A clinical study to provide drisapersen (study medication) to patients with Duchenne disease (muscular disease) and to assess the safety, tolerability and effect by giving the medication long term.

• Register: EUCTR
• Last refreshed on: 8 August 2016
• Main ID: EUCTR2015-001955-54-NL
• Date of registration: 09/07/2015
• Prospective Registration: Yes
• Primary sponsor: BioMarin Nederland BV
• Public title: A clinical study to provide drisapersen (study medication) to patients with Duchenne disease (muscular disease) and to assess the safety, tolerability and effect by giving the medication long term.
• Scientific title: An open-label extension study of the long-term safety, tolerability and efficacy of drisapersen in subjects with Duchenne Muscular Dystrophy. - Drisapersen extension study
• Date of first enrolment: 08/12/2015
• Target sample size: 220
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001955-54
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Chile, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Norway, Poland, Portugal, Russian Federation, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States, Uruguay

Contacts

• Name: Edith van Dijkman
• Affiliation: BioMarin Nederland BV

• Name: Edith van Dijkman
• Affiliation: BioMarin Nederland BV

Key inclusion & exclusion criteria

Inclusion criteria:
1. Any subject who has been previously treated with an exon 51 skipping antisense oligonucleotide (drisapersen or eteplirsen) and is not eligible for another ongoing drisapersen study. Subjects who withdrew from the previous studies due to meeting laboratory safety stopping criteria may be eligible to enroll if:
a. The laboratory parameters that led to stopping have resolved; benefit of further treatment with drisapersen
outweighs the risk to the individual subject; and following consultation with the Medical Monitor.
2. Subjects with DMD mutation/deletion within the dystrophin gene and correctable by drisapersen-induced DMD exon 51 skipping.
3. Male subjects age >5 with DMD in whom the investigator considers treatment with drisapersen is likely to lead to improvement or prevent worsening of the condition.
4. Continued use of glucocorticoids for a minimum of 60 days prior to study entry with a reasonable expectation that the subject will remain on glucocorticoids for the duration of this study. Changes to or cessation of glucocorticoids will be at the discretion of the investigator conducting this study in consultation with the subject/parent and Medical Monitor.
5. Willing and able to comply with all study requirements and procedures (with the exception of those assessments requiring a subject to be ambulant, for those subjects who have lost ambulation).
6. Able to give informed assent and/or consent in writing by the subject and/or parent(s)/legal guardian (according to local regulations).
Are the trial subjects under 18? yes
Number of subjects for this age range: 215
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 5
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Subjects who have previously been treated with drisapersen and who had a serious adverse experience or who met safety stopping criteria that remains unresolved, which in the opinion of the investigator could have been attributable to drisapersen. Once resolved, subject may be eligible to enter the study following investigator consultation with the Medical Monitor.
2. Use of anticoagulants, anti-thrombotics or antiplatelet agents within 28 days of the first re-dosing of drisapersen. Chronic use of anticoagulants, anti-thrombotics or antiplatelet agents is prohibited during the study. As needed dosing (pro re nata – PRN) may be acceptable (except for aspirin) following discussion with the Medical Monitor.
3. Participation in any investigational clinical trial within 3 months prior to start or during this study (except for other drisapersen studies). If subjects have participated in any other study within the last 6 months this should be discussed with the Medical Monitor prior to start of this study.
4. History of significant medical disorder which may confound the interpretation of safety data (e.g. current or history of renal or liver disease/impairment, history of inflammatory illness)
5. Symptomatic cardiomyopathy. If subject has a left ventricular ejection fraction <45% at start of this study, the investigator should discuss inclusion of subject in this study with the Medical Monitor.
6. A platelet count under the lower limit of normal (LLN) at start of this study. A re-test is possible at a later stage, and if within normal range, the subject may enter the study.



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

Health Condition(s) or Problem(s) studied

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

Duchenne Muscular Dystrophy (DMD)
MedDRA version: 18.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: Drisapersen
Product Code: Drisapersen
Pharmaceutical Form: Solution for injection

Primary Outcome(s)

Secondary Objective: • To evaluate the long-term efficacy of subcutaneous drisapersen at a dose of 6 mg/kg/week.
• To evaluate the long-term impact on functional outcomes of continued treatment with drisapersen.
• To evaluate the long-term safety and efficacy of an intermittent dosing option in those subjects unable to tolerate drisapersen 6 mg/kg/week.
• To evaluate the long-term safety and efficacy of an intravenous dosing option in those subjects unable to tolerate subcutaneous administration of drisapersen.

Timepoint(s) of evaluation of this end point: End of study

Main Objective: To evaluate the long-term safety and tolerability of subcutaneous or intravenous drisapersen in subjects with DMD correctable by drisapersen-induced DMD exon 51 skipping who have previously participated in an eligible study.

Primary end point(s): Study Endpoints/Assessments

Safety Variables:
• Incidence and severity of adverse events
• Vital signs
• ECG parameters
• Echocardiogram
• Injection Site Reactions
• Safety haematology and biochemistry parameters including non-standard parameters such as coagulation parameters (in particular activated partial thromboplastin time [aPTT]), serum cystatin C, Complement Factor C3, haptoglobin, fibrinogen, high-sensitivity C-reactive protein (hsCRP)
• Urinalysis (including quantitative protein and creatinine and their ratio)

Efficacy Variables:
Ambulant subjects
• Muscle function using 6 minute walking distance (6MWD) test.
• North Star Ambulatory Assessment.

All subjects
• Pulmonary function (forced expiratory volume in the 1st second of exhalation [FEV1], forced vital capacity [FVC]). In addition, at selected sites, Maximum Inspiratory Pressure (MIP) and Maximum Expiratory Pressure (MEP) will be assessed.
• Time to major disease milestones (e.g. loss of ambulation, night time ventilation)
• Performance Upper Limb (PUL)
• Patient Reported Outcome Measures (PODCI and EQ-5D-5L)
• MRI (at selected centers)

Secondary Outcome(s)

Secondary end point(s): NA

Timepoint(s) of evaluation of this end point: NA

Secondary ID(s)

DMD

BMN-051-302

Source(s) of Monetary Support

BioMarin Pharmaceuticals Inc.