A Clinical Study to Assess the Efficacy and Safety of GSK2402968 in Subjects With Duchenne Muscular Dystrophy (DMD114044)

• ClinicalTrials.gov Identifier: NCT01254019
• Recruitment Status: Completed
• First Posted: December 6, 2010
• Results First Posted: January 28, 2019
• Last Update Posted: January 28, 2019
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Muscular Dystrophies
• Intervention: Drug: GSK2402968 6mg/kg/week
• Enrollment: 186

Participant Flow

Recruitment Details	This study was conducted across 44 centers in 19 countries from 02 December 2010 to 28 June 2013.
Pre-assignment Details	A total of 186 participants were randomized which included males with a maximum age of 16 years, no adults were included in this study.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 milligrams per kilogram per week (mg/kg/week) subcutaneous injection preferably in the morning over the 48 week treatment period.
Period Title: Overall Study
Started	61	125
Completed	60	121
Not Completed	1	4
Reason Not Completed
Adverse Event	0	2
Protocol Violation	1	0
Withdrawal by Subject	0	2

Baseline Characteristics

Arm/Group Title		Placebo	GSK2402968 6mg/kg/Week	Total
Arm/Group Description		Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.	Total of all reporting groups
Overall Number of Baseline Participants		61	125	186
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	61 participants	125 participants	186 participants
		8.0 (2.37)	8.3 (2.43)	8.2 (2.41)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	61 participants	125 participants	186 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	61 100.0%	125 100.0%	186 100.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	61 participants	125 participants	186 participants
African American/African Heritage		1 1.6%	0 0.0%	1 0.5%
Asian - Central/South Asian Heritage		1 1.6%	3 2.4%	4 2.2%
Asian - East Asian Heritage		3 4.9%	6 4.8%	9 4.8%
Asian - Japanese Heritage		5 8.2%	9 7.2%	14 7.5%
Asian - South East Asian Heritage		0 0.0%	2 1.6%	2 1.1%
White - Arabic/North African Heritage		4 6.6%	5 4.0%	9 4.8%
White - White/Caucasian/European Heritage		46 75.4%	95 76.0%	141 75.8%
White - Mixed Race		0 0.0%	1 0.8%	1 0.5%
Mixed Race		1 1.6%	4 3.2%	5 2.7%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Muscle Function Using the 6 Minute Walking Distance (6MWD) Test Assessed at Week 48
Description	During the 6MWD, participants 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 that they may stop earlier if they feel unable to continue. The total distance walked within 6 minutes (or until the participant stopped in case of early termination of the test), the 6MWD, was recorded in meters as well as any falls. Baseline was defined as participants randomization assessment at Visit 3 (Day 0). Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.
Time Frame	Baseline (Day 0) and Week 48

Outcome Measure Data

Analysis Population Description

The Intent-to-Treat (ITT) Population comprised all participants who received at least one dose of study medication and for whom at least one post-Baseline efficacy assessment was available. Only those participants available at the specified time point were analyzed.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed	59	117
Least Squares Mean (Standard Error); Unit of Measure: Meters
	-52.65 (10.423)	-42.32 (7.378)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK2402968 6mg/kg/Week
	Comments	GSK2402968 6mg/kg/week Vs Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.415
	Comments	Statistical significance was assessed at the 5% level.
	Method	Mixed Effect Model for Repeated Measures
	Comments	Model included terms for treatment, visit, treatment by visit, country grouping, Baseline and Baseline by visit.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	10.334
	Confidence Interval	(2-Sided) 95%; -14.645 to 35.312
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Change From Baseline in the Linearized North Star Ambulatory Assessment (NSAA) Total Score at Week 48
Description	The NSAA is a functional scale devised from the Hammersmith Scale of Motor Ability specifically for use in ambulant children with Duchenne muscular dystrophy (DMD). It consists of 17 activities graded 0 (unable to perform), 1 (performs with modifications), 2 (normal movement). The scale assesses activities required to remain functionally ambulant (e.g. rise from the floor), activities that can be difficult even early in the disease (e.g. standing on heels) and activities that are known to progressively deteriorate over time (stand from a chair, walk). NSAA total score was achieved by adding the responses of all activities, ranging from 0 to 34, with a score of 34 implying normal function and lower score implying more severe symptoms. Baseline was defined as participants randomization assessment at Visit 3 (Day 0). Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48. A positive change from Baseline indicated improvement.
Time Frame	Baseline (Day 0) and Week 48

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the indicated time point were analyzed.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed	58	117
Least Squares Mean (Standard Error); Unit of Measure: Scores on a scale
	-6.7 (1.43)	-7.2 (1.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK2402968 6mg/kg/Week
	Comments	GSK2402968 6mg/kg/week Vs Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.757
	Comments	Statistical significance (SS) was only to be assessed if a statistically significant difference was observed for the primary and any secondary endpoints higher in the pre-defined hierarchy. Hence conclusions with regards to SS should not be made.
	Method	Mixed Effect Model for Repeated Measures
	Comments	Model included terms for treatment, visit, treatment by visit, country grouping, Baseline and Baseline by visit.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.53
	Confidence Interval	(2-Sided) 95%; -3.95 to 2.88
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Change From Baseline in the 4 Stair Climb (Ascent) Velocity at Week 48
Description	The participant was asked to ascend four steps. Time was recorded with a stopwatch from the initiation of movement until the participant stood on the fourth step. A flight of steps with handrail was used for this test. Number of stairs ascended per second was calculated as 4 divided by the time to ascend 4 complete stairs. Baseline was defined as participants randomization assessment at Visit 3 (Day 0). Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.
Time Frame	Baseline (Day 0) and Week 48

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the indicated time point were analyzed.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed	55	111
Least Squares Mean (Standard Error); Unit of Measure: Stairs per second
	-0.12 (0.049)	-0.14 (0.035)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK2402968 6mg/kg/Week
	Comments	GSK2402968 6mg/kg/week Vs Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.718
	Comments	SS was only to be assessed if a statistically significant difference was observed for the primary and any secondary endpoints higher in the pre-defined hierarchy. Hence conclusions with regards to SS should not be made.
	Method	Mixed Effect Model for Repeated Measures
	Comments	Model included terms for treatment, visit, treatment by visit, country grouping, Baseline and Baseline by visit.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.021
	Confidence Interval	(2-Sided) 95%; -0.137 to 0.095
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Change From Baseline in the 10-meter Walk/Run Velocity at Week 48
Description	The participant was instructed to perform the test bare foot. No aids or orthoses were allowed. The participant was asked to traverse a marked 10-meter measured walkway as quickly as he safely could. 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. If the wall was touched, it was noted how often. Care was taken to ensure that the participant was safe when completing this test. The assessor walked nearby to provide emergency help if needed, but did not support or provide manual assistance to the participant in any way. If the participant could not complete the 10-meter walk, the total distance was recorded. 10 minute walk/run speed was equal to 10 divided by time taken to complete 10 minute walk/run. Baseline was defined as participants randomization assessment at Visit 3 (Day 0). Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.
Time Frame	Baseline (Day 0) and Week 48

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the indicated time point were analyzed.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed	58	117
Least Squares Mean (Standard Error); Unit of Measure: Meters per second
	-0.20 (0.050)	-0.21 (0.035)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK2402968 6mg/kg/Week
	Comments	GSK2402968 6mg/kg/week Vs Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.881
	Comments	SS was only to be assessed if a statistically significant difference was observed for the primary and any secondary endpoints higher in the pre-defined hierarchy. Hence conclusions with regards to SS should not be made.
	Method	Mixed Effect Model for Repeated Measures
	Comments	Model included terms for treatment, visit, treatment by visit, country grouping, Baseline and Baseline by visit.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.009
	Confidence Interval	(2-Sided) 95%; -0.129 to 0.111
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Change From Baseline in the Timed Function Test Rise From Floor at Week 48
Description	The participant 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 are allowed. Baseline was defined as participants randomization assessment at Visit 3 (Day 0). Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.
Time Frame	Baseline (Day 0) and Week 48

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the indicated time point were analyzed.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed	44	91
Least Squares Mean (Standard Error); Unit of Measure: Seconds
	7.48 (2.080)	6.36 (1.463)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK2402968 6mg/kg/Week
	Comments	GSK2402968 6mg/kg/week Vs Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.658
	Comments	No adjustment for multiplicity was made, so p-values should not be used to make conclusions with regards to statistical significance.
	Method	Mixed Effect Model for Repeated Measures
	Comments	Model included terms for treatment, visit, treatment by visit, country grouping, Baseline and Baseline by visit.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.115
	Confidence Interval	(2-Sided) 95%; -6.097 to 3.866
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Change From Baseline in the 4 Stair Climb (Descent) Velocity at Week 48
Description	The participant was asked to descend four steps. Time was recorded with a stopwatch from the initiation of movement until the participant stood on the fourth step. A flight of steps with handrail was used for this test. Number of stairs descended per second was calculated as 4 divided by the time to descend 4 complete stairs. Baseline was defined as participants randomization assessment at Visit 3 (Day 0). Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.
Time Frame	Baseline (Day 0) and Week 48

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the indicated time point were analyzed.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed	55	109
Least Squares Mean (Standard Error); Unit of Measure: Stairs per second
	-0.15 (0.052)	-0.11 (0.037)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK2402968 6mg/kg/Week
	Comments	GSK2402968 6mg/kg/week Vs Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.513
	Comments	No adjustment for multiplicity was made, so p-values should not be used to make conclusions with regards to statistical significance.
	Method	Mixed Effect Model for Repeated Measures
	Comments	Model included terms for treatment, visit, treatment by visit, country grouping, Baseline and Baseline by visit.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.041
	Confidence Interval	(2-Sided) 95%; -0.082 to 0.164
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Change From Baseline in Muscle Strength (Total Score) at Week 48
Description	Muscle strength was recorded by handheld myometry using a micro force evaluation testing 2 (FET2) myometer. Upper and lower limb proximal muscles were evaluated including knee flexors, knee extensors, elbow flexors, elbow extensors, shoulder abductors and hip flexors. The muscle strength total score (pounds) was the sum of the 12 individual muscle strength tests. Baseline was defined as participants randomization assessment at Visit 3 (Day 0). Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.
Time Frame	Baseline (Day 0) and Week 48

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the indicated time point were analyzed.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed	58	118
Least Squares Mean (Standard Error); Unit of Measure: Pounds
	-1.21 (2.729)	-2.18 (1.926)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK2402968 6mg/kg/Week
	Comments	GSK2402968 6mg/kg/week Vs Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.769
	Comments	No adjustment for multiplicity was made, so p-values should not be used to make conclusions with regards to statistical significance.
	Method	Mixed Effect Model for Repeated Measures
	Comments	Model included terms for treatment, visit, treatment by visit, country grouping, Baseline and Baseline by visit.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.965
	Confidence Interval	(2-Sided) 95%; -7.446 to 5.516
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Kaplan-Meier Estimates for Time to Loss of Ambulation
Description	All participants were ambulant when entered into the study; however they could have become non-ambulant at some time during the study. The date was recorded and the variable time to loss of ambulation was calculated as: time to loss of ambulation = date of loss of ambulation - date of first dose. Median and interquartile range i.e. 1st and 3rd quartile is presented.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT Population.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed	61	125
Median (Inter-Quartile Range); Unit of Measure: Days
	NA [1]; (NA to NA)	NA [2]; (390.0 to NA)

[1]

Median, upper limit and lower limit was not reached due to insufficient number of participants with events.

[2]

Median and upper limit was not reached due to insufficient number of participants with events.

9. Secondary Outcome

Title	Number of Participants Who Experienced Accidental Falls During 6MWD Assessments at Week 48
Description	The number of accidental falls occurring during the 6MWD were counted. Data has been presented for the number of participants who experienced accidental falls (from 0 to 1) during the 6MWD assessment.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the indicated time point were analyzed.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed	53	103
Measure Type: Count of Participants; Unit of Measure: Participants
Number of falls=0	48 90.6%	102 99.0%
Number of falls=1	5 9.4%	1 1.0%

10. Secondary Outcome

Title	Change From Baseline in Creatine Kinase Serum Concentrations at Week 48
Description	Creatine kinase is a muscle-specific enzyme; its level in serum is considered to reflect the extent of muscle damage. In the blood samples drawn to this purpose, the serum level of creatine kinase were measured. Baseline was defined as participants randomization assessment at Visit 3 (Day 0). Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.
Time Frame	Baseline (Day 0) and Week 48

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the indicated time point were analyzed.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo 1 mL sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed	60	118
Least Squares Mean (Standard Error); Unit of Measure: International units per liter
	-1228.5 (500.59)	-5273.5 (359.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK2402968 6mg/kg/Week
	Comments	GSK2402968 6mg/kg/week Vs Placebo
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.000
	Comments	No adjustment for multiplicity was made, so p-values should not be used to make conclusions with regards to statistical significance.
	Method	Mixed Effect Model for Repeated Measures
	Comments	Model included terms for treatment, visit, treatment by visit, country grouping, Baseline and Baseline by visit.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4044.99
	Confidence Interval	(2-Sided) 95%; -5232.21 to -2857.77
	Estimation Comments	[Not Specified]

11. Secondary Outcome

Title	Change From Baseline in Pulmonary Function Test Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 Second (FEV1) at Week 48
Description	The FEV1 is the volume of air forcefully exhaled in 1 second, whereas the FVC is the volume of air that can be maximally forcefully exhaled using non-invasive spirometry was conducted to determine actual and percentage values for FVC and FEV1. Baseline was defined as participants randomization assessment at Visit 3 (Day 0). Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.
Time Frame	Baseline (Day 0) and Week 48

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time point were analyzed.

Arm/Group Title		Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:		Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed		61	125
Mean (Standard Deviation); Unit of Measure: Liters
FVC at Week 48	Number Analyzed	58 participants	121 participants
		0.118 (0.1847)	0.087 (0.2337)
FEV1 at Week 48	Number Analyzed	55 participants	116 participants
		0.126 (0.2530)	0.049 (0.2997)

12. Secondary Outcome

Title	Number of Participants With Identified Mutation: DMD Exon 51 Skip (Upon Muscle Biopsies) at Week 48
Description	Biopsies were taken from their tibialis anterior muscle and few were taken from quadriceps. Total muscle ribonucleic acid (RNA) was isolated from muscle tissue sections and was analyzed by reverse transcriptase polymer chain reaction (RT-PCR). RT-PCR analysis focused on the area flanking the targeted exon 51 was performed to detect specific exon 51 skipping in muscle. Depending on the participants mutation different sets of DMD-gene specific RT and PCR primers were used. Sequence analysis was performed on isolated PCR products to confirm specific exon 51 skip band detection.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the indicated time point were analyzed.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed	59	119
Measure Type: Count of Participants; Unit of Measure: Participants
DMD Exon 51 skip, Band detected	48 81.4%	106 89.1%
DMD Exon 51 skip, No Band detected	9 15.3%	9 7.6%
DMD Exon 51 skip, No result	0 0.0%	2 1.7%
DMD Exon 51 skip, Not analyzed	2 3.4%	2 1.7%

13. Secondary Outcome

Title	Change From Baseline in Pediatric Quality of Life (PedsQL) Total Score at Week 48
Description	PedsQL version 3.0 scale is used to measure pediatric quality of life in children with neuromuscular disorders. The 25-item PedsQL encompasses 3 scales About My/My Childs Neuromuscular Disease (17 items), Communication (3 items), About Our Family Resources (5 items). A 5-point response scale is utilized (where 0=never a problem; 4=almost always a problem). It was assessed both by child and parent. PedsQL total score was calculated by reverse scoring individual items and linearly transforming the score to a 0-100 scale, where higher scores indicated better health-related quality of life. To reverse score individual items, the 0-4 scale items were transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score was then calculated as sum of items divided by number of items answered. Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48. A positive change from Baseline indicated improvement.
Time Frame	Baseline (Day 0) and Week 48

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time point were analyzed.

Arm/Group Title		Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:		Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed		61	125
Mean (Standard Deviation); Unit of Measure: Scores on a scale
Assesor child at week 48	Number Analyzed	57 participants	114 participants
		0.52 (11.313)	1.36 (11.360)
Assesor parent at week 48	Number Analyzed	58 participants	117 participants
		-0.11 (11.064)	-1.19 (11.269)

14. Secondary Outcome

Title	Change From Baseline in Pulmonary Function Test Peak Cough Flow (PCF) and Peak Flow (PF) at Week 48
Description	The PF also called peak expiratory flow rate (PEFR) is a participants maximum speed of expiration, as measured with a peak flow meter, a small, hand-held device used to monitor a participants ability to breathe out air. PCF was measured for participants wearing a nose clip and performing a maximum cough into a pocket peak flow meter. Baseline was defined as participants randomization assessment at Visit 3 (Day 0). Change from Baseline was calculated by subtracting the Baseline value from the value at Week 48.
Time Frame	Baseline (Day 0) and Week 48

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time point were analyzed.

Arm/Group Title		Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:		Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed		61	125
Mean (Standard Deviation); Unit of Measure: Liters per minute
PF at Week 48	Number Analyzed	59 participants	121 participants
		25.810 (41.5342)	11.603 (42.6964)
PCF at Week 48	Number Analyzed	59 participants	120 participants
		22.7 (42.46)	10.7 (45.04)

15. Secondary Outcome

Title	Number of Participants Who Showed Improvement on Clinician Global Impression of Improvement (CGI-I) Scale at Week 48
Description	The CGI-I is scored based on the clinician's reflection of the participant's current overall clinical condition compared to the overall clinical condition just prior to the initiation of medication use (i.e., the period prior to Randomization). The CGI-I is rated without regard to the clinician's belief that any clinical changes are or are not due to medication and without consideration of the etiology of the symptoms. The CGI-I is measured on a 7-point Likert scale (where 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse). The score ranged from 1-7, where lower score indicated more improvement and higher score indicated less improvement.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the indicated time point were analyzed.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed	57	116
Measure Type: Count of Participants; Unit of Measure: Participants
Very much improved	0 0.0%	3 2.6%
Much improved	1 1.8%	9 7.8%
Minimally improved	2 3.5%	23 19.8%
No change	27 47.4%	41 35.3%
Minimally worse	20 35.1%	30 25.9%
Much worse	6 10.5%	10 8.6%
Very much worse	1 1.8%	0 0.0%

16. Secondary Outcome

Title	Change From Baseline in Health Utilities Index (HUI) Scores at Week 48
Description	A 15-item HUI questionnaire assessed Health-related quality of life (HRQoL). Responses from 15-item HUI were used to quantify HRQoL according to 2 health status classification systems, HUI Mark 2 (HUI2) and HUI Mark 3 (HUI3). HUI2 assessed 7 HRQoL dimensions: sensation, mobility, emotion, cognition, self care, pain and fertility. HUI3 assessed 8 HRQoL dimensions: vision, hearing, speech, ambulation, dexterity, emotion, cognition and pain. Both HUI2 (range from -0.03 to 1.0) and HUI3 (range from -0.36 to 1.0) utility scores were calculated using algorithms incorporating community-derived preference weights. A utility value of 1.0 represented perfect health and a utility value of 0.0 represented death. Lowest possible HUI2 score was -0.03 and for HUI3 score was -0.36, where scores less than 0 represented health states considered worse than death. Change from Baseline was calculated by subtracting Baseline value from Week 48 value. A positive change from Baseline indicated improvement.
Time Frame	Baseline (Randomization Visit, Day 0) and Week 48

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title		Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:		Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed		61	125
Least Squares Mean (Standard Error); Unit of Measure: Scores on a scale
HUI2 at Week 48	Number Analyzed	53 participants	112 participants
		-0.052 (0.0190)	-0.023 (0.0133)
HUI3 at Week 48	Number Analyzed	56 participants	116 participants
		-0.061 (0.0266)	-0.056 (0.0188)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK2402968 6mg/kg/Week
	Comments	GSK2402968 6mg/kg/week Vs Placebo, HUI2 at Week 48
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.207
	Comments	No adjustment for multiplicity was made, so p-values should not be used to make conclusions with regards to statistical significance.
	Method	Mixed Model for Repeated Measures
	Comments	Model included terms for treatment, visit, treatment by visit, country grouping, Baseline and Baseline by visit.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.0288
	Confidence Interval	(2-Sided) 95%; -0.0161 to 0.0738
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GSK2402968 6mg/kg/Week
	Comments	GSK2402968 6mg/kg/week Vs Placebo, HUI3 at Week 48
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.880
	Comments	No adjustment for multiplicity was made, so p-values should not be used to make conclusions with regards to statistical significance.
	Method	Mixed Model for Repeated Measures
	Comments	Model included terms for treatment, visit, treatment by visit, country grouping, Baseline and Baseline by visit.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.0048
	Confidence Interval	(2-Sided) 95%; -0.0580 to 0.0676
	Estimation Comments	[Not Specified]

17. Secondary Outcome

Title	Number of Participants With Adverse Events (AE) and Severe Adverse Events (SAE)
Description	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect.
Time Frame	Up to Follow-up (Week 68)

Outcome Measure Data

Analysis Population Description

The Safety Population comprised of all participants who received at least one dose of study medication.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed	61	125
Measure Type: Count of Participants; Unit of Measure: Participants
Any AE	58 95.1%	123 98.4%
Any SAE	5 8.2%	13 10.4%

18. Secondary Outcome

Title	Number of Participants With Vital Sign Data for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) and Heart Rate (HR) of Potential Clinical Concern (PCC) at Any Visit Post-Baseline
Description	Blood pressure SBP, DBP and HR were recorded after five minutes of rest in a semi-supine position. The following changes from Baseline (Day 0) in vital signs were considered to be of potential clinical concern: DBP was defined as high (increase from Baseline >=20 and >=40 millimeters of mercury [mmHg] and low (decrease from Baseline >=20 and >=40 mmHg), SBP high (increase from Baseline >=10 and >=20 mmHg and low (decrease from Baseline >=10 and >=20 mmHg) and for HR high (increase from Baseline >=20 and >=40 beats per minute [bpm] and low (decrease from Baseline >=20 and >=40 bpm). Only those parameters for which a value of PCC was reported at any visit post-Baseline is presented.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed	61	125
Measure Type: Count of Participants; Unit of Measure: Participants
DBP, High at any visit post-Baseline	22 36.1%	52 41.6%
HR, low at any visit post-Baseline	19 31.1%	49 39.2%
HR, high at any visit post-Baseline	18 29.5%	32 25.6%
SBP, low at any visit post-Baseline	8 13.1%	7 5.6%
SBP, high at any visit post-Baseline	28 45.9%	72 57.6%

19. Secondary Outcome

Title	Number of Participants With Abnormal-clinically Significant Electrocardiogram (ECG) Findings at Any Visit Post-Baseline
Description	ECG measurements were carried out and the clinical interpretation of the ECG by the investigator was recorded as normal, abnormal but not clinically significant and abnormal clinically significant. The PCC ranges include, QT interval corrected for heart rate by Bazett's formula (QTcB) or QT interval corrected for heart rate by Fridericia's formula (QTcF) >450 milliseconds and any increase from Baseline of QTcB or QTcF. Participants were categorized as abnormal clinically significant based on the investigator's judgment and PCC ranges. Data has been presented for number of participants with abnormal clinically significant findings at any visit post-Baseline.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed	61	125
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	5 4.0%

20. Secondary Outcome

Title	Number of Participants With Hematology Parameters of PCC at Any Visit Post-Baseline
Description	Laboratory samples were collected for analysis of hematology parameters. The PCC values for hematology parameters: hematocrit was 1.02 x Upper limit of normal (ULN), for hemoglobin was 1.03 x ULN, for lymphocytes was 0.81 x lower limit of normal (LLN), for platelet count was 0.67 x LLN and 1.57 x ULN, for total neutrophils was 0.83 x LLN, and that for white blood cell count was 0.67 x LLN and value of 1.82 x ULN. Only those parameters for which a value of PCC was reported at any visit post-Baseline have been presented.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed	61	125
Measure Type: Count of Participants; Unit of Measure: Participants
Hematocrit > reference range high	12 19.7%	27 21.6%
Hemoglobin > reference range high	2 3.3%	6 4.8%
Lymphocytes < reference range low	6 9.8%	9 7.2%
Platelet count > reference range high	1 1.6%	0 0.0%
Platelet count < reference range low	0 0.0%	1 0.8%
Total neutrophils < reference range low	8 13.1%	9 7.2%
White blood cell count < reference range low	3 4.9%	4 3.2%

21. Secondary Outcome

Title	Number of Participants With Coagulation Parameters of PCC at Any Visit Post-Baseline
Description	Laboratory samples were collected for analysis of coagulation parameters. The PCC values for coagulation parameters activated partial thromboplastin time (aPTT) was 1.5 x ULN and aPTT ratio also known as international normalized ration (INR) was 1.2 x ULN. Only those parameters for which a value of PCC was reported at any visit post-Baseline is presented.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed	61	125
Measure Type: Count of Participants; Unit of Measure: Participants
aPTT > reference range high	6 9.8%	6 4.8%
INR > reference range high	11 18.0%	32 25.6%

22. Secondary Outcome

Title	Number of Participants With Clinical Chemistry Parameters of PCC at Any Visit Post-Baseline
Description	Laboratory samples were collected for analysis of chemistry parameters. The PCC values for chemistry parameters for alanine amino transferase (ALT) plus total bilirubin (TB) was >=1.5 x ULN for TB and >=2 x ULN for ALT, for albumin was 0.86 x LLN, for asparatate amino transferase (AST) was >=2 x ULN, for calcium was 0.91 x LLN and 1.06 x ULN, for glucose was 0.71 x LLN and 1.41 x ULN, for phosphorus was 0.80 x LLN and 1.14 x ULN, for sodium was 0.96 x LLN and 1.03 x ULN, for potassium was 0.86 x LLN and 1.10 x ULN and that for alkaline phosphatase was >=2x ULN. Only those parameters for which a value of PCC was reported at any visit post-Baseline is presented.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period
Overall Number of Participants Analyzed	61	125
Measure Type: Count of Participants; Unit of Measure: Participants
ALT plus TB > reference range high	0 0.0%	2 1.6%
ALT > reference range high	61 100.0%	125 100.0%
Albumin < reference range low	0 0.0%	1 0.8%
AST > reference range high	61 100.0%	125 100.0%
Calcium > reference range high	1 1.6%	3 2.4%
Calcium < reference range low	0 0.0%	3 2.4%
Glucose > reference range high	3 4.9%	5 4.0%
Glucose < reference range low	0 0.0%	2 1.6%
Phosphorus > reference range high	1 1.6%	8 6.4%
Sodium > reference range high	2 3.3%	9 7.2%
Potassium > reference range high	0 0.0%	0 0.0%
Potassium < reference range low	0 0.0%	0 0.0%
Alkaline phosphatase > reference range high	0 0.0%	0 0.0%

23. Secondary Outcome

Title	Number of Participants With Urinalysis Data Outside the Reference Range (>Reference Range High) at Any Visit Post- Baseline
Description	Urine samples were collected for analysis of abnormal urine parameters. Quantitative examination included the assessment for urine albumin excretion rate, urine alpha-1-microglobulin, urine creatinine excretion-24 hour and urine protein excretion-24 hour. Only those parameters for which a value of >reference range high was reported at any visit post-Baseline is presented.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description:		Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed		61	125
Measure Type: Count of Participants; Unit of Measure: Participants
Urine Albumin excretion rate > reference range	Number Analyzed	12 participants	93 participants
		1 8.3%	15 16.1%
Urine Protein excretion -24 hour > reference range	Number Analyzed	12 participants	96 participants
		4 33.3%	54 56.3%

24. Secondary Outcome

Title	Plasma Concentrations of GSK2402968 Following Subcutaneous Administration
Description	Blood samples for pharmacokinetic assessment were taken at Week 0 (Randomization) at 0.5, 1, 3 hours post-dose and at Week 8,12, 24, 36 and 47 at pre-dose, and between 1 and 4 hours post-dose. Data has been presented for plasma concentrations of GSK2402968 following subcutaneous administration.
Time Frame	Randomization (Week 0 at 0.5, 1 and 3 hours), Week 8 (pre-dose, 1-4 hours), Week 12 (pre-dose, 1-4 hours), Week 24 (pre-dose, 1-4 hours), Week 36 (pre-dose, 1-4 hours), Week 47 (pre-dose, 1-4 hours)

Outcome Measure Data

Analysis Population Description

The Pharmacokinetic Population comprised all participants who were randomized to the study and from whom at least one blood sample was obtained for assessment of GSK2402968 concentration. Only those participants available at the specified time points were analyzed.

Arm/Group Title		GSK2402968 6mg/kg/Week
Arm/Group Description:		Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Overall Number of Participants Analyzed		125
Median (Full Range); Unit of Measure: Nanograms per millimeter
Week 0, 0.5 hours	Number Analyzed	120 participants
		3349.595; (572.07 to 10408.94)
Week 0, 1 hour	Number Analyzed	122 participants
		4946.950; (1094.90 to 13159.51)
Week 0, 3 hour	Number Analyzed	121 participants
		5932.740; (1794.00 to 12765.26)
Week 8, Pre-dose	Number Analyzed	47 participants
		12.730; (0.00 to 4424.28)
Week 8, 1-4 hours	Number Analyzed	47 participants
		5100.220; (7.62 to 10471.64)
Week 12, Pre-dose	Number Analyzed	47 participants
		19.090; (4.60 to 50.95)
Week 12, 1-4 hours	Number Analyzed	47 participants
		5613.040; (10.89 to 10583.33)
Week 24, Pre-dose	Number Analyzed	49 participants
		40.920; (0.00 to 186.87)
Week 24, 1-4 hours	Number Analyzed	49 participants
		6141.580; (40.65 to 11902.15)
Week 36, Pre-dose	Number Analyzed	38 participants
		55.185; (22.64 to 6590.81)
Week 36, 1-4 hours	Number Analyzed	37 participants
		5755.950; (68.84 to 12967.56)
Week 47, Pre-dose	Number Analyzed	106 participants
		61.395; (3.86 to 5922.31)
Week 47, 1-4 hours	Number Analyzed	99 participants
		5266.240; (46.42 to 13841.11)

Adverse Events

Time Frame	Up to Follow-up (Week 68).
Adverse Event Reporting Description	The Safety Population was used for analysis.
Arm/Group Title	Placebo	GSK2402968 6mg/kg/Week
Arm/Group Description	Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
All-Cause Mortality
	Placebo	GSK2402968 6mg/kg/Week
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/61 (0.00%)	0/125 (0.00%)
Serious Adverse Events
	Placebo	GSK2402968 6mg/kg/Week
	Affected / at Risk (%)	Affected / at Risk (%)
Total	5/61 (8.20%)	13/125 (10.40%)
Cardiac disorders
Cardiac fibrillation † 2	0/61 (0.00%)	1/125 (0.80%)
Myocardial ischaemia † 2	0/61 (0.00%)	1/125 (0.80%)
Gastrointestinal disorders
Enteritis † 2	0/61 (0.00%)	1/125 (0.80%)
General disorders
Spinal pain † 2	0/61 (0.00%)	1/125 (0.80%)
Infections and infestations
Gastroenteritis † 2	1/61 (1.64%)	0/125 (0.00%)
Viral infection † 2	1/61 (1.64%)	0/125 (0.00%)
Injury, poisoning and procedural complications
Fall † 1	0/61 (0.00%)	1/125 (0.80%)
Femur fracture † 2	0/61 (0.00%)	2/125 (1.60%)
Head injury † 2	0/61 (0.00%)	1/125 (0.80%)
Lumbar vertebral fracture † 2	0/61 (0.00%)	1/125 (0.80%)
Patella fracture † 2	1/61 (1.64%)	0/125 (0.00%)
Toxicity to various agents † 2	1/61 (1.64%)	0/125 (0.00%)
Wound dehiscence † 2	0/61 (0.00%)	1/125 (0.80%)
Tibia fracture † 2	0/61 (0.00%)	1/125 (0.80%)
Investigations
Alanine aminotransferase increased † 2	0/61 (0.00%)	1/125 (0.80%)
International normalised ratio increased † 2	0/61 (0.00%)	1/125 (0.80%)
Metabolism and nutrition disorders
Dehydration † 2	0/61 (0.00%)	1/125 (0.80%)
Nervous system disorders
Benign intracranial hypertension † 2	0/61 (0.00%)	1/125 (0.80%)
Intercostal neuralgia † 2	1/61 (1.64%)	0/125 (0.00%)
Intracranial venous sinus thrombosis † 2	0/61 (0.00%)	1/125 (0.80%)
Renal and urinary disorders
Glomerulonephritis † 2	0/61 (0.00%)	1/125 (0.80%)
1 Term from vocabulary, MedDRA; 2 Term from vocabulary, MedDRA 16.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo	GSK2402968 6mg/kg/Week
	Affected / at Risk (%)	Affected / at Risk (%)
Total	54/61 (88.52%)	119/125 (95.20%)
Ear and labyrinth disorders
Ear pain † 1	4/61 (6.56%)	6/125 (4.80%)
Gastrointestinal disorders
Vomiting † 1	13/61 (21.31%)	28/125 (22.40%)
Diarrhoea † 1	9/61 (14.75%)	23/125 (18.40%)
Abdominal pain † 1	7/61 (11.48%)	14/125 (11.20%)
Abdominal pain upper † 1	3/61 (4.92%)	9/125 (7.20%)
General disorders
Injection site erythema † 1	4/61 (6.56%)	62/125 (49.60%)
Injection site discolouration † 1	2/61 (3.28%)	41/125 (32.80%)
Pyrexia † 1	15/61 (24.59%)	27/125 (21.60%)
Injection site pain † 1	2/61 (3.28%)	23/125 (18.40%)
Injection site reaction † 1	1/61 (1.64%)	24/125 (19.20%)
Injection site bruising † 1	6/61 (9.84%)	11/125 (8.80%)
Injection site induration † 1	0/61 (0.00%)	17/125 (13.60%)
Injection site pruritus † 1	0/61 (0.00%)	17/125 (13.60%)
Injection site haematoma † 1	2/61 (3.28%)	9/125 (7.20%)
Injection site atrophy † 1	0/61 (0.00%)	9/125 (7.20%)
Injection site urticaria † 1	0/61 (0.00%)	9/125 (7.20%)
Injection site swelling † 1	0/61 (0.00%)	8/125 (6.40%)
Infections and infestations
Nasopharyngitis † 1	25/61 (40.98%)	38/125 (30.40%)
Upper respiratory tract infection † 1	8/61 (13.11%)	15/125 (12.00%)
Gastroenteritis † 1	5/61 (8.20%)	15/125 (12.00%)
Rhinitis † 1	3/61 (4.92%)	10/125 (8.00%)
Influenza † 1	4/61 (6.56%)	7/125 (5.60%)
Ear infection † 1	5/61 (8.20%)	4/125 (3.20%)
Pharyngitis † 1	4/61 (6.56%)	5/125 (4.00%)
Bronchitis † 1	4/61 (6.56%)	4/125 (3.20%)
Injury, poisoning and procedural complications
Fall † 1	12/61 (19.67%)	26/125 (20.80%)
Contusion † 1	7/61 (11.48%)	8/125 (6.40%)
Excoriation † 1	3/61 (4.92%)	7/125 (5.60%)
Ligament sprain † 1	3/61 (4.92%)	7/125 (5.60%)
Investigations
Protein urine present † 1	4/61 (6.56%)	17/125 (13.60%)
Red blood cells urine positive † 1	4/61 (6.56%)	14/125 (11.20%)
Cystatin C increased † 1	2/61 (3.28%)	14/125 (11.20%)
Red blood cells urine † 1	4/61 (6.56%)	11/125 (8.80%)
Urine protein/creatinine ratio increased † 1	2/61 (3.28%)	11/125 (8.80%)
Blood fibrinogen decreased † 1	6/61 (9.84%)	3/125 (2.40%)
Musculoskeletal and connective tissue disorders
Pain in extremity † 1	12/61 (19.67%)	11/125 (8.80%)
Back pain † 1	5/61 (8.20%)	8/125 (6.40%)
Arthralgia † 1	1/61 (1.64%)	10/125 (8.00%)
Muscle spasms † 1	4/61 (6.56%)	5/125 (4.00%)
Nervous system disorders
Headache † 1	11/61 (18.03%)	33/125 (26.40%)
Renal and urinary disorders
Proteinuria † 1	11/61 (18.03%)	42/125 (33.60%)
Haematuria † 1	5/61 (8.20%)	21/125 (16.80%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	12/61 (19.67%)	24/125 (19.20%)
Epistaxis † 1	5/61 (8.20%)	11/125 (8.80%)
Oropharyngeal pain † 1	1/61 (1.64%)	10/125 (8.00%)
Skin and subcutaneous tissue disorders
Rash † 1	6/61 (9.84%)	3/125 (2.40%)
Erythema † 1	1/61 (1.64%)	7/125 (5.60%)
Pruritus † 1	1/61 (1.64%)	7/125 (5.60%)
1 Term from vocabulary, MedDRA 16.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: GSK Response Center
• Organization: GlaxoSmithKline
• Phone: 866-435-7343

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Goemans N, Mercuri E, Belousova E, Komaki H, Dubrovsky A, McDonald CM, Kraus JE, Lourbakos A, Lin Z, Campion G, Wang SX, Campbell C; DEMAND III study group. A randomized placebo-controlled phase 3 trial of an antisense oligonucleotide, drisapersen, in Duchenne muscular dystrophy. Neuromuscul Disord. 2018 Jan;28(1):4-15. doi: 10.1016/j.nmd.2017.10.004. Epub 2017 Dec 6.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01254019
• Other Study ID Numbers: 114044
• First Submitted: October 21, 2010
• First Posted: December 6, 2010
• Results First Submitted: September 21, 2017
• Results First Posted: January 28, 2019
• Last Update Posted: January 28, 2019