E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Duchenne Muscular Dystrophy |
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E.1.1.1 | Medical condition in easily understood language |
Duchenne Muscular Dystrophy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10013801 |
E.1.2 | Term | Duchenne muscular dystrophy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the PK, safety and tolerability of GSK2402968 after a single subcutaneous
administration at different dose levels in non-ambulatory subjects with Duchenne
muscular dystrophy. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects eligible for enrolment in the study must meet all of the following criteria:
1. Duchenne muscular dystrophy resulting from a mutation in the DMD gene, confirmed by a sponsor approved DNA diagnostic technique covering all DMD gene exons, including but not limited to MLPA (Multiplex Ligation-dependent Probe
Amplification), CGH (Comparative Genomic Hybridisation), SCAIP (Single
Condition Amplification/Internal Primer) or H-RMCA (High-Resolution Melting
Curve Analysis), and correctable by treatment with GSK2402968.
2. Age 9 years old or greater at Screening;
3. Male;
4. Non-ambulant (at least 1 year in a wheelchair) within the last 4 years;
5. Life expectancy at least three years;
6. Willingness and ability to comply with all protocol requirements and procedures;
7. QTc <450msec (based on single or average QTc value of triplicate ECGs obtained
over a brief recording period). Note: QTc may be either QTcB or QTcF, machine
read or manual overread;
8. Informed assent and/or consent in writing signed by the subject and/or parent(s)/legal guardian (according to local regulations).
9. 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.
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E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria must not be enrolled in the study:
1. Any additional mutation (such as an additional missing exon for DMD) that cannot
be treated with GSK2402968;
2. Current or history of liver or renal disease;
3. Acute illness within 4 weeks of anticipated administration of study medication,
which may interfere with study assessments;
4. Daytime ventilator-dependency (except for daytime naps);
5. Use of anticoagulants, antithrombotics or antiplatelet agents, previous treatment with investigational drugs, within 6 months of the first administration of study
medication; and idebenone or other forms of Coenzyme Q10 within 1 month of study
medication.
6. Start of glucocorticosteroids within 6 months or non-stable use of
glucocorticosteroids within 3 months of the anticipated first administration of study
medication;
7. Positive hepatitis B surface antigen (HbsAg), hepatitis C antibody test (HCV), or
human immunodeficiency virus (HIV) test at Screening;
8. Symptomatic cardiomyopathy;
9. Use of alcohol from Screening through to the 1 month Follow-up visit (Day 29-35,
inclusive);
10. Any Child in Care. (The definition of a Child in Care is a child who has been placed
under the control or protection of an agency, organization, institution or entity by the
courts, the government or a government body, acting in accordance with powers
conferred on them by law or regulation. The definition of a child in care can include
a child cared for by foster parents or living in a care home or institution, provided
that the arrangement falls within the definition above. The definition of a child in
care does not include a child who is adopted or has an appointed legal guardian). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Pharmacokinetic Variables:
• AUC0-24h, AUC0-7d, AUC0-last
• Cmax,
• tmax
• CL/F.
Safety Variables:
• Adverse events
• Physical examination including local tolerability
• Vital signs
• 12-lead ECGs,
• Safety hematology and biochemistry parameters including non-standard
parameters such as coagulation parameters (in particular aPTT), cystatin C,
haptoglobulin, fibrinogen, CRP, complement split products (C3a, SC5b-9, Bb),
inflammation markers (IL-6, TNF-α and MCP-1) and antibodies to dystrophin.
• Urinalysis: including: protein, creatinine, α1-microglobulin and protein/ creatinine ratio.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 1, 2, 4, 8 and 29-35 PK
Safety variables as per protocol
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |