|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Duchenne Muscular Dystrophy
|Medical condition in easily understood language
|Duchenne Muscular Dystrophy (DMD)
|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, tolerability and efficacy of subcutaneous 6mg/kg/week GSK2402968 in subjects with DMD who have participated in either DMD114117 or DMD114044.
|Secondary objectives of the trial
|•To evaluate the long-term PK of subcutaneous 6 mg/kg/week GSK2402968 in subjects with DMD who have participated in either DMD114117 or DMD114044.
•To evaluate the long-term impact on health-related quality of life (HRQoL) and functional outcomes of continued treatment with GSK2402968 in subjects with DMD who have participated in either DMD114117 or DMD114044.
•To evaluate DMD disease progression and outcomes (clinical, HRQoL and functional) in subjects who discontinue active treatment during the conduct of study (natural history component).
•To evaluate the long-term safety, efficacy and PK of an intermittent dosing option in those subjects unable to tolerate GSK2402968 6mg/kg/week dosing.
|Trial contains a sub-study
|Principal inclusion criteria
|Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Subjects who have successfully completed either the DMD114117 study or DMD114044 study, OR
Subjects who withdrew due to safety/tolerability issues, which have since resolved and where in the opinion of the PI along with consultation of the Medical Monitor, it is considered that the benefit of further treatment with GSK2402968 outweighs the risk to the individual subject. OR
Subjects who either complete or withdraw early from studies DMD114117 or DMD114044, who do not wish to continue treatment with GSK2402968 but who are willing to participate in the natural history observation arm.
2. Continued use of glucocorticoids with a reasonable expectation that the subject will remain on steroids for the duration of the study. Changes to or cessation of glucocorticosteroids will be at the discretion of the PI in consultation with the subject/parent and the Medical Monitor.
3. Willing and able to comply with all protocol requirements and procedures,
4. Able to give informed assent and/or consent in writing signed by the subject and/or parent(s)/legal guardian (according to local regulations).
5. French subjects: 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.
|Principal exclusion criteria
|Subjects meeting any of the following criteria must not be enrolled in the study:
1. Subject had a serious adverse experience or who met safety stopping criteria that remains unresolved from DMD114117 or DMD114044, which in the opinion of the investigator could have been attributable to study medication, and which is ongoing at Visit 2. Once resolved, subject may be eligible to enrol following PI consultation with the Medical Monitor.
2. Use of anticoagulants, antithrombotics or antiplatelet agents, or previous treatment with investigational drugs except for GSK2402968, within 1 month of the first administration of study medication.
3. Current or anticipated participation in any other investigational clinical studies
4. History of significant medical disorder which may confound the interpretation of either efficacy or safety data e.g. current or history of renal or liver disease/impairment, history of inflammatory illness.
|E.5 End points
|Primary end point(s)
|Primary efficacy endpoint:
• Muscle function using 6 minute walking distance (6MWD) test.
|Timepoint(s) of evaluation of this end point
|Weeks 12,24,48,72 and Week 104 or Early withdrawal
|Secondary end point(s)
|Secondary efficacy endpoints:
• Timed function tests (times and grading):
• Rise from floor
• 4 stair climb
• 10m walk/run
• Muscle strength (total score): knee flexors, knee extensors, elbow flexors, elbow extensors, shoulder abductors and hip flexors (as determined by handheld myometery)
• North Star Ambulatory Assessment
• Creatine kinase serum concentrations
• Pulmonary function (FEV1, FVC, PCF, PF, sniff pressure test)
• Pediatric Quality of Life Neuromuscular module (PedsQL)
• Clinician Global Impression of Improvement (CGI-I)
• Health Utilities Index (HUI)
• Time to major disease milestones (e.g. loss of ambulation, night time ventilation)
• Frequency of accidental falls (during 6MWD)
• Functional Outcomes assessment
NOTE: A muscle biopsy will be performed only if a case of an unexpected decrease
in efficacy defined as:
- 2 consecutive 20% decreases in 6MWD, after Week 24, in those subjects previously demonstrating improvement or maintenance of 6MWD (unless an alternative explanation can be provided by the investigator e.g. fall), or
- a deterioration in efficacy based on any efficacy parameter which is worse than would be expected based on the natural history of the individual subject, in the opinion of the Investigator
• Incidence and severity of adverse events.
• Vital signs
• ECG parameters
• Safety haematology and biochemistry parameters including non-standard parameters such as coagulation parameters (in particular aPTT), serum cystatin C, Complement Factor C3, haptoglobin, fibrinogen, hsCRP, MCP-1
• Urinalysis (including quantitative protein, creatinine and ratio, urine cystatin, KIM-1 and α1-microglobulin)
• AUC[0-24], AUC[0-7d],
Assess changes in fat infiltration and oedematous inflammation in skeletal muscle in the thigh as determined by structural MRI measures over time in those subjects who had a baseline MRI in the DMD114044 study.
Gait characterisation collected by accelerometry during 6MWD test and free walk test for those subjects where this was performed in the DMD114117 study.
|Timepoint(s) of evaluation of this end point
|Functional secondary endpoints and collection of questionnaires will be performed at the same intervals as the primary endpoint. Samples for urinalysis and safety labs will be collected Baseline and every two weeks thereafter till visit 104 or Early withdrawal. Predose PK samples will be collected monthly. Serial PK at either Week 12 or 48: prior to treatment and 1/2, 2, 4 hours and between 9-12 hours and 48-72 hours after treatment. Vital signs & ECG Weeks 4,8,16,24,32,40,48,60,72,84,96, and Week 104 or Early withdrawal. Echo & DEXA: Weeks 24, 48, 72, and Week 104 or Early withdrawal.
|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
| Information not present in EudraCT
| The trial involves multiple sites in the Member State concerned
| Information not present in EudraCT
|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
|This study has a duration of a minimum of 2 years or until treatment is commercially available locally.
|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