Clinical trial NCT01037309: Phase I/II Study of PRO044 in Duchenne Muscular Dystrophy (DMD)
Official title: A Phase I/IIa, Open Label, Escalating Dose, Pilot Study to Assess the Effect, Safety, Tolerability and Pharmacokinetics of Multiple Subcutaneous and Intravenous Doses of PRO044 in Patients With Duchenne Muscular Dystrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Duchenne Muscular Dystrophy
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2009-12-23
Enrollment: 18
Sex: MALE
Minimum age (years): 5
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to see whether PRO044 is safe and effective to use as medication for DMD patients with a mutation around location 44 in the DNA for the dystrophin protein.

Detailed description: To assess the effect of PRO044 at different dose levels in subjects with Duchenne muscular dystrophy To assess the safety and tolerability of PRO044 at different dose levels in subjects with Duchenne muscular dystrophy To determine the pharmacokinetics of PRO044 at different dose levels after subcutaneous and intravenous administration in subjects with Duchenne muscular dystrophy.

Eligibility criteria: Inclusion Criteria:

1. Boys aged between 5 and 16 years inclusive.
2. Duchenne muscular dystrophy resulting from a mutation correctable by treatment with PRO044.
3. Life expectancy of at least 6 months.
4. No previous treatment with investigational medicinal treatment within 6 months prior to the start of the (pre)-screening for the study.
5. No previous treatment with idebenone within 6 months prior to the start of the (pre)-screening for the study.
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 patient, according to the local regulations).
8. Glucocorticosteroids use which is stable for at least 2 months prior first drug administration.

Exclusion Criteria:

1. Aberrant RNA splicing and/or aberrant response to PRO044, detected by in vitro PRO044 assay during pre-screening.
2. Known presence of dystrophin in ≥ 5% of fibers in a pre-study diagnostic muscle biopsy.
3. Severe muscle abnormalities defined as increased signal intensity in \>50% of the tibialis anterior muscle at MRI.
4. FEV1 and/or FVC \< 60% of predicted.
5. Current or history of liver or renal disease.
6. Acute illness within 4 weeks prior to treatment (Day 1) which may interfere with the measurements.
7. Severe mental retardation which in the opinion of the investigator prohibits participation in this study.
8. Severe cardiac myopathy which in the opinion of the investigator prohibits participation in this study.
9. Need for mechanical ventilation.
10. Creatinine concentration above 1.5 times the upper limit of normal (age corrected).
11. Serum ASAT and/or ALAT concentration(s) which suggest hepatic impairment.
12. Use of anticoagulants, antithrombotics or antiplatelet agents.
13. Use of idebenone.
14. Use of any investigational product within 6 months prior to the start of the (pre)-screening for the study.
15. Subject has donated blood less than 90 days before the start of the (pre)-screening for the study.
16. Current or history of drug and/or alcohol abuse.
17. Participation in another trial with an investigational product.

Primary outcomes:
measure: Increase in Dystrophin Expression in the Muscle Biopsies by Immunofluorescence Analyses of Cross-sections and by Western Blot Analyses of Total Protein Extracts
timeFrame: Within 13 weeks after 5 weeks of treatment
measure: Safety and Tolerability of PRO044
timeFrame: During the 5 weeks of treatment and during the 13 weeks after treatment
Secondary outcomes:
measure: PRO044 Pharmacokinetic Cmax (μg/mL) Following Subcutaneous Administration
timeFrame: Week 1, Week 5
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: UZ Leuven
city: Ferrara
country: Italy
facility: S.Anna Hospital
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Gothenburg
country: Sweden
facility: The Queen Silvia Children's Hospital
Study officials:
affiliation: Università di Ferrara and S.Anna Hospital, Ferrara, Italy
name: A. Ferlini, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Leiden University Medical Center, Leiden, the Netherlands
name: J. J. Verschuuren, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UZ Leuven, Leuven, Belgium
name: N. Goemans, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Queen Silvia Children's Hospital, Gothenburg, Sweden
name: M. Tulinius, MD
role: PRINCIPAL_INVESTIGATOR
References: