|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Duchenne Muscular Dystrophy (DMD)
|Medical condition in easily understood language
|Duchenne disease, muscle weakness
|Diseases [C] - Musculoskeletal Diseases [C05]
|E.1.2 Medical condition or disease under investigation
|Duchenne muscular dystrophy
|System Organ Class
|10010331 - Congenital, familial and genetic disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|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.
|Secondary objectives of the trial
|• 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.
|Trial contains a sub-study
|Principal 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).
|Principal 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.
|E.5 End points
|Primary end point(s)
• Incidence and severity of adverse events
• Vital signs
• ECG parameters
• 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)
• Muscle function using 6 minute walking distance (6MWD) test.
• North Star Ambulatory Assessment.
• 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)
|Timepoint(s) of evaluation of this end point
|Secondary end point(s)
|Timepoint(s) of evaluation of this end point
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Korea, Republic of
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days