Phase IIb Study of PRO045 in Subjects With Duchenne Muscular Dystrophy

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01826474
• Date of registration: 20/03/2013
• Prospective Registration: No
• Primary sponsor: BioMarin Pharmaceutical
• Public title: Phase IIb Study of PRO045 in Subjects With Duchenne Muscular Dystrophy
• Scientific title: A Phase IIb, Open-label Study to Assess the Efficacy, Safety, Pharmacodynamics and Pharmacokinetics of Multiple Subcutaneous Doses of PRO045 in Subjects With Duchenne Muscular Dystrophy
• Date of first enrolment: January 2013
• Target sample size: 15
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT01826474
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Belgium, France, Italy, Netherlands, United Kingdom

Contacts

• Name: T. Voit, MD PhD
• Affiliation: Institut de Myologie

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Duchenne muscular dystrophy resulting from a mutation correctable by treatment with
PRO045 confirmed by a state-of-the-art DNA diagnostic technique covering all DMD gene
exons, including but not limited to MLPA (Multiplex Ligation-dependent Probe
Amplification), CGH (Comparative Genomic Hybridisation), SCAIP (Single Condition
Amplification/Internal Primer) or HRMCA (High-Resolution Melting Curve Analysis), and
correctable by PRO045-induced DMD exon 45 skipping in cultured skin-derived
myo-converted fibroblasts.

2. Ambulant boys aged at least 5 years on the day of first dosing able to walk for at
least 230 meters in the 6 minute walking distance (6MWD) test at first screening visit
and also at the baseline visit. In addition, 2 of the 3 pre-treatment 6MWD tests
(screen 1, screen 2, baseline) must be within +/-30 metres of each other prior to
first PRO045 administration.

3. Adequate quality for biopsy (confirmed with MRI) of the lateral head of the
gastrocnemius muscle. An alternative muscle may be considered for biopsy but only
following discussion between the Principal Investigator and the Prosensa Medical
Monitor.

4. Life expectancy of at least 3 years after inclusion in the study.

5. Glucocorticosteroid use which is stable for at least 3 months prior to first PRO045
administration. Subjects must have been receiving glucocorticosteroids for at least 6
months prior to the first PRO045 administration.

6. Willing and able to adhere to the study visit schedule and other protocol
requirements.

7. Written informed consent signed (by parent(s)/legal guardian and/or the subject,
according to the local regulations).

8. In France, a subject will be eligible for inclusion in this study only if either
affiliated to, or a beneficiary of, a social security category.

Exclusion Criteria:

1. Known presence of dystrophin in =5% of fibres in a pre-study diagnostic muscle biopsy
(i.e. historic muscle biopsy taken prior to written informed consent for this study).

2. Current or history of liver disease or impairment.

3. Current or history of renal disease or impairment.

4. At least two aPTT above ULN within the last month.

5. Screening platelet count below the lower limit of normal (LLN).

6. Acute illness within 4 weeks prior to first dose of PRO045 which may interfere with
the study assessments.

7. Severe mental retardation or behavioural problems which in the opinion of the
investigator prohibits participation in this study.

8. Severe cardiomyopathy which in the opinion of the investigator prohibits participation
in this study. If a subject has a left ventricular ejection fraction <45% at
screening, the investigator should discuss inclusion of the subject with the Medical
Monitor.

9. Expected need for daytime mechanical ventilation within the next year.

10. Use of anticoagulants, antithrombotics or antiplatelet agents.

11. Use of idebenone or other forms of coenzyme Q10 within 1 month prior to the start of
the screening for the study.

12. Use of nutritional or herbal supplements which, in the opinion of the investigator,
may influence muscle performance, within 1 month of the study.

13. Use of any other investigational product or participation in another trial with an
investigational product, within 6 months prior to the start of the screening for the
study.



Age minimum: 5 Years
Age maximum: 18 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Duchenne Muscular Dystrophy

Intervention(s)

Drug: PRO045, 3.0 mg/kg/week

Drug: PRO045, 6.0 mg/kg/week

Drug: PRO045, selected dose

Drug: PRO045, 0.15 mg/kg/week

Drug: PRO045, 1.0 mg/kg/week

Drug: PRO045, 9.0 mg/kg/week

Primary Outcome(s)

Change from baseline in 6 minute walk test [Time Frame: after 48 weeks of treatment phase]

Secondary Outcome(s)

Muscle function [Time Frame: after 48 weeks of treatment phase]

Performance of upper limb [Time Frame: after 48 weeks of treatment phase]

Safety [Time Frame: after 48 weeks of treatment phase]

Functional outcomes questionnaire [Time Frame: after 48 weeks of treatment]

Muscle strength [Time Frame: after 48 weeks treatment phase]

Secondary ID(s)

PRO045-CLIN-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors