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

Duchenne Muscular Dystrophy Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06280209
• Other study ID #: 351-201
• Secondary ID: 2023-506737-30-0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 3, 2024
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Years to 10 Years

Eligibility

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

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• BMN 351
Anti-sense Oligonucleotide BMN 351 will be administered intravenously.

Locations

Country	Name	City	State
Italy	Fondazione Serena Onlus - Centro Clinico NeMO Milano	Milan
Italy	UOC Fase I - Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore	Rome
Spain	Hospital Sant Joan de Deu	Barcelona
Spain	Hospital Viamed Santa Angela De la Cruz	Sevilla
Turkey	Yeditepe University Kosuyolu Hospital	Istanbul
United Kingdom	Great Ormond Street Hospital NHS Foundation Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Countries where clinical trial is conducted

Italy,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To evaluate the immune response to BMN 351.	Anti-BMN 351 antibodies, anti-dystrophin antibodies.	Up to 56 weeks
Other	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.
Other	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.
Other	Change from baseline in dystrophin expression measured by Liquid chromatography-mass spectrometry (LC-MS).		Baseline, Week 13 or Week 25
Primary	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 73 weeks.
Secondary	Pharmacokinetics (PK) concentration of BMN 351 in plasma, urine and muscle approximately every 8 weeks for up to 48 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.