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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.
Boys with Duchenne Muscular Dystrophy (DMD) suffer from a relentless, progressive and fatal disease due to lack of dystrophin, a critical muscle protein. There is currently no known cure for the disease. GSK2402968 is thought to correct several genetic mutations through skipping of exon 51 and therefore targets only those boys with these mutations.
A reasonable hypothesis is that increasing dystrophin will result in clinical improvement, and that the amount of dystrophin expressed will correlate with clinical improvement above a threshold level (e.g. around 30% of control). The initial limited efficacy data from completed and ongoing unblinded studies with GSK2402968 are encouraging as they have demonstrated de novo production of dystrophin and improved walking ability (primary efficacy endpoint) after 48 weeks of treatment which has been generally well tolerated.
This study is designed to explore the efficacy, safety and pharmacokinetics of two doses of GSK2402968 given over 24 weeks. The two doses to be assessed are 6mg/kg/week and 3mg/kg/week. Based on pharmacokinetic and pharmacodynamic modeling, it is predicted at steady-state that the 6 mg/kg/week dose will induce dystrophin expression greater than 30% of control. The 3 mg/kg/week dose was chosen as modeling predicts 3 mg/kg/week of GSK2402968 will produce dystrophin expression in the range of 18-22%. Potential variability between subjects could theoretically produce higher expression and lead to a dystrophin level correlated with clinical improvement.
Following the treatment period, the study has a 24 week post-treatment phase. The purpose of the post-treatment phase is to model the half-life of dystrophin, assess maintenance of response, and provide information about resolution of adverse event and laboratory abnormalities following cessation of treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GSK2402968 3 mg/kg/week | Experimental | 3 mg/kg/week of investigational product |
|
| GSK2402968 6 mg/kg/week | Experimental | 6 mg/kg/week of investigational Product |
|
| Placebo to match GSK2402968 3 mg/kg/week | Experimental | Placebo |
|
| Placebo to match GSK2402968 6 mg/kg/week | Experimental | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2402968 3mg/kg/week | Drug | Comparison of 2 doses of GSK2402968 |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in Muscle Function Using the 6 Minute Walking Distance | The participants during this assessment were asked to walk, at their own preferred speed, up and down a fixed distance until they were told to stop after 6 minutes. The participants were warned of the time and were told to stop earlier if they feel unable to continue. The total distance walked within the duration of 6 minutes (or until the participant stopped in case of early termination of the test), was recorded in meters. Change from Baseline, was defined as the post-randomization value minus the Baseline value. Baseline was defined as Week 0. | Baseline (Week 0) and Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Rise From Floor Time at Week 24 | The rise from floor was assessed, when the participants stood from a standardized supine position as quickly as possible when told to go. Time was recorded with a stopwatch from the initiation of movement until the assumption of upright standing. No aids or orthoses were allowed. Change from Baseline, was defined as the post-randomization value minus the Baseline value. Baseline was defined as Week 0. |
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Inclusion Criteria:
Exclusion Criteria:
Any additional missing exon for DMD that cannot be treated with GSK2402968,
Current or history of liver disease or impairment including :
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
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Sacramento | California | 95817 | United States | ||
| GSK Investigational Site |
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A total of 51 male participants, with Duchenne Muscular Dystrophy were randomized in the study. The study was conducted from 26 October 2011 to 04 November 2013.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo (Combined) | The participants in this arm were administered matching placebo subcutaneously for 24 Weeks. It was provided as 3 milliliter (mL) vials containing 1 mL sterile solution. |
| FG001 | GSK2402968 3 mg/kg/Week |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| GSK2402968 6 mg/kg/week |
| Drug |
Comparison of 2 doses of GSK2402968 |
|
| Placebo to match GSK2402968 3 mg/kg/week | Drug | Matched placebo |
|
| Placebo to match GSK2402968 6 mg/kg/week | Drug | Matched Placebo |
|
| Baseline (Week 0) and Week 24 |
| Change From Baseline in 4 Stair Climb Ascent/Descent Time at Week 24 | During this assessment, the participants were asked to ascend and descend four steps. The time for this was recorded with a stopwatch from the initiation of movement until the participant stands on the fourth step, (going up and going down separately). A flight of steps with handrail were used for this test. Change from Baseline, was defined as the post-randomization value minus the Baseline value. Baseline was defined as Week 0. | Baseline (Week 0) and Week 24 |
| Change From Baseline in 10 Meter Walk/Run at Week 24 | The participants during this assessment were asked to traverse marked 10-meter measured walkway as quickly as he safely can. Time was recorded to one tenth of a second with a stop watch from when his first foot crossed the start line until when the second foot crossed the finish line. How often the participant , touched the wall was to be noted. Care was taken to ensure that the participants were safe when completing this test. The assessor was allowed to walk nearby to provide 'emergency' help if needed, but must not support or provide manual assistance for the participant in any way. If the participant was unable to complete the 10-meter walk, the total distance was recorded. The participants were to perform the test in bare feet. No aids or orthoses were allowed. Change from Baseline, was defined as the post-randomization value minus the Baseline value. Baseline was defined as Week 0. | Baseline (Week 0) and Week 24 |
| Change From Baseline in Muscle Strength Total Score at Week 24 | The muscle strength was recorded by handheld myometry using a microFET2 myometer. Upper and lower limb proximal muscles were evaluated including knee flexors, knee extensors, elbow flexors, elbow extensors, shoulder abductors and hip flexors. Total score was calculated by summing up all individual scores. If data for any of the individual muscle strength tests was missing, the total score were set to missing for that visit. Change from Baseline, was defined as the post-randomization value minus the Baseline value. Baseline was defined as Week 0. | 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 | The muscle strength was recorded by handheld myometry using a microFET2 myometer. Upper and lower limb proximal muscles were evaluated including knee flexors, knee extensors, elbow flexors, elbow extensors, shoulder abductors and hip flexors. Change from Baseline, was defined as the post-randomization value minus the Baseline value. Baseline was defined as Week 0. | Baseline (Week 0) and Week 24 |
| Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score | The NSAA was a functional scale devised from Hammersmith Scale of Motor Ability specifically for use in ambulant children with DMD. It consists of 17 activities graded 0 (unable to perform), 1 (performs with modifications), 2 (normal movement). The scale assessed activities that required for ambulatory activity and included items that were rarely achieved in untreated DMD (jump, hop, raise head) as well as items that are known to progressively deteriorate over time (stand from a chair, walk). A standardized manual is available within the SPM with specific instructions for grading. Video snaps used in training program to ensure evaluator reliability. The total score ranged from 0-34 where the highest score of 34 implies absence of symptoms and lower score implies more severe symptoms. Change from Baseline, was defined as the post-randomization value minus the baseline value. Baseline was defined as Week 0. | Baselie (Week 0) and Week 24 |
| Number of Participants With Accidental Falls During 6 Minute Walk Distance Test | The participants during the 6 minute walk distance were asked to walk, at their own preferred speed, up and down a fixed distance until they were told to stop after 6 minutes. The participants were warned of the time and were told to stop earlier if they feel unable to continue. The total distance walked within the duration of 6 minutes (or until the participant stopped in case of early termination of the test), was recorded in metersThe number of accident falls during the 6 minute walk distance were reported. Data is reported for the number of participants with accidental falls of 0, 1 and 2. | Baseline (Week 0), Week 24, Week 36 and Week 48 |
| Change From Baseline in Creatinine Kinase Serum Concentrations | Creatine kinase (CK) is a muscle-specific enzyme; its level in plasma is considered to reflect the extent of muscle damage. In the blood samples drawn to this purpose, the plasma level of CK was measured. Change from Baseline, was defined as the post-randomization value minus the baseline value. Baseline was defined as Week 0. | Baseline (Week 0) and Week 48 |
| Change From Baseline in Forced Expiratory Volume in the First Second of Exhalation (FEV1) at Week 24 | FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from Baseline, was defined as the post-randomization value minus the Baseline value. Baseline was defined as Week 0. | Baseline (Week 0) and Week 24 |
| Change From Baseline in Forced Vital Capacity (FVC) at Week 24 | FVC is defined as the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Change from Baseline, was defined as the post-randomization value minus the baseline value. Baseline was defined as Week 0. | Baseline (Week 0) and Week 24 |
| Change From Baseline in Peak Cough Flow at Week 24 | The peak cough flow was conducted using a spirometer. Change from Baseline, was defined as the post-randomization value minus the Baseline value. Baseline was defined as Week 0. | Baseline (Week 0) and Week 24 |
| Change From Baseline in Peak Expiratory Flow at Week 24 | The peak expiratory flow is a measure of the amount of air that can be pushed through the airways in a single rapid exhalation. The peak expiratory flow was measured using spirometry. Change from Baseline, was defined as the post-randomization value minus the baseline value. Baseline was defined as Week 0. | Baseline (Week 0) and Week 24 |
| Change From Baseline in Sniff Pressure Test at Week 24 | This was one of the pulmonary function test which was a non-invasive procedure. It measured the inspiratory muscle strength by transdiaphragmatic (Pdi) and esophageal pressures (Pes) generated during volitional and nonvolitional maneuvers. Change from Baseline, was defined as the post-randomization value minus the baseline value. Baseline was defined as Week 0. | Baseline (Week 0) and Week 24 |
| Number of Participants With Change From Baseline in Dystrophin Expression at Week 24 by Immunofluorescence Assay (IFA) | A muscle biopsy from the tibialis anterior muscle was taken to assess the expression of dystrophin. The muscle biopsy samples were collected by open biopsy or with the conchotome method according to standard hospital procedures for obtaining muscle biopsies from children. The minimum amount of muscle tissue required is a small piece of muscle of at least 0.5 x 0.5 x 0.5 centimeters. The muscle tissue was immediately frozen in liquid nitrogen-cooled 2-methylbutane and stored at -80°Celsius (C) or -70°C till shipment. In case of DMD participants , there is defect in the dystrophin producing gene or absence. Data for number of participants with change from baseline in dystrophin expression, was diagnosed using IFA and was categorized as strong increase, increase, and no change, decrease. | Baseline (Week 0) and Week 24 |
| Number of Clinician Global Impression of Improvement (CGI-I) Responders | Single item question designed to provide a brief, stand-alone assessment of the clinician's view of the participant's global functioning after initiating a study medication, compared to their global functioning just prior to initiating treatment. Evaluated by an expert physician or evaluator familiar with DMD and who could make an expert clinical global judgement about severity of illness across various time points within context of clinical experience. The CGI-I reflects the clinician's judgment about the total picture of the participant : the illness severity, the level of distress and other aspects of impairment, and impact of illness on functioning. The CGI-I is rated without regard to clinician's belief that any clinical changes are or are not due to medication and without consideration of etiology of symptoms. It is measured on 7-point Likert scale (1 = 'very much improved', 2 = 'much improved', 4 = 'no change', 5 = 'minimally worse', 6 = 'much worse', 7 = 'very much worse'). | Week 24 and Week 48 |
| Assessment of Functional Outcome by : Functional Outcomes Survey During Treatment Period | This was conducted by the family or caregiver. This helped to document the observed changes in the participant's functional outcome like the day to day activities; general health, mobility, and other general daily activities. The data for Week 24 has been reported as improved, not improved and not applicable. | Up to Week 24 |
| Assessment of Functional Outcome by : Physician Assessment of Daily Living | This was conducted by the physician, which helped to assess and document observed changes in the participant by the physician reported by the participant or his family or caregiver. This was reported as any worsening and any improvement up to week 24. | Week 24 and Week 48 |
| Stanford |
| California |
| 94305 |
| United States |
| GSK Investigational Site | Gulf Breeze | Florida | 32561 | United States |
| GSK Investigational Site | Iowa City | Iowa | 52242 | United States |
| GSK Investigational Site | Kansas City | Kansas | 66160 | United States |
| GSK Investigational Site | Baltimore | Maryland | 21205 | United States |
| GSK Investigational Site | Minneapolis | Minnesota | 55455 | United States |
| GSK Investigational Site | St Louis | Missouri | 63110 | United States |
| GSK Investigational Site | New York | New York | 10032 | United States |
| GSK Investigational Site | Durham | North Carolina | 27710 | United States |
| GSK Investigational Site | Cincinnati | Ohio | 45229 | United States |
| GSK Investigational Site | Columbus | Ohio | 43205 | United States |
| GSK Investigational Site | Portland | Oregon | 97239 | United States |
| GSK Investigational Site | Dallas | Texas | 75207 | United States |
The participants in this arm were administered with 3 milligram (mg) per kilogram (kg) GSK2402968, subcutaneously for 24 weeks. It was provided as 3 mL vials containing 1 mL sterile solution. The concentration of drisapersen solution was 200 mg/mL
| FG002 | GSK2402968 6 mg/kg/Week | The participants in this arm were administered with 6 mg per kg GSK2402968, subcutaneously for 24 weeks. It was provided as 3 mL vials containing 1 mL sterile solution. The concentration of drisapersen solution was 200 mg/mL |
| COMPLETED |
|
| NOT COMPLETED |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo (Combined) | The participants in this arm were administered matching placebo subcutaneously for 24 Weeks. It was provided as 3 mL vials containing 1 mL sterile solution. |
| BG001 | GSK2402968 3 mg/kg/Week | The participants in this arm were administered with 3 mg per kilogram kg GSK2402968, subcutaneously for 24 weeks. It was provided as 3 mL vials containing 1 mL sterile solution. The concentration of drisapersen solution was 200 mg/mL. |
| BG002 | GSK2402968 6 mg/kg/Week | The participants in this arm were administered with 6 mg per kg GSK2402968, subcutaneously for 24 weeks. It was provided as 3 mL vials containing 1 mL sterile solution. The concentration of drisapersen solution was 200 mg/mL. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Mean Change From Baseline in Muscle Function Using the 6 Minute Walking Distance | The participants during this assessment were asked to walk, at their own preferred speed, up and down a fixed distance until they were told to stop after 6 minutes. The participants were warned of the time and were told to stop earlier if they feel unable to continue. The total distance walked within the duration of 6 minutes (or until the participant stopped in case of early termination of the test), was recorded in meters. Change from Baseline, was defined as the post-randomization value minus the Baseline value. Baseline was defined as Week 0. | Intent to Treat (ITT) Population was defined as all participants who were randomized to the study, received at least one dose of study medication and have at least one post-Baseline efficacy assessment | Posted | Least Squares Mean | Standard Error | Meters | Baseline (Week 0) and Week 24 |
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| Secondary | Change From Baseline in Rise From Floor Time at Week 24 | The rise from floor was assessed, when the participants stood from a standardized supine position as quickly as possible when told to go. Time was recorded with a stopwatch from the initiation of movement until the assumption of upright standing. No aids or orthoses were allowed. Change from Baseline, was defined as the post-randomization value minus the Baseline value. Baseline was defined as Week 0. | ITT Population | Posted | Least Squares Mean | Standard Error | Seconds | Baseline (Week 0) and Week 24 |
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| Secondary | Change From Baseline in 4 Stair Climb Ascent/Descent Time at Week 24 | During this assessment, the participants were asked to ascend and descend four steps. The time for this was recorded with a stopwatch from the initiation of movement until the participant stands on the fourth step, (going up and going down separately). A flight of steps with handrail were used for this test. Change from Baseline, was defined as the post-randomization value minus the Baseline value. Baseline was defined as Week 0. | ITT Population | Posted | Least Squares Mean | Standard Error | seconds | Baseline (Week 0) and Week 24 |
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| Secondary | Change From Baseline in 10 Meter Walk/Run at Week 24 | The participants during this assessment were asked to traverse marked 10-meter measured walkway as quickly as he safely can. Time was recorded to one tenth of a second with a stop watch from when his first foot crossed the start line until when the second foot crossed the finish line. How often the participant , touched the wall was to be noted. Care was taken to ensure that the participants were safe when completing this test. The assessor was allowed to walk nearby to provide 'emergency' help if needed, but must not support or provide manual assistance for the participant in any way. If the participant was unable to complete the 10-meter walk, the total distance was recorded. The participants were to perform the test in bare feet. No aids or orthoses were allowed. Change from Baseline, was defined as the post-randomization value minus the Baseline value. Baseline was defined as Week 0. | ITT population. | Posted | Least Squares Mean | Standard Error | Seconds | Baseline (Week 0) and Week 24 |
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| Secondary | Change From Baseline in Muscle Strength Total Score at Week 24 | The muscle strength was recorded by handheld myometry using a microFET2 myometer. Upper and lower limb proximal muscles were evaluated including knee flexors, knee extensors, elbow flexors, elbow extensors, shoulder abductors and hip flexors. Total score was calculated by summing up all individual scores. If data for any of the individual muscle strength tests was missing, the total score were set to missing for that visit. Change from Baseline, was defined as the post-randomization value minus the Baseline value. Baseline was defined as Week 0. | ITT Population. Only those participants available at the specified timepoints were analyzed | Posted | Least Squares Mean | Standard Error | Pounds (lbs) | Baseline (Week 0) and Week 24 |
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| Secondary | Change From Baseline in Muscle Strength Tests For-Knee Extensor, Knee Flexor, Hip Flexor, Elbow Flexor, Elbow Extensor, Shoulder Abductor at Week 24 | The muscle strength was recorded by handheld myometry using a microFET2 myometer. Upper and lower limb proximal muscles were evaluated including knee flexors, knee extensors, elbow flexors, elbow extensors, shoulder abductors and hip flexors. Change from Baseline, was defined as the post-randomization value minus the Baseline value. Baseline was defined as Week 0. | ITT population. | Posted | Mean | Standard Deviation | lbs | Baseline (Week 0) and Week 24 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score | The NSAA was a functional scale devised from Hammersmith Scale of Motor Ability specifically for use in ambulant children with DMD. It consists of 17 activities graded 0 (unable to perform), 1 (performs with modifications), 2 (normal movement). The scale assessed activities that required for ambulatory activity and included items that were rarely achieved in untreated DMD (jump, hop, raise head) as well as items that are known to progressively deteriorate over time (stand from a chair, walk). A standardized manual is available within the SPM with specific instructions for grading. Video snaps used in training program to ensure evaluator reliability. The total score ranged from 0-34 where the highest score of 34 implies absence of symptoms and lower score implies more severe symptoms. Change from Baseline, was defined as the post-randomization value minus the baseline value. Baseline was defined as Week 0. | ITT Population | Posted | Least Squares Mean | Standard Error | Scores on scale | Baselie (Week 0) and Week 24 |
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| Secondary | Number of Participants With Accidental Falls During 6 Minute Walk Distance Test | The participants during the 6 minute walk distance were asked to walk, at their own preferred speed, up and down a fixed distance until they were told to stop after 6 minutes. The participants were warned of the time and were told to stop earlier if they feel unable to continue. The total distance walked within the duration of 6 minutes (or until the participant stopped in case of early termination of the test), was recorded in metersThe number of accident falls during the 6 minute walk distance were reported. Data is reported for the number of participants with accidental falls of 0, 1 and 2. | ITT Population. Only those participants available at the specified timepoints were analyzed | Posted | Number | Participants | Baseline (Week 0), Week 24, Week 36 and Week 48 |
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| Secondary | Change From Baseline in Creatinine Kinase Serum Concentrations | Creatine kinase (CK) is a muscle-specific enzyme; its level in plasma is considered to reflect the extent of muscle damage. In the blood samples drawn to this purpose, the plasma level of CK was measured. Change from Baseline, was defined as the post-randomization value minus the baseline value. Baseline was defined as Week 0. | ITT population. Only those participants available at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | International units per liter | Baseline (Week 0) and Week 48 |
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| Secondary | Change From Baseline in Forced Expiratory Volume in the First Second of Exhalation (FEV1) at Week 24 | FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from Baseline, was defined as the post-randomization value minus the Baseline value. Baseline was defined as Week 0. | ITT Population. Only those participants available at the indicated timepoints were used for analysis | Posted | Mean | Standard Deviation | Litres | Baseline (Week 0) and Week 24 |
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| Secondary | Change From Baseline in Forced Vital Capacity (FVC) at Week 24 | FVC is defined as the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Change from Baseline, was defined as the post-randomization value minus the baseline value. Baseline was defined as Week 0. | ITT population. Only those participants available at the indicated timepoints were used for analysis. | Posted | Mean | Standard Deviation | Litres | Baseline (Week 0) and Week 24 |
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| Secondary | Change From Baseline in Peak Cough Flow at Week 24 | The peak cough flow was conducted using a spirometer. Change from Baseline, was defined as the post-randomization value minus the Baseline value. Baseline was defined as Week 0. | ITT population. Only those participants available at the indicated timepoints were used for analysis | Posted | Mean | Standard Deviation | Litres per minute | Baseline (Week 0) and Week 24 |
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| Secondary | Change From Baseline in Peak Expiratory Flow at Week 24 | The peak expiratory flow is a measure of the amount of air that can be pushed through the airways in a single rapid exhalation. The peak expiratory flow was measured using spirometry. Change from Baseline, was defined as the post-randomization value minus the baseline value. Baseline was defined as Week 0. | ITT population. Only those participants available at the specified time points were analyzed | Posted | Mean | Standard Deviation | Litres per minute | Baseline (Week 0) and Week 24 |
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| Secondary | Change From Baseline in Sniff Pressure Test at Week 24 | This was one of the pulmonary function test which was a non-invasive procedure. It measured the inspiratory muscle strength by transdiaphragmatic (Pdi) and esophageal pressures (Pes) generated during volitional and nonvolitional maneuvers. Change from Baseline, was defined as the post-randomization value minus the baseline value. Baseline was defined as Week 0. | ITT Population. Only those participants available at the specified time points were analyzed | Posted | Mean | Standard Deviation | Centimeter of water | Baseline (Week 0) and Week 24 |
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| Secondary | Number of Participants With Change From Baseline in Dystrophin Expression at Week 24 by Immunofluorescence Assay (IFA) | A muscle biopsy from the tibialis anterior muscle was taken to assess the expression of dystrophin. The muscle biopsy samples were collected by open biopsy or with the conchotome method according to standard hospital procedures for obtaining muscle biopsies from children. The minimum amount of muscle tissue required is a small piece of muscle of at least 0.5 x 0.5 x 0.5 centimeters. The muscle tissue was immediately frozen in liquid nitrogen-cooled 2-methylbutane and stored at -80°Celsius (C) or -70°C till shipment. In case of DMD participants , there is defect in the dystrophin producing gene or absence. Data for number of participants with change from baseline in dystrophin expression, was diagnosed using IFA and was categorized as strong increase, increase, and no change, decrease. | ITT population. Only those participants available at the specified timepoints were analyzed. | Posted | Count of Participants | Participants | Baseline (Week 0) and Week 24 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Clinician Global Impression of Improvement (CGI-I) Responders | Single item question designed to provide a brief, stand-alone assessment of the clinician's view of the participant's global functioning after initiating a study medication, compared to their global functioning just prior to initiating treatment. Evaluated by an expert physician or evaluator familiar with DMD and who could make an expert clinical global judgement about severity of illness across various time points within context of clinical experience. The CGI-I reflects the clinician's judgment about the total picture of the participant : the illness severity, the level of distress and other aspects of impairment, and impact of illness on functioning. The CGI-I is rated without regard to clinician's belief that any clinical changes are or are not due to medication and without consideration of etiology of symptoms. It is measured on 7-point Likert scale (1 = 'very much improved', 2 = 'much improved', 4 = 'no change', 5 = 'minimally worse', 6 = 'much worse', 7 = 'very much worse'). | ITT population. Only those participants available at the specified time points were analyzed. | Posted | Count of Participants | Participants | Week 24 and Week 48 |
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| Secondary | Assessment of Functional Outcome by : Functional Outcomes Survey During Treatment Period | This was conducted by the family or caregiver. This helped to document the observed changes in the participant's functional outcome like the day to day activities; general health, mobility, and other general daily activities. The data for Week 24 has been reported as improved, not improved and not applicable. | ITT population. Only those participants available at that particular time points were analyzed. | Posted | Count of Participants | Participants | Up to Week 24 |
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| Secondary | Assessment of Functional Outcome by : Physician Assessment of Daily Living | This was conducted by the physician, which helped to assess and document observed changes in the participant by the physician reported by the participant or his family or caregiver. This was reported as any worsening and any improvement up to week 24. | ITT population. Only those participants available at the specified time points were analyzed. | Posted | Count of Participants | Participants | Week 24 and Week 48 |
|
Up to Week 48
Safety Population was defined as all participants who received at least one dose of study medication.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo (Combined) | The participants in this arm were administered matching placebo subcutaneously for 24 Weeks. It was provided as 3 mL vials containing 1 mL sterile solution | 0 | 16 | 1 | 16 | 13 | 16 |
| EG001 | GSK2402968 3 mg/kg/Week | The participants in this arm were administered with 3 mg per kg GSK2402968, subcutaneously for 24 weeks. It was provided as 3 mL vials containing 1 mL sterile solution. The concentration of drisapersen solution was 200 mg/mL | 0 | 17 | 0 | 17 | 16 | 17 |
| EG002 | GSK2402968 6 mg/kg/Week | The participants in this arm were administered with 6 mg per kg GSK2402968, subcutaneously for 24 weeks. It was provided as 3 mL vials containing 1 mL sterile solution. The concentration of drisapersen solution was 200 mg/mL | 0 | 18 | 0 | 18 | 17 | 18 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Wound infection staphylococcal | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection site erythema | General disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Injection site discolouration | General disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Injection site bruising | General disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Chromaturia | Renal and urinary disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Injection site pruritus | General disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
| |
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
| |
| Otitis media | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 16.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
| |
| Injection site haematoma | General disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Injection site swelling | General disorders | MedDRA 16.1 | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA 16.1 | Systematic Assessment |
| |
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Postoperative wound complication | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
| |
| Protein urine present | Investigations | MedDRA 16.1 | Systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Vessel puncture site bruise | General disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Abnormal behaviour | Psychiatric disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Activated partial thromboplastin time prolonged | Investigations | MedDRA 16.1 | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Application site bruise | General disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 16.1 | Systematic Assessment |
| |
| Autism spectrum disorder | Psychiatric disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Balance disorder | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Blood fibrinogen decreased | Investigations | MedDRA 16.1 | Systematic Assessment |
| |
| Blood immunoglobulin G decreased | Investigations | MedDRA 16.1 | Systematic Assessment |
| |
| Burning sensation | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Conjunctivitis | Eye disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Creatinine renal clearance decreased | Investigations | MedDRA 16.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 16.1 | Systematic Assessment |
| |
| ECG signs of ventricular hypertrophy | Investigations | MedDRA 16.1 | Systematic Assessment |
| |
| Ear infection | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 16.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Excoriation | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
| |
| Fibrin D dimer increased | Investigations | MedDRA 16.1 | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Food poisoning | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Hand fracture | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Infusion site haematoma | General disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Injection site haemorrhage | General disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Injection site oedema | General disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Injection site reaction | General disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Laceration | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
| |
| Lip swelling | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Muscle hypertrophy | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Obesity | Metabolism and nutrition disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Onychomadesis | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
| |
| Pharyngitis streptococcal | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
| |
| Post procedural discomfort | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
| |
| Pulmonary congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Red blood cells urine | Investigations | MedDRA 16.1 | Systematic Assessment |
| |
| Reticulocyte count increased | Investigations | MedDRA 16.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
| |
| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Sleep disorder | Psychiatric disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Stitch abscess | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
| |
| Systolic dysfunction | Cardiac disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Thermal burn | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Tongue biting | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Tongue disorder | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Upper respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Urine analysis abnormal | Investigations | MedDRA 16.1 | Systematic Assessment |
| |
| Vessel puncture site pain | General disorders | MedDRA 16.1 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
| |
| Vitamin D decreased | Investigations | MedDRA 16.1 | Systematic Assessment |
| |
| Wrist fracture | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
| ID | Term |
|---|---|
| D009136 | Muscular Dystrophies |
| D020388 | Muscular Dystrophy, Duchenne |
| ID | Term |
|---|---|
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D040181 | Genetic Diseases, X-Linked |
Not provided
Not provided
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Treatment difference: Placebo Vs GSK2402968 6 mg | Mixed Model Repeated Measures | Model included terms for treatment, visit, treatment by visit, centre grouping, baseline and baseline by visit | 0.069 | Due to the two comparisons for the two different doses, the type 1 error rate (5% overall) was preserved by utilising a hierarchical approach, testing the 6mg/kg GSK2402968 dose first | Mean Difference (Net) | 27.099 | 2-Sided | 95 | -2.210 | 56.408 | Superiority or Other |
|
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|
| OG002 | GSK2402968 6 mg/kg/Week | The participants in this arm were administered with 6 mg per kg GSK2402968, subcutaneously for 24 weeks. It was provided as 3 mL vials containing 1 mL sterile solution. The concentration of drisapersen solution was 200 mg/mL |
|
|
|
The participants in this arm were administered with 6 mg per kg GSK2402968, subcutaneously for 24 weeks. It was provided as 3 mL vials containing 1 mL sterile solution. The concentration of drisapersen solution was 200 mg/mL |
|
|
|
|
|
| OG002 | GSK2402968 6 mg/kg/Week | The participants in this arm were administered with 6 mg per kg GSK2402968, subcutaneously for 24 weeks. It was provided as 3 mL vials containing 1 mL sterile solution. The concentration of drisapersen solution was 200 mg per mL |
|
|
|
| GSK2402968 6 mg/kg/Week |
The participants in this arm were administered with 6 mg per kg GSK2402968, subcutaneously for 24 weeks. It was provided as 3 mL vials containing 1 mL sterile solution. The concentration of drisapersen solution was 200 mg per mL |
|
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| OG002 | GSK2402968 6 mg/kg/Week | The participants in this arm were administered with 6 mg per kg GSK2402968, subcutaneously for 24 weeks. It was provided as 3 mL vials containing 1 mL sterile solution. The concentration of drisapersen solution was 200 mg per mL |
|
|
The participants in this arm were administered with 3 mg per kilogram kg GSK2402968, subcutaneously for 24 weeks. It was provided as 3 mL vials containing 1 mL sterile solution. The concentration of drisapersen solution was 200 mg per mL
| OG002 | GSK2402968 6 mg/kg/Week | The participants in this arm were administered with 6 mg per kg GSK2402968, subcutaneously for 24 weeks. It was provided as 3 mL vials containing 1 mL sterile solution. The concentration of drisapersen solution was 200 mg per mL |
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