Last updated: 07/17/2024 15:41:44
A clinical study to assess two doses of GSK2402968 in subjects with Duchenne muscular dystrophy (DMD)DMD114876
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: An exploratory study to assess two doses of GSK2402968 in the Treatment of Ambulant boys with Duchenne Muscular Dystrophy
Trial description: The purpose of this study is to determine if GSK2402968 is effective in the treatment of ambulant boys with Duchenne muscular dystrophy resulting from a mutation thought to be corrected by exon 51 skipping. Two doses of GSK2402968 and placebo will be used in this study.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Mean change from Baseline in muscle function using the 6 minute walking distance
Timeframe: Baseline (Week 0) and Week 24
Secondary outcomes:
Change from Baseline in Rise from floor time at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in 4 stair climb ascent/descent time at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in 10 meter walk/run at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in muscle strength total score at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in muscle strength tests for-Knee extensor, knee flexor, hip flexor, elbow flexor, elbow extensor, shoulder abductor at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from baseline in the North Star Ambulatory Assessment (NSAA) total score
Timeframe: Baselie (Week 0) and Week 24
Number of participants with accidental falls during 6 minute walk distance test
Timeframe: Baseline (Week 0), Week 24, Week 36 and Week 48
Change from baseline in creatinine kinase serum concentrations
Timeframe: Baseline (Week 0) and Week 48
Change from baseline in Forced expiratory volume in the first second of exhalation (FEV1) at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in forced vital capacity (FVC) at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from baseline in peak cough flow at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from Baseline in peak expiratory flow at Week 24
Timeframe: Baseline (Week 0) and Week 24
Change from baseline in sniff pressure test at Week 24
Timeframe: Baseline (Week 0) and Week 24
Number of participants with change from baseline in Dystrophin expression at Week 24 by Immunofluorescence assay (IFA)
Timeframe: Baseline (Week 0) and Week 24
Number of Clinician Global Impression of Improvement (CGI-I) responders
Timeframe: Week 24 and Week 48
Assessment of functional outcome by : Functional Outcomes Survey during treatment period
Timeframe: Up to Week 24
Assessment of functional outcome by : Physician assessment of daily living
Timeframe: Week 24 and Week 48
Interventions:
Drug: GSK2402968 3mg/kg/week
Drug: GSK2402968 6 mg/kg/week
Drug: Placebo to match GSK2402968 3 mg/kg/week
Drug: Placebo to match GSK2402968 6 mg/kg/week
Enrollment:
51
Observational study model:
Not applicable
Primary completion date:
2013-21-05
Time perspective:
Not applicable
Clinical publications:
McDonald CM, Wong B, Flanigan KM, Wilson R de Kimpe S, Lourbakos A Lin Z, Campion G. Placebo-controlled Phase 2 Trial of Drisapersen for Duchenne Muscular Dystrophy.. Muscle Nerve. 2018;5(8):913-926
Medical condition
Muscular Dystrophies
Product
drisapersen
Collaborators
Not applicable
Study date(s)
October 2011 to November 2013
Type
Interventional
Phase
2
Participation criteria
Sex
Male
Age
5+ years
Accepts healthy volunteers
No
- Ambulant subjects with Duchenne muscular dystrophy (DMD) 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
- Males, aged at least 5 years,
- Any additional missing exon for DMD that cannot be treated with GSK2402968,
- Current or history of liver disease or impairment including :
Inclusion and exclusion criteria
Inclusion criteria:
- Ambulant subjects with Duchenne muscular dystrophy (DMD) 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
- Males, aged at least 5 years,
- Life expectancy of at least 1 year,
- Able to rise from floor in < or =15 seconds (without aids/orthoses) at Screening Visit 1 and Screening Visit 2,
- Able to complete 6 Minute Walk Distance (6MWD) test with minimal distance of at least 75 meters, with reproducible results (within 20% of each other) at Screening Visit 1, Screening Visit 2 and at the baseline visit prior to randomization,
- Receiving oral 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 48 week duration of the study (Dose adjustments that are based on weight changes are permitted),
- 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
- Willing and able to comply with all protocol requirements and procedures,
- Able to give informed assent and/or consent in writing signed by the subject and/or parent(s)/legal guardian (according to local regulations).
Exclusion criteria:
- Any additional missing exon for DMD that cannot be treated with GSK2402968,
- Current or history of liver disease or impairment including : a. an INR vaue above 1.5 is in and of itself exclusionary b. a total bilirubin greater than 2 times the Upper Limit of Normal is in and of itself exclusionary c. a GGT greater than 2 times the Upper Limit of Normal is in and of itself exclusionary
- Current or history of renal disease or impairment,
- Baseline platelet count below the Lower Limit of Normal,
- aPPT above the Upper Limit of Normal,
- History of significant medical disorder which may confound the interpretation of either efficacy or safety data e.g. inflammatory disease
- Acute illness within 4 weeks of the first anticipated administration of study medication which may interfere with study assessments,
- Use of anticoagulants, antithrombotics or antiplatelet agents, previous treatment with investigational drugs, idebenone or other forms of Coenzyme Q10 within 1 month of the first administration of study medication,
- Current or anticipated participation in any investigational clinical studies,
- Positive hepatitis B surface antigen, hepatitis C antibody test (if verified via RIBA or PCA testing), or human immunodeficiency virus (HIV) test at screening,
- 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,
- 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
Trial location(s)
Location
GSK Investigational Site
Baltimore, Maryland, United States, 21205
Status
Study Complete
Location
GSK Investigational Site
Cincinnati, Ohio, United States, 45229
Status
Study Complete
Location
GSK Investigational Site
Durham, North Carolina, United States, 27710
Status
Study Complete
Location
GSK Investigational Site
Gulf Breeze, Florida, United States, 32561
Status
Study Complete
Location
GSK Investigational Site
Kansas City, Kansas, United States, 66160
Status
Study Complete
Location
GSK Investigational Site
Minneapolis, Minnesota, United States, 55455
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10032
Status
Study Complete
Location
GSK Investigational Site
Portland, Oregon, United States, 97239
Status
Study Complete
Location
GSK Investigational Site
Sacramento, California, United States, 95817
Status
Study Complete
Location
GSK Investigational Site
St. Louis, Missouri, United States, 63110
Status
Study Complete
Location
GSK Investigational Site
Stanford, California, United States, 94305
Status
Study Complete
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2013-21-05
Actual study completion date
2013-04-11
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
Participate in clinical trial
Access to clinical trial data by researchers
Visit website