Duchenne Muscular Dystrophy MedDRA version: 17.1 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Drisapersen
Product Code: PRO051
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PRO051
Current Sponsor code: PRO051
Concentration unit: mg/ml milligram(s)/millilitre
Co
Sponsors
Prosensa Therapeutics BV
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Boys aged between 5 and 16 years inclusive 2. Duchenne muscular dystrophy resulting from a mutation correctable by treatment with PRO051 3. Not ventilator dependent 4. Life expectancy of at least 6 months 5. No previous treatment with investigational medicinal treatment within 6 months prior to 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). Are the trial subjects under 18? yes Number of subjects for this age range: 12 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Aberrant RNA splicing and/or aberrant response to PRO051, detected by in vitro PRO051 assay during screening. 2. Known presence of dystrophin in = 5% of fibres 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 0) 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. Subject has donated blood less than 90 days before the start of the study 14. Current or history of drug and/or alcohol abuse 15. Participation in another trial with an investigational product
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Core study: To preliminarily assess the effect of PRO051 at different dose levels in patients with DMD. To assess the safety and tolerability of PRO051 at different dose levels in patients with DMD. To determine the pharmacokinetics of PRO051 at different dose levels after SC administration in patients with DMD. Administration of PRO051 beyond the core study period (SC administration): To assess the effect of PRO051 after SC administration at 6 mg/kg or capped at 300 mg in patients with DMD. To assess the safety and tolerability of PRO051 after SC at 6 mg/kg or capped at 300 mg in patients with DMD. To determine the pharmacokinetics of PRO051 after SC administration at 6 mg/kg in patients with DMD. Administration of PRO051 beyond the core study period (IV administration): IV dosing will be investigated as an alternative route of administration: Please refer to page no.25 of protocol.;Secondary Objective: To determine the pharmacokinetics of PRO051 at different dose levels after subcutaneous administration in patients with Duchenne muscular dystrophy.;Primary end point(s): Effect parameters • Dystrophin expression in muscle biopsy • Exon skip efficiency (RT-PCR on dystrophin mRNA from muscle biopsy and mononuclear blood cells) • Muscle function (timed tests and 6-minutes walk) • Muscle strength (QMT, MMT, handheld myometry, spirometry) Safety • Frequency and number of adverse events • Local tolerability • Complement activation (complement split products C3a, C5a, Bb) • Coagulation (aPTT) • Cytokines (IL-6, TNF-a) and chemokine (MCP-1) • Immune response to dystrophin (antibodies) • ECG, heart rate and blood pressure • Safety haematology and biochemistry parameters • Urinalysis;Timepoint(s) of evaluation of this end point: See Table 4-14 in protocol: schedule of assesments | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacokinetic parameters • t1/2 • AUC: 0-24h, 2hh-7d, 0-8 • Cmax, Ctrough 7d • tmax • distribution volume • clearance;Timepoint(s) of evaluation of this end point: See Table 4-14 in protocol: schedule of assesments | — |
Countries
Belgium, Netherlands, Sweden
Contacts
Public ContactClinical Department
Prosensa Therapeutics BV
Outcome results
None listed