Trial Outcomes & Findings for A Clinical Study to Assess the Efficacy and Safety of GSK2402968 in Subjects With Duchenne Muscular Dystrophy (NCT NCT01254019)

Last Updated: 2019-01-28

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

186 participants

Primary outcome timeframe

Baseline (Day 0) and Week 48

Results posted on

2019-01-28

Participant Flow

This study was conducted across 44 centers in 19 countries from 02 December 2010 to 28 June 2013.

A total of 186 participants were randomized which included males with a maximum age of 16 years, no adults were included in this study.

Participant milestones

Participant milestones
Measure	Placebo Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week 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.
Overall Study STARTED	61	125
Overall Study COMPLETED	60	121
Overall Study NOT COMPLETED	1	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week 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.
Overall Study Adverse Event	0	2
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	0	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=61 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=125 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.	Total n=186 Participants Total of all reporting groups
Age, Continuous	8.0 Years STANDARD_DEVIATION 2.37 • n=5 Participants	8.3 Years STANDARD_DEVIATION 2.43 • n=7 Participants	8.2 Years STANDARD_DEVIATION 2.41 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	61 Participants n=5 Participants	125 Participants n=7 Participants	186 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	5 Participants n=5 Participants	9 Participants n=7 Participants	14 Participants n=5 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	46 Participants n=5 Participants	95 Participants n=7 Participants	141 Participants n=5 Participants
Race/Ethnicity, Customized White - Mixed Race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Mixed Race	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 0) and Week 48

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=117 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Change From Baseline in Muscle Function Using the 6 Minute Walking Distance (6MWD) Test Assessed at Week 48	-52.65 Meters Standard Error 10.423	-42.32 Meters Standard Error 7.378

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 48

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=117 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Change From Baseline in the Linearized North Star Ambulatory Assessment (NSAA) Total Score at Week 48	-6.7 Scores on a scale Standard Error 1.43	-7.2 Scores on a scale Standard Error 1.01

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 48

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=55 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=111 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Change From Baseline in the 4 Stair Climb (Ascent) Velocity at Week 48	-0.12 Stairs per second Standard Error 0.049	-0.14 Stairs per second Standard Error 0.035

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 48

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=117 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Change From Baseline in the 10-meter Walk/Run Velocity at Week 48	-0.20 Meters per second Standard Error 0.050	-0.21 Meters per second Standard Error 0.035

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 48

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=44 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=91 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Change From Baseline in the Timed Function Test Rise From Floor at Week 48	7.48 Seconds Standard Error 2.080	6.36 Seconds Standard Error 1.463

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 48

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=55 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=109 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Change From Baseline in the 4 Stair Climb (Descent) Velocity at Week 48	-0.15 Stairs per second Standard Error 0.052	-0.11 Stairs per second Standard Error 0.037

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 48

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=58 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=118 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Change From Baseline in Muscle Strength (Total Score) at Week 48	-1.21 Pounds Standard Error 2.729	-2.18 Pounds Standard Error 1.926

SECONDARY outcome

Timeframe: Week 48

Population: ITT Population.

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.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=125 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Kaplan-Meier Estimates for Time to Loss of Ambulation	NA Days Median, upper limit and lower limit was not reached due to insufficient number of participants with events.	NA Days Interval 390.0 to Median and upper limit was not reached due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: Week 48

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=53 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=103 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Number of Participants Who Experienced Accidental Falls During 6MWD Assessments at Week 48 Number of falls=0	48 Participants	102 Participants
Number of Participants Who Experienced Accidental Falls During 6MWD Assessments at Week 48 Number of falls=1	5 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 48

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=118 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Change From Baseline in Creatine Kinase Serum Concentrations at Week 48	-1228.5 International units per liter Standard Error 500.59	-5273.5 International units per liter Standard Error 359.05

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 48

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=125 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Change From Baseline in Pulmonary Function Test Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 Second (FEV1) at Week 48 FVC at Week 48	0.118 Liters Standard Deviation 0.1847	0.087 Liters Standard Deviation 0.2337
Change From Baseline in Pulmonary Function Test Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 Second (FEV1) at Week 48 FEV1 at Week 48	0.126 Liters Standard Deviation 0.2530	0.049 Liters Standard Deviation 0.2997

SECONDARY outcome

Timeframe: Week 48

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=59 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=119 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Number of Participants With Identified Mutation: DMD Exon 51 Skip (Upon Muscle Biopsies) at Week 48 DMD Exon 51 skip, Band detected	48 Participants	106 Participants
Number of Participants With Identified Mutation: DMD Exon 51 Skip (Upon Muscle Biopsies) at Week 48 DMD Exon 51 skip, No Band detected	9 Participants	9 Participants
Number of Participants With Identified Mutation: DMD Exon 51 Skip (Upon Muscle Biopsies) at Week 48 DMD Exon 51 skip, No result	0 Participants	2 Participants
Number of Participants With Identified Mutation: DMD Exon 51 Skip (Upon Muscle Biopsies) at Week 48 DMD Exon 51 skip, Not analyzed	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 48

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=125 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Change From Baseline in Pediatric Quality of Life (PedsQL) Total Score at Week 48 Assesor child at week 48	0.52 Scores on a scale Standard Deviation 11.313	1.36 Scores on a scale Standard Deviation 11.360
Change From Baseline in Pediatric Quality of Life (PedsQL) Total Score at Week 48 Assesor parent at week 48	-0.11 Scores on a scale Standard Deviation 11.064	-1.19 Scores on a scale Standard Deviation 11.269

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 48

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=125 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Change From Baseline in Pulmonary Function Test Peak Cough Flow (PCF) and Peak Flow (PF) at Week 48 PF at Week 48	25.810 Liters per minute Standard Deviation 41.5342	11.603 Liters per minute Standard Deviation 42.6964
Change From Baseline in Pulmonary Function Test Peak Cough Flow (PCF) and Peak Flow (PF) at Week 48 PCF at Week 48	22.7 Liters per minute Standard Deviation 42.46	10.7 Liters per minute Standard Deviation 45.04

SECONDARY outcome

Timeframe: Week 48

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=57 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=116 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Number of Participants Who Showed Improvement on Clinician Global Impression of Improvement (CGI-I) Scale at Week 48 Much worse	6 Participants	10 Participants
Number of Participants Who Showed Improvement on Clinician Global Impression of Improvement (CGI-I) Scale at Week 48 Very much improved	0 Participants	3 Participants
Number of Participants Who Showed Improvement on Clinician Global Impression of Improvement (CGI-I) Scale at Week 48 Much improved	1 Participants	9 Participants
Number of Participants Who Showed Improvement on Clinician Global Impression of Improvement (CGI-I) Scale at Week 48 Minimally improved	2 Participants	23 Participants
Number of Participants Who Showed Improvement on Clinician Global Impression of Improvement (CGI-I) Scale at Week 48 No change	27 Participants	41 Participants
Number of Participants Who Showed Improvement on Clinician Global Impression of Improvement (CGI-I) Scale at Week 48 Minimally worse	20 Participants	30 Participants
Number of Participants Who Showed Improvement on Clinician Global Impression of Improvement (CGI-I) Scale at Week 48 Very much worse	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Randomization Visit, Day 0) and Week 48

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=125 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Change From Baseline in Health Utilities Index (HUI) Scores at Week 48 HUI2 at Week 48	-0.052 Scores on a scale Standard Error 0.0190	-0.023 Scores on a scale Standard Error 0.0133
Change From Baseline in Health Utilities Index (HUI) Scores at Week 48 HUI3 at Week 48	-0.061 Scores on a scale Standard Error 0.0266	-0.056 Scores on a scale Standard Error 0.0188

SECONDARY outcome

Timeframe: Up to Follow-up (Week 68)

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=125 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Number of Participants With Adverse Events (AE) and Severe Adverse Events (SAE) Any AE	58 Participants	123 Participants
Number of Participants With Adverse Events (AE) and Severe Adverse Events (SAE) Any SAE	5 Participants	13 Participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: Safety Population.

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.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=125 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
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 DBP, High at any visit post-Baseline	22 Participants	52 Participants
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 HR, low at any visit post-Baseline	19 Participants	49 Participants
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 HR, high at any visit post-Baseline	18 Participants	32 Participants
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 SBP, low at any visit post-Baseline	8 Participants	7 Participants
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 SBP, high at any visit post-Baseline	28 Participants	72 Participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: Safety Population.

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.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=125 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Number of Participants With Abnormal-clinically Significant Electrocardiogram (ECG) Findings at Any Visit Post-Baseline	0 Participants	5 Participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: Safety Population.

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.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=125 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Number of Participants With Hematology Parameters of PCC at Any Visit Post-Baseline Hematocrit > reference range high	12 Participants	27 Participants
Number of Participants With Hematology Parameters of PCC at Any Visit Post-Baseline Hemoglobin > reference range high	2 Participants	6 Participants
Number of Participants With Hematology Parameters of PCC at Any Visit Post-Baseline Lymphocytes < reference range low	6 Participants	9 Participants
Number of Participants With Hematology Parameters of PCC at Any Visit Post-Baseline Platelet count > reference range high	1 Participants	0 Participants
Number of Participants With Hematology Parameters of PCC at Any Visit Post-Baseline Platelet count < reference range low	0 Participants	1 Participants
Number of Participants With Hematology Parameters of PCC at Any Visit Post-Baseline Total neutrophils < reference range low	8 Participants	9 Participants
Number of Participants With Hematology Parameters of PCC at Any Visit Post-Baseline White blood cell count < reference range low	3 Participants	4 Participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: Safety Population.

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.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=125 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Number of Participants With Coagulation Parameters of PCC at Any Visit Post-Baseline aPTT > reference range high	6 Participants	6 Participants
Number of Participants With Coagulation Parameters of PCC at Any Visit Post-Baseline INR > reference range high	11 Participants	32 Participants

SECONDARY outcome

Timeframe: Up to Week 48

Population: Safety Population.

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.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=125 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Number of Participants With Clinical Chemistry Parameters of PCC at Any Visit Post-Baseline ALT plus TB > reference range high	0 Participants	2 Participants
Number of Participants With Clinical Chemistry Parameters of PCC at Any Visit Post-Baseline ALT > reference range high	61 Participants	125 Participants
Number of Participants With Clinical Chemistry Parameters of PCC at Any Visit Post-Baseline Albumin < reference range low	0 Participants	1 Participants
Number of Participants With Clinical Chemistry Parameters of PCC at Any Visit Post-Baseline AST > reference range high	61 Participants	125 Participants
Number of Participants With Clinical Chemistry Parameters of PCC at Any Visit Post-Baseline Calcium > reference range high	1 Participants	3 Participants
Number of Participants With Clinical Chemistry Parameters of PCC at Any Visit Post-Baseline Calcium < reference range low	0 Participants	3 Participants
Number of Participants With Clinical Chemistry Parameters of PCC at Any Visit Post-Baseline Glucose > reference range high	3 Participants	5 Participants
Number of Participants With Clinical Chemistry Parameters of PCC at Any Visit Post-Baseline Glucose < reference range low	0 Participants	2 Participants
Number of Participants With Clinical Chemistry Parameters of PCC at Any Visit Post-Baseline Phosphorus > reference range high	1 Participants	8 Participants
Number of Participants With Clinical Chemistry Parameters of PCC at Any Visit Post-Baseline Sodium > reference range high	2 Participants	9 Participants
Number of Participants With Clinical Chemistry Parameters of PCC at Any Visit Post-Baseline Potassium > reference range high	0 Participants	0 Participants
Number of Participants With Clinical Chemistry Parameters of PCC at Any Visit Post-Baseline Potassium < reference range low	0 Participants	0 Participants
Number of Participants With Clinical Chemistry Parameters of PCC at Any Visit Post-Baseline Alkaline phosphatase > reference range high	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 48

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

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.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=125 Participants Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Number of Participants With Urinalysis Data Outside the Reference Range (>Reference Range High) at Any Visit Post- Baseline Urine Albumin excretion rate > reference range	1 Participants	15 Participants
Number of Participants With Urinalysis Data Outside the Reference Range (>Reference Range High) at Any Visit Post- Baseline Urine Protein excretion -24 hour > reference range	4 Participants	54 Participants

SECONDARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=125 Participants Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Plasma Concentrations of GSK2402968 Following Subcutaneous Administration Week 47, Pre-dose	61.395 Nanograms per millimeter Interval 3.86 to 5922.31	—
Plasma Concentrations of GSK2402968 Following Subcutaneous Administration Week 0, 0.5 hours	3349.595 Nanograms per millimeter Interval 572.07 to 10408.94	—
Plasma Concentrations of GSK2402968 Following Subcutaneous Administration Week 0, 1 hour	4946.950 Nanograms per millimeter Interval 1094.9 to 13159.51	—
Plasma Concentrations of GSK2402968 Following Subcutaneous Administration Week 0, 3 hour	5932.740 Nanograms per millimeter Interval 1794.0 to 12765.26	—
Plasma Concentrations of GSK2402968 Following Subcutaneous Administration Week 8, Pre-dose	12.730 Nanograms per millimeter Interval 0.0 to 4424.28	—
Plasma Concentrations of GSK2402968 Following Subcutaneous Administration Week 8, 1-4 hours	5100.220 Nanograms per millimeter Interval 7.62 to 10471.64	—
Plasma Concentrations of GSK2402968 Following Subcutaneous Administration Week 12, Pre-dose	19.090 Nanograms per millimeter Interval 4.6 to 50.95	—
Plasma Concentrations of GSK2402968 Following Subcutaneous Administration Week 12, 1-4 hours	5613.040 Nanograms per millimeter Interval 10.89 to 10583.33	—
Plasma Concentrations of GSK2402968 Following Subcutaneous Administration Week 24, Pre-dose	40.920 Nanograms per millimeter Interval 0.0 to 186.87	—
Plasma Concentrations of GSK2402968 Following Subcutaneous Administration Week 24, 1-4 hours	6141.580 Nanograms per millimeter Interval 40.65 to 11902.15	—
Plasma Concentrations of GSK2402968 Following Subcutaneous Administration Week 36, Pre-dose	55.185 Nanograms per millimeter Interval 22.64 to 6590.81	—
Plasma Concentrations of GSK2402968 Following Subcutaneous Administration Week 36, 1-4 hours	5755.950 Nanograms per millimeter Interval 68.84 to 12967.56	—
Plasma Concentrations of GSK2402968 Following Subcutaneous Administration Week 47, 1-4 hours	5266.240 Nanograms per millimeter Interval 46.42 to 13841.11	—

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 54 other events

Deaths: 0 deaths

GSK2402968 6mg/kg/Week

Serious events: 13 serious events

Other events: 119 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=61 participants at risk Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=125 participants at risk Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
Injury, poisoning and procedural complications Fall	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.80% 1/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	1.6% 2/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Injury, poisoning and procedural complications Head injury	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.80% 1/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.80% 1/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Injury, poisoning and procedural complications Patella fracture	1.6% 1/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.00% 0/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Injury, poisoning and procedural complications Toxicity to various agents	1.6% 1/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.00% 0/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.80% 1/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Nervous system disorders Benign intracranial hypertension	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.80% 1/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Nervous system disorders Intercostal neuralgia	1.6% 1/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.00% 0/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Nervous system disorders Intracranial venous sinus thrombosis	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.80% 1/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Cardiac disorders Cardiac fibrillation	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.80% 1/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Cardiac disorders Myocardial ischaemia	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.80% 1/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Infections and infestations Gastroenteritis	1.6% 1/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.00% 0/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Infections and infestations Viral infection	1.6% 1/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.00% 0/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Gastrointestinal disorders Enteritis	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.80% 1/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
General disorders Spinal pain	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.80% 1/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Investigations Alanine aminotransferase increased	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.80% 1/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Investigations International normalised ratio increased	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.80% 1/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Metabolism and nutrition disorders Dehydration	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.80% 1/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Renal and urinary disorders Glomerulonephritis	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.80% 1/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	0.80% 1/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.

Measure	Placebo n=61 participants at risk Participants received single dose of matching placebo sterile solution for subcutaneous injection preferably in the morning over the 48 week treatment period.	GSK2402968 6mg/kg/Week n=125 participants at risk Participants received single dose of GSK2402968 6 mg/kg/week subcutaneous injection preferably in the morning over the 48 week treatment period.
General disorders Injection site erythema	6.6% 4/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	49.6% 62/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
General disorders Injection site discolouration	3.3% 2/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	32.8% 41/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
General disorders Pyrexia	24.6% 15/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	21.6% 27/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
General disorders Injection site pain	3.3% 2/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	18.4% 23/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
General disorders Injection site reaction	1.6% 1/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	19.2% 24/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
General disorders Injection site bruising	9.8% 6/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	8.8% 11/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
General disorders Injection site induration	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	13.6% 17/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
General disorders Injection site pruritus	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	13.6% 17/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
General disorders Injection site haematoma	3.3% 2/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	7.2% 9/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
General disorders Injection site atrophy	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	7.2% 9/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
General disorders Injection site urticaria	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	7.2% 9/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
General disorders Injection site swelling	0.00% 0/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	6.4% 8/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Infections and infestations Nasopharyngitis	41.0% 25/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	30.4% 38/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Infections and infestations Upper respiratory tract infection	13.1% 8/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	12.0% 15/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Infections and infestations Gastroenteritis	8.2% 5/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	12.0% 15/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Infections and infestations Rhinitis	4.9% 3/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	8.0% 10/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Infections and infestations Influenza	6.6% 4/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	5.6% 7/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Infections and infestations Ear infection	8.2% 5/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	3.2% 4/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Infections and infestations Pharyngitis	6.6% 4/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	4.0% 5/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Infections and infestations Bronchitis	6.6% 4/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	3.2% 4/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Gastrointestinal disorders Vomiting	21.3% 13/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	22.4% 28/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Gastrointestinal disorders Diarrhoea	14.8% 9/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	18.4% 23/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Gastrointestinal disorders Abdominal pain	11.5% 7/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	11.2% 14/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Gastrointestinal disorders Abdominal pain upper	4.9% 3/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	7.2% 9/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Renal and urinary disorders Proteinuria	18.0% 11/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	33.6% 42/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Renal and urinary disorders Haematuria	8.2% 5/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	16.8% 21/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Injury, poisoning and procedural complications Fall	19.7% 12/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	20.8% 26/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Injury, poisoning and procedural complications Contusion	11.5% 7/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	6.4% 8/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Injury, poisoning and procedural complications Excoriation	4.9% 3/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	5.6% 7/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Injury, poisoning and procedural complications Ligament sprain	4.9% 3/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	5.6% 7/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Investigations Protein urine present	6.6% 4/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	13.6% 17/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Investigations Red blood cells urine positive	6.6% 4/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	11.2% 14/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Investigations Cystatin C increased	3.3% 2/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	11.2% 14/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Investigations Red blood cells urine	6.6% 4/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	8.8% 11/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Investigations Urine protein/creatinine ratio increased	3.3% 2/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	8.8% 11/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Investigations Blood fibrinogen decreased	9.8% 6/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	2.4% 3/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Respiratory, thoracic and mediastinal disorders Cough	19.7% 12/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	19.2% 24/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Respiratory, thoracic and mediastinal disorders Epistaxis	8.2% 5/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	8.8% 11/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.6% 1/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	8.0% 10/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Nervous system disorders Headache	18.0% 11/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	26.4% 33/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Musculoskeletal and connective tissue disorders Pain in extremity	19.7% 12/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	8.8% 11/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Musculoskeletal and connective tissue disorders Back pain	8.2% 5/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	6.4% 8/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Musculoskeletal and connective tissue disorders Arthralgia	1.6% 1/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	8.0% 10/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Musculoskeletal and connective tissue disorders Muscle spasms	6.6% 4/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	4.0% 5/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Skin and subcutaneous tissue disorders Rash	9.8% 6/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	2.4% 3/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Skin and subcutaneous tissue disorders Erythema	1.6% 1/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	5.6% 7/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Skin and subcutaneous tissue disorders Pruritus	1.6% 1/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	5.6% 7/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.
Ear and labyrinth disorders Ear pain	6.6% 4/61 • Up to Follow-up (Week 68). The Safety Population was used for analysis.	4.8% 6/125 • Up to Follow-up (Week 68). The Safety Population was used for analysis.