Phase I/II Study of PRO044 in Duchenne Muscular Dystrophy (DMD)

Recruitment & Eligibility

Inclusion Criteria

Boys aged between 5 and 16 years inclusive.
Duchenne muscular dystrophy resulting from a mutation correctable by treatment with PRO044.
Life expectancy of at least 6 months.
No previous treatment with investigational medicinal treatment within 6 months prior to the start of the (pre)-screening for the study.
No previous treatment with idebenone within 6 months prior to the start of the (pre)-screening for the study.
Willing and able to adhere to the study visit schedule and other protocol requirements.
Written informed consent signed (by parent(s)/legal guardian and/or the patient, according to the local regulations).
Glucocorticosteroids use which is stable for at least 2 months prior first drug administration.

Exclusion Criteria

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

Study & Design

Arm && Interventions

Group	Intervention	Description
PRO044, cohort 6	PRO044 SC	Subcutaneous injection of maximally 12 mg/kg on day 1, 8, 15, 22 and 29
PRO044, cohort 7	PRO044 IV	Intravenous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29
PRO044, cohort 8	PRO044 IV	Intravenous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29
PRO044, cohort 1	PRO044 SC	Subcutaneous injection of 0.5 mg/kg on day 1, 8, 15, 22 and 29.
PRO044, cohort 3	PRO044 SC	Subcutaneous injection of maximally 5 mg/kg on day 1, 8, 15, 22 and 29.
PRO044, cohort 9	PRO044 IV	Intravenous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29
PRO044, cohort 5	PRO044 SC	Subcutaneous injection of maximally 10 mg/kg on day 1, 8, 15, 22 and 29
PRO044, cohort 4	PRO044 SC	Subcutaneous injection of maximally 8 mg/kg on day 1, 8, 15, 22 and 29.
PRO044, cohort 2	PRO044 SC	Subcutaneous injection of maximally 1.5 mg/kg on day 1, 8, 15, 22 and 29.

Primary Outcome Measures

Name	Time	Method
Increase in Dystrophin Expression in the Muscle Biopsies by Immunofluorescence Analyses of Cross-sections and by Western Blot Analyses of Total Protein Extracts	Within 13 weeks after 5 weeks of treatment
Safety and Tolerability of PRO044	During the 5 weeks of treatment and during the 13 weeks after treatment	number of subjects with 1 or more treatment emergent adverse events following SC or IV PRO044

Secondary Outcome Measures

Name	Time	Method
PRO044 Pharmacokinetic Cmax (μg/mL) Following Subcutaneous Administration	Week 1, Week 5	Pharmacokinetic population evaluated for maximum plasma concentration (Cmax)

Recruitment & Eligibility