A clinical study to provide drisapersen (study medication) to patients with Duchenne disease (muscular disease) and to assess the efficacy, safety and tolerability.

• Register: EUCTR
• Last refreshed on: 8 August 2016
• Main ID: EUCTR2014-005296-81-BE
• Date of registration: 19/11/2015
• Prospective Registration: Yes
• Primary sponsor: BioMarin Pharmaceutical Inc.
• Public title: A clinical study to provide drisapersen (study medication) to patients with Duchenne disease (muscular disease) and to assess the efficacy, safety and tolerability.
• Scientific title: A 24 week Randomized Double-Blind, Placebo-Controlled Study followed by 72 week open-label extension to assess the efficacy, safety and tolerability of drisapersen sodium in subjects with Duchenne Muscular Dystrophy - Drisapersen confirmatory study
• Date of first enrolment: 02/05/2016
• Target sample size: 104
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-005296-81
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: The initial 24-week double-blind study is followed by 72-week open-label extension study. If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, Czech Republic, France, Germany, Israel, Italy, Japan, Poland, Russian Federation, Spain, Sweden, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Trials Information
• Affiliation: BioMarin Pharmaceutical Inc

• Name: Clinical Trials Information
• Affiliation: BioMarin Pharmaceutical Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Ambulant subjects with DMD resulting from a mutation/deletion within the dystrophin gene, confirmed by a Deoxyribonucleic acid (DNA) diagnostic technique covering all dystrophin gene exons (e.g. MLPA, CGH, SCAIP, H-RMCA) and correctable by drisapersen sodium-induced exon 51 skipping.

2. Male subjects aged =5 years at Screening.

3. Able to Rise from Floor in = 7 seconds on at least 2 of the 3 pre-treatment visits (screening 1, screening 2, and baseline).

4. Able to walk at least 300m on the 6MWD on at least 2 of the 3 pre-treatment visits (screening 1, screening 2, and baseline).

5. Glucocorticosteroid use which is stable for at least 3 months prior to the first screening visit. Subjects must have been receiving glucocorticosteroids for at least 6 months prior to the first screening visit.

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 subject, according to the local regulations).

8. In France, a subject will be eligible for inclusion in this study only if either affiliated to, or a beneficiary of, a social security category.
Are the trial subjects under 18? yes
Number of subjects for this age range: 104
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. More than a 30º (degree) flexion of either ankle, measure by goniometry.

2. Any additional mutations for DMD that cannot be treated by drisapersen sodium.

3. Current or history of liver or renal disease or impairment.

4. Screening platelet count below the lower limit of normal (LLN).

5. Acute illness within 4 weeks prior to first study drug administration which may interfere with the study assessments.

6. History of significant medical disorder which may confound the interpretation of efficacy or safety data (e.g. inflammatory disease, severe mental retardation and/or behavioral problems).

7. Severe cardiomyopathy which, in the opinion of the Investigator prohibits participation in this study. If a subject has a left ventricular ejection fraction <45% at screening, the Investigator should discuss inclusion of the subject with the Medical Monitor.

8. Chronic use of anti-coagulants, anti-thrombotics or anti-platelet agents within 1 month of the first administration of study drug.

9. Use of idebenone or other forms of coenzyme Q10 within 1 month prior to the start of the screening for the study.

10. Use of any investigational product or participation in another trial with an investigational product, within the half-life of that investigational product or a minimum of 6 months prior to the start of screening for the study.

11. Previous use of drisapersen sodium or eteplirsen.

12. NOTE: Subjects who fail on an entry criterion (apart from those subjects deemed to be ineligible for safety reasons) may be allowed to be re-screened at a later date, following discussion with the Medical Monitor.


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: 18.1 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
INN or Proposed INN: Drisapersen
CAS Number: 1251830-50-8
Current Sponsor code: BMN-051
Other descriptive name: DRISAPERSEN SODIUM
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): Efficacy

• Change from Baseline at Week 24 in the 6MWD drisapersen sodium group compared to the placebo control group.

Secondary Objective: Secondary objectives

• To investigate the safety of drisapersen sodium administered for 24 weeks compared to placebo control group in ambulant subjects with DMD.

• To investigate the efficacy of drisapersen sodium administered to ambulant subjects with DMD for 96 weeks compared to a natural history control cohort.

• To compare the efficacy of drisapersen treatment from the start of the study to delayed drisapersen treatment (placebo subjects who have crossed over to drisapersen treatment post-24 weeks) at 48 and 96 weeks.

• To investigate the safety and tolerability of drisapersen sodium administered to ambulant subjects with DMD for 96 weeks.

Timepoint(s) of evaluation of this end point: at week 24

Main Objective: • To investigate the efficacy of drisapersen sodium administered for 24 weeks compared to a placebo control group in ambulant subjects with DMD.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Efficacy Endpoints:

1. at Week 24

2. at Week 96 and other time points

3. 48 weeks and 96 weeks


Exploratory Endpoints:

1. at Week 48

2. over 96 weeks

Secondary end point(s): Efficacy:

Change from Baseline, drisapersen sodium group compared to the placebo control group in:

• Percent predicted 6MWD

• North Star Ambulatory Assessment (NSAA)

• Rise from floor (assessed as part of NSAA)

• 10m walk/run (assessed as part of NSAA)

• 4-Stair Climb (ascent and descent)

• Pathological changes in skeletal muscle identified by Magnetic Resonance Imaging (MRI)/Magnetic Resonance Spectroscopy (MRS)

• Creatine kinase

• Pulmonary function

2. Change from Baseline, drisapersen sodium group compared to the natural history control group in:

• Absolute 6MWD

• Percent predicted 6MWD

• NSAA

• Rise from floor (assessed as part of NSAA)

• 10m walk/run (assessed as part of NSAA)

• 4-Stair Climb (ascent and descent)

• Pathological changes in skeletal muscle identified by Magnetic Resonance Imaging (MRI)/Magnetic Resonance Spectroscopy (MRS)

• Creatine kinase

• Pulmonary function

• Time to major disease milestones (e.g. loss of ambulation)

3. Change from Baseline, drisapersen sodium group compared to placebo/delayed drisapersen sodium group :

• Absolute 6MWD

• Percent predicted 6MWD

• NSAA

• Rise from floor (assessed as part of NSAA)

• 10m walk/run (assessed as part of NSAA)

• 4-Stair Climb (ascent and descent)

• Pathological changes in skeletal muscle identified by Magnetic Resonance Imaging (MRI)/Magnetic Resonance Spectroscopy (MRS)

• Creatine kinase

• Pulmonary function

• Time to major disease milestones (e.g. loss of ambulation)

Exploratory Endpoints:

1. Change from Baseline, drisapersen sodium group compared to a historical matched placebo population (from the drisapersen sodium PCTs) in:

• Absolute 6MWD

• Percent predicted 6MWD

• NSAA

• Rise from floor (assessed as part of NSAA)

• 10m walk/run (assessed as part of NSAA)

• 4-Stair Climb (ascent and descent)

• Creatine kinase

• Pulmonary function

• Biomarkers of disease progression (based on ongoing work)

Change from Baseline in:

• Quality of life – PODCI, NeuroQoL (physical domains), EQ5D-5L


2. Change from Baseline and compared to a natural history cohort:

• Exploratory biomarkers of disease progression (e.g., proteins from muscle, LDH, 6 phosphogluconate dehydrogenase, vascular endothelium E-cadkerin, miRNA-1, miRNA-133, triglycerides) (based on ongoing work)

Secondary ID(s)

DMD

BMN-051-303

Source(s) of Monetary Support

BioMarin Pharmaceutical Inc.