A double-blind, escalating dose, randomized, placebo-controlled study to assess the pharmacokinetics, safety and tolerability of single subcutaneous injections of GSK2402968 in non-ambulant subjects with Duchenne muscular dystrophy - N/A

Phase 1

• Conditions: Duchenne Muscular Dystrophy; MedDRA version: 12.1Level: LLTClassification code 10013801Term: Duchenne muscular dystrophy

• Registration Number: EUCTR2010-024566-22-FR
• Lead Sponsor: GlaxoSmithKline Research and Development LTD

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-02-22
• Last Update Posted: 2 October 2017

Recruitment & Eligibility

• Status: A
• Sex: Male
• Target Recruitment: 32

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. Subjects must be willing to use adequate contraception (condoms or abstinence), from Screening until at least 5 months after the last dose of study drug;
9. Informed assent and/or consent in writing signed by the subject and/or parent(s)/legal guardian (according to local regulations).
10 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:
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

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).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the PK, safety and tolerability of GSK2402968 after a single subcutaneous<br>administration at different dose levels in non-ambulatory subjects with Duchenne<br>muscular dystrophy.;Secondary Objective: No Secondary objectives;Primary end point(s): Primary Pharmacokinetic Variables:<br>• AUC0-24h, AUC0-7d, AUC0-last<br>• Cmax,<br>• tmax<br>• CL/F.<br><br>Safety Variables:<br>• Adverse events<br>• Physical examination including local tolerability<br>• Vital signs<br>• 12-lead ECGs,<br>• Safety hematology and biochemistry parameters including non-standard<br>parameters such as coagulation parameters (in particular aPTT), cystatin C,<br>haptoglobulin, fibrinogen, CRP, complement split products (C3a, SC5b-9, Bb),<br>inflammation markers (IL-6, TNF-a and MCP-1) and antibodies to dystrophin.<br>• Urinalysis: including: protein, creatinine, a1-microglobulin and protein/ creatinine ratio.<br><br>