A phase III, randomized, double blind, placebo-controlled clinical study to assess the efficacy and safety of GSK2402968 in subjects with Duchenne muscular dystrophy. - N/A

• Register: EUCTR
• Last refreshed on: 5 August 2013
• Main ID: EUCTR2010-020069-26-NL
• Date of registration: 04/11/2010
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research and Development LTD
• Public title: A phase III, randomized, double blind, placebo-controlled clinical study to assess the efficacy and safety of GSK2402968 in subjects with Duchenne muscular dystrophy. - N/A
• Scientific title: A phase III, randomized, double blind, placebo-controlled clinical study to assess the efficacy and safety of GSK2402968 in subjects with Duchenne muscular dystrophy. - N/A
• Date of first enrolment: 02/03/2011
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-020069-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Belgium, Czech Republic, Denmark, France, Germany, Hungary, Italy, Netherlands, Poland, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1. Ambulant subjects with Duchenne muscular dystrophy resulting from a
mutation/deletion within the DMD gene, confirmed by a state-of-the-art 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
GSK2402968-induced DMD exon 51 skipping.

2. Males, aged at least 5 years,

3. Life expectancy of at least 1 year,

4. Able to complete 6MWD test with minimal distance of at least 75m at each predrug
visit. In addition, results of 6MWD must be within 20% of each other at each
pre-drug visit.

5. Receiving glucocorticoids for a minimum of 6 months immediately prior to
screening, with no significant change in total daily dosage or dosing regimen for a
minimum of 3 months immediately prior to screening and a reasonable
expectation that total daily dosage and dosing regimen will not change
significantly for the duration of the study,

6. QTc <450msec (based on single or average QTc value of triplicate ECGs obtained
over a brief recording period), or <480 msec for subjects with Bundle Branch
Block. Note: QTc may be either QTcB or QTcF, and machine read or manual
overread.

7. Subjects, where appropriate, must be willing to use adequate contraception
(condoms or abstinence) for the duration of the study and for at least 5 months
after the last dose of study drug.

8. Willing and able to comply with all protocol requirements and procedures,

9. Able to give informed assent and/or consent in writing signed by the subject
and/or parent(s)/legal guardian (according to local regulations).

10. 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.
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 missing exon for DMD that cannot be treated with GSK2402968

2. Current or history of liver or renal disease or impairment

3. Acute illness within 4 weeks of the first anticipated administration of study
medication which may interfere with study assessments

4. 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
the first administration of study medication.

5. Current or anticipated participation in any investigational clinical studies

6. Positive hepatitis B surface antigen, hepatitis C antibody test (if verified via RIBA
or PCA testing), or human immunodeficiency virus (HIV) test at screening,

7. Symptomatic cardiomyopathy. If subject has a left ventricular ejection fraction
<45% at Screening, the investigator should discuss inclusion of subject in the
study with the medical monitor,

8. Children in Care. The definition of a Child in Care is a child who has been placed
under the control or protection of an agency, organisation, 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: 12.1 Level: LLT Classification code 10013801 Term: Duchenne muscular dystrophy

Intervention(s)

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: Injection*
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): The primary endpoint is the mean change from baseline in the 6MWD and results will be compared between active and placebo groups using statistical hypothesis testing.
The primary time point of interest will be the end of treatment (Week 48). Confirmatory statistical testing will be performed only for the primary variable, analysed using the ITT analysis population, therefore, no adjustments for multiplicity are required. A 5%
significance level will be used to determine a statistically significant difference.

Secondary Objective: To evaluate the safety and tolerability of subcutaneous 6 mg/kg GSK2402968
versus placebo administered over 48 weeks in ambulant subjects with DMD.
• To evaluate the PK of subcutaneous 6 mg/kg GSK2402968 administered over 48
weeks in ambulant subjects with DMD.
• To evaluate the impact on quality of life of GSK2402968 administered over 48
weeks in ambulant subjects with DMD.

Main Objective: To assess the efficacy of subcutaneous 6 mg/kg GSK2402968 versus placebo
administered over 48 weeks in ambulant subjects with DMD.

Secondary ID(s)

2010-020069-26-DE

DMD114044