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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biomarin Pharmaceutical Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

8 Mar 2024 → ongoing

Decision date (initial)

2023-12-01

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

BioMarin Pharmaceutical Inc.

External identifiers

EU CT number

2023-506737-30-00

WHO UTN

U1111-1293-4876

ClinicalTrials.gov

NCT06280209

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Safety

To assess the safety and tolerability of BMN 351 at different dose levels in participants with DMD

Secondary objectives 1

1. To evaluate the plasma and urine pharmacokinetics and muscle distribution of BMN 351

Conditions and MedDRA coding

Duchenne Muscular Dystrophy

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, Federal Institute For Drugs And Medical Devices, Medicines Evaluation Board

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Is male and age 4 through 10 years at Screening.
2. 2. Clinical diagnosis of Duchenne muscular dystrophy in the opinion of the investigator resulting from a documented dystrophin mutation in the DMD gene amenable to exon 51 skipping as reviewed by a central genetic counselor.
3. 3. Ambulatory at Screening, defined as able to walk independently without assistive devices and complete the timed 10 meter walk/run test in 8 seconds or less.
4. 4. Not currently daytime ventilator dependent and not expected to need daytime mechanical or noninvasive ventilation within the next year in the opinion of the investigator.
5. 5. Currently receiving treatment with oral corticosteroids or vamorolone, on a stable dose for at least 12 weeks prior to Baseline, and must remain on a consistent dose/dose regimen throughout the study except for modifications to accommodate changes in weight.
6. 6. Normal urinalysis at Screening (trace protein allowed).

Exclusion criteria 7

1. 1. For children 7 years of age or older, forced expiratory volume (FEV1) < 60% of predicted.
2. 2. Current or history of liver or renal disease.
3. 3. Left ventricular ejection fraction (LVEF) < 55% based on an ECHO performed within 3 months prior to the Baseline (Day 1) visit.
4. 4. Mean QT interval corrected with Fridericia’s method (QTcF) ≥ 450 msec on the Screening electrocardiogram (ECG) conducted in triplicate.
5. 5. Platelet count of < 150 x 10^9/L at Screening.
6. 6. Renal function laboratory parameters outside of prespecified values as defined per protocol.
7. 7. Treatment with any exon skipping therapy within 12 weeks prior to Baseline (Day 1) or with any gene therapy for the treatment of DMD at any time.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. 1. Incidence of adverse events/SAEs/AESI, physical examination, safety laboratory test parameters, ECG parameters, echocardiography
2. 2. Physical examination
3. 3. Safety laboratory test parameters
4. 4. ECG parameters

Secondary endpoints 1

1. 1. BMN 351 plasma PK, urine PK and concentration in muscle

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biomarin Pharmaceutical Inc.

Sponsor organisation

Biomarin Pharmaceutical Inc.

Address

105 Digital Drive

City

Novato

Postcode

94949-8703

Country

United States

Scientific contact point

Organisation

Biomarin Pharmaceutical Inc.

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

Biomarin Pharmaceutical Inc.

Contact name

Clinical Trial Information Desk

Third parties 18

Locations

3 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 67 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications