Last updated: 07/17/2024 15:37:14
Phase II doubleblind exploratory study of GSK2402968 in ambulant subjects with Duchenne muscular dystrophy
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A phase II, double blind, exploratory, parallel-group, placebocontrolled clinical study to assess two dosing regimens of GSK2402968 for efficacy, safety, tolerability and pharmacokinetics in ambulant subjects with Duchenne muscular dystrophy
Trial description: The purpose of this study is to determine whether GSK2402968 given as a continuous dose and as an intermittent dose is effective and safe in the treatment of Duchenne muscular dystrophy.
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 6 Minute Walking Distance (6MWD) test assessed at Week 25
Timeframe: Baseline and at Week 25
Secondary outcomes:
Mean change from Baseline in Rise from Floor Time
Timeframe: Baseline and up to Week 49
Number of participants with shift from Baseline between grade 3 to 6 with Respect to Grading for Rise from Floor
Timeframe: Up to Week 49
Mean change from Baseline in 10 Meter Walk/Run Test
Timeframe: Baseline and up to Week 49
Number of participants with shifts from Baseline with Respect to Grading for 10 Meter Walk/Run Grading
Timeframe: Up to Week 49
Mean change from Baseline in 4 Stair Climb - Ascent and Descent Time
Timeframe: Baseline and up to Week 49
Number of participants with shifts from Baseline with Respect to Grading for 4 Stair Climb - Ascent and Descend Grading
Timeframe: Up to Week 49
Mean change from Baseline in Muscle Strength Total Score
Timeframe: Baseline and up to Week 49
Mean change from Baseline in North Star Ambulatory Assessment (NSAA) Total Score
Timeframe: Baseline and up to Week 49
Mean change from Baseline in Creatine Kinase (CK) Serum Concentration
Timeframe: Baseline and up to Week 49
Mean change from Baseline in forced vital capacity (FVC) and forced expiratory volume in the first second of exhalation (FEV1)
Timeframe: Baseline and up to Week 49
Mean change from Baseline in predicted normal FVC and predicted normal FEV1
Timeframe: Baseline and up to Week 49
Mean change from Baseline in maximum expiratory pressure (MEP) and maximum inspiratory pressure (MIP)
Timeframe: Baseline and up to Week 49
Mean change from Baseline in peak expiratory flow (PEF) rate and peak cough flow (PCF)
Timeframe: Baseline and up to Week 49
Median time to loss of ambulation
Timeframe: Up to Week 49
Number of Participants with Change in Dystrophin Expression
Timeframe: Up to week 25
Number of Accidental Falls during 6MWD Assessment
Timeframe: Up to Week 49
Number of participants with adverse events (AEs) and Serious AEs (SAEs)
Timeframe: Up to Week 69
Number of participants with AEs by maximum intensity
Timeframe: Up to Week 69
Mean change from Baseline in height at Week 49
Timeframe: Baseline and Week 49
Mean change from Baseline in weight at Week 49
Timeframe: Baseline and Week 49
Mean change from Baseline in body mass index (BMI) at Week 49
Timeframe: Baseline and Week 49
Mean reaction size of participant's maximum injection site
Timeframe: Up to Week 49
Number of participants with Systolic and diastolic blood pressure (BP) of potential clinical concern (PCC) at any visit post Baseline
Timeframe: Up to Week 49
Number of participants with change from Baseline values of systolic and diastolic BP of PCC at any visit post Baseline.
Timeframe: Up to Week 49
Number of participants with heart rate of PCC at any visit post Baseline
Timeframe: Up to Week 49
Number of participants with change from Baseline values of PCC for heart rate at any visit post Baseline
Timeframe: Up to Week 49
Number of participants with abnormal clinically significant electrocardiogram (ECG) findings at Week 49
Timeframe: Week 49
Number of participants with PCC hematology data outside the reference range at any visit post Baseline
Timeframe: Up to Week 49
Number of participants with PCC clinical chemistry data outside the reference range at any visit post Baseline
Timeframe: Up to Week 49
Number of participants with PCC activated partial thromboplastin time (aPTT) time outside the reference range at any visit post Baseline
Timeframe: Up to Week 49
Number of participants with abnormal cystatin C at any visit post Baseline
Timeframe: Up to Week 49
Number of participants with abnormal Complement component 3 at any visit post Baseline
Timeframe: Up to Week 49
Number of participants with abnormal haptoglobulin
Timeframe: Up to Week 49
Number of participants with abnormal fibrinogen
Timeframe: Up to Week 49
Number of participants with abnormal C-reactive protein (CRP)
Timeframe: Up to Week 49
Number of participants with abnormal quantitative urinalysis data at any visit post-Baseline
Timeframe: Up to Week 49
Change from Baseline in urine cystatin C value at Week 49
Timeframe: Baseline and Week 49
Change from Baseline in Urine Kidney Injury Molecule 1 (KIM 1) at Week 49
Timeframe: Baseline and Week 49
Number of participants with abnormal echocardiogram values at any visit post Baseline
Timeframe: Baseline and up to Week 49
Area under concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration [AUC (0-t)] and 24 hours post dose [AUC (0-24)] at Week 29
Timeframe: Pre-dose, 0.5, 2, 4, 9, 12 and 24 hours postdose at Week 29 and between 48 and 60 hours post-dose
The observed maximum plasma concentration (Cmax) at Week 29
Timeframe: Pre-dose, 0.5, 2, 4, 9, 12 and 24 hours postdose at Week 49 and between 48 and 60 hours post-dose
Time of the observed maximum plasma concentration (tmax) at Week 29
Timeframe: Pre-dose, 0.5, 2, 4, 9, 12 and 24 hours postdose at Week 29 and between 48 and 60 hours post-dose
Number of participants with pharmacogenetic analysis.
Timeframe: Day 1
Interventions:
Drug: GSK2402968
Drug: matched placebo
Enrollment:
53
Observational study model:
Not applicable
Primary completion date:
2012-28-03
Time perspective:
Not applicable
Clinical publications:
T. Voit, H Topaloglu, V. Straub, F Muntoni, N Deconinck, M Guglieri, L Servais, V Ricotti, C Wardell, K Rolfe, S Hood, J Nakielny, N Quarcoo, P Wright, L Liefaard, A Morgan, G Campion, A Lourbakos, S DeKimpe, M Eagle, R Wilson, J Kraus.Exon skipping with drisapersen in Duchenne muscular dystrophy: clinical efficacy and safety results from a randomized, placebo-controlled Phase II study.Lancet Neurol.2014;13(10):987-996
Medical condition
Muscular Dystrophies
Product
drisapersen
Collaborators
Not applicable
Study date(s)
September 2010 to September 2012
Type
Interventional
Phase
2
Participation criteria
Sex
Male
Age
5+ years
Accepts healthy volunteers
No
- Ambulant subjects with Duchenne muscular dystrophy resulting from a mutation
- in the DMD gene, confirmed by a state-of-the-art DNA diagnostic technique
- any additional missing exon for DMD
- Current of history of liver or renal disease or impairment
Inclusion and exclusion criteria
Inclusion criteria:
- Ambulant subjects with Duchenne muscular dystrophy resulting from a mutation in 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) or H-RMCA (High-Resolution Melting Curve Analysis), and correctable by GSK2402968-induced DMD exon 51 skipping,
- Males, at least 5 years of age and with a life expectancy of at least 1 year
- Able to rise from floor in ≤7 seconds (without aids/orthoses),
- Able to complete the 6MWD test with a distance of at least 75m
- 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
- QTc <450msec
- On adequate contraception
- Able to comply with and complete all protocol requirements
Exclusion criteria:
- any additional missing exon for DMD
- Current of history of liver or renal disease or impairment
- Acute illness within 4 weeks of the first dose
- Use of prohibited meds within 6 months of fist dose
- Current participation in any other investigational clinical trial
- Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test at screening
- Symptomatic cardiomyopathy
- Children in Care
Trial location(s)
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45122
Status
Study Complete
Location
GSK Investigational Site
Freiburg, Baden-Wuerttemberg, Germany, 79106
Status
Study Complete
Location
GSK Investigational Site
Newcastle upon Tyne, United Kingdom, NE1 3BZ
Status
Study Complete
Location
GSK Investigational Site
WEstmead, New South Wales, Australia, 2145
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
2012-28-03
Actual study completion date
2012-12-09
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
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