A clinical study to investigate the pharmacokinetics safety, and tolerability of a single dose of GSK2402968 in non-ambulant subjects with Duchenne muscular dystrophy (GSK Study Number DMD114118)

• Register: EUCTR
• Last refreshed on: 20 March 2012
• Main ID: EUCTR2010-024566-22-Outside-EU/EEA
• Date of registration: 09/03/2012
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research and Development LTD
• Public title: A clinical study to investigate the pharmacokinetics safety, and tolerability of a single dose of GSK2402968 in non-ambulant subjects with Duchenne muscular dystrophy (GSK Study Number DMD114118)
• Scientific title: 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
• Target sample size: 32
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-024566-22
• 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: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

United States

Contacts

• Name: Clinical Trials Helpdesk
• Affiliation: GlaxoSmithKline Research & Development Ltd

• Name: Clinical Trials Helpdesk
• Affiliation: GlaxoSmithKline Research & Development Ltd

Key inclusion & exclusion criteria

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.

Are the trial subjects under 18? yes
Number of subjects for this age range: 32
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).


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Duchenne Muscular Dystrophy
MedDRA version: 14.1 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: GSK2402968
Product Code: GSK2402968
Pharmaceutical Form: Injection
Current Sponsor code: GSK2402968
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)

Secondary Objective: No Secondary objectives

Main Objective: 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.

Timepoint(s) of evaluation of this end point: Day 1, 2, 4, 8 and 29-35 PK
Safety variables as per protocol

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-a and MCP-1) and antibodies to dystrophin.
• Urinalysis: including: protein, creatinine, a1-microglobulin and protein/ creatinine ratio.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Not Applicable

Secondary end point(s): Not Applicable

Secondary ID(s)

DMD114118

Source(s) of Monetary Support

GlaxoSmithKline Research & Development