 25
To evaluate the immune response to BMN 351.	Anti-BMN 351 antibodies, anti-dystrophin antibodies.	Up to 97 weeks

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: January 26, 2024
• First Submitted That Met QC Criteria: February 20, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Muscular Disorders, Atrophic; Muscular Dystrophies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: 351-201; 2023-506737-30-00 (Other Identifier: EU CT)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No