A study to assess the effect and safety of multiple subcutaneous doses of drisapersen in patients with Duchenne Disease

• Register: EUCTR
• Last refreshed on: 8 August 2016
• Main ID: EUCTR2007-004819-54-BE
• Date of registration: 14/12/2007
• Prospective Registration: Yes
• Primary sponsor: Prosensa Therapeutics BV
• Public title: A study to assess the effect and safety of multiple subcutaneous doses of drisapersen in patients with Duchenne Disease
• Scientific title: A phase I/II, open label, escalating dose, pilot study to assess the effect, safety, tolerability and pharmacokinetics of multiple subcutaneous doses of drisapersen in patients with Duchenne muscular dystrophy and to assess the potential for intravenous dosing as an alternative route of administration
• Date of first enrolment: 22/01/2008
• Target sample size: 12
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-004819-54
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Netherlands, Sweden

Contacts

• Name: Clinical Department
• Affiliation: Prosensa Therapeutics BV

• Name: Clinical Department
• Affiliation: Prosensa Therapeutics BV

Key inclusion & exclusion 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:
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


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

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

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

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
Concentration type: equal
Concentration number: 200-

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
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

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.

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

Secondary Objective: To determine the pharmacokinetics of PRO051 at different dose levels after subcutaneous administration in patients with Duchenne muscular dystrophy.

Timepoint(s) of evaluation of this end point: See Table 4-14 in protocol: schedule of assesments

Secondary Outcome(s)

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

Secondary ID(s)

NCT01254019

NTR1241

PRO051-02

Source(s) of Monetary Support

Prosensa Therapeutics BV