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    Clinical Trial Results:
    A Randomized, Double Blind, Placebo-Controlled, Study to Assess the Efficacy, Safety, and Tolerability of RO7239361 in Ambulatory Boys with Duchenne Muscular Dystrophy

    Summary
    EudraCT number
    		 2016-001654-18
    Trial protocol
    		 SE   DE   BE   GB   ES   NL   FR   IT  
    Global end of trial date
    28 Apr 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Nov 2020
    First version publication date
    07 Nov 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    WN40227
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03039686
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001793-PIP01-15
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    28 Apr 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Apr 2020
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to compare the efficacy of RO7239361 to placebo in ambulatory boys with Duchenne muscular dystrophy (DMD). In addition, the safety and tolerability of RO7239361 were assessed.
    Protection of trial subjects
    All study subjects and parents, guardians, or legally acceptable representatives were required to read and sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Jul 2017
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 6 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 6
    Country: Number of subjects enrolled
    Australia: 18
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Canada: 9
    Country: Number of subjects enrolled
    Germany: 5
    Country: Number of subjects enrolled
    Spain: 13
    Country: Number of subjects enrolled
    France: 13
    Country: Number of subjects enrolled
    United Kingdom: 5
    Country: Number of subjects enrolled
    Italy: 12
    Country: Number of subjects enrolled
    Japan: 17
    Country: Number of subjects enrolled
    Netherlands: 5
    Country: Number of subjects enrolled
    Sweden: 3
    Country: Number of subjects enrolled
    United States: 58
    Worldwide total number of subjects
    166
    EEA total number of subjects
    58
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    166
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Subjects were recruited at sites in 13 countries.

    Pre-assignment
    Screening details
    		 Ambulatory boys, 6 to 11 years of age, with Duchenne Muscular Dystrophy (DMD) were randomized (1:1:1) to receive either low or high dose of RO7239361 or placebo.

    Period 1
    Period 1 title
    Double-blind Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind period.

    Arm title
    		 RO7239361 Low Dose
    Arm description
    		 Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
    Arm type
    		 Experimental

    Investigational medicinal product name
    RO7239361
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received low dose RO7239361 SC on specified days of the 48-week DB period.

    Arm title
    		 RO7239361 High Dose
    Arm description
    		 Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
    Arm type
    		 Experimental

    Investigational medicinal product name
    RO7239361
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received high dose RO7239361 SC on specified days of the 48-week DB period.

    Number of subjects in period 1
    		Placebo RO7239361 Low Dose RO7239361 High Dose
    Started
    56
    55
    55
    Completed
    29
    26
    32
    Not completed
    27
    29
    23
         Adverse event, serious fatal
    -
    -
    1
         Consent withdrawn by subject
    2
    2
    1
         Subject Request to Discontinue Study Treatment
    1
    2
    -
         Administrative Reason by Sponsor
    24
    25
    21
    Period 2
    Period 2 title
    Open Label Period
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 RO7239361 Low Dose
    Arm description
    		 Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label (OL) period followed by 24 weeks of follow-up.
    Arm type
    		 Experimental

    Investigational medicinal product name
    RO7239361
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received low dose RO7239361 SC on specified days for up to 192 weeks during the open-label period.

    Arm title
    		 RO7239361 High Dose
    Arm description
    		 Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label (OL) period followed by 24 weeks of follow-up.
    Arm type
    		 Experimental

    Investigational medicinal product name
    RO7239361
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received high dose RO7239361 SC on specified days for up to 192 weeks during the open-label period.

    Number of subjects in period 2 [1]
    		RO7239361 Low Dose RO7239361 High Dose
    Started
    38
    42
    Completed
    0
    0
    Not completed
    38
    42
         Consent withdrawn by subject
    3
    1
         Subject Request to Discontinue Study Treatment
    1
    -
         Administrative Reason by Sponsor
    34
    41
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Subjects from the placebo arm in the double-blind period entered the RO7239361 Low Dose and High Dose arms in the open label period as indicated.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.

    Reporting group title
    RO7239361 Low Dose
    Reporting group description
    		 Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.

    Reporting group title
    RO7239361 High Dose
    Reporting group description
    		 Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.

    Reporting group values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose Total
    Number of subjects
    		 56 55 55 166
    Age Categorical
    Units: participants
        Children (2-11 years)
    		 56 55 55 166
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 8.4 ± 1.7 8.5 ± 1.8 8.4 ± 1.5 -
    Sex: Female, Male
    Units: participants
        Female
    		 0 0 0 0
        Male
    		 56 55 55 166

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period. Following the DB period participants received low dose or high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.

    Reporting group title
    RO7239361 Low Dose
    Reporting group description
    		 Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.

    Reporting group title
    RO7239361 High Dose
    Reporting group description
    		 Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.
    Reporting group title
    RO7239361 Low Dose
    Reporting group description
    		 Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label (OL) period followed by 24 weeks of follow-up.

    Reporting group title
    RO7239361 High Dose
    Reporting group description
    		 Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label (OL) period followed by 24 weeks of follow-up.

    Subject analysis set title
    RO7239361 Low Dose Whole Study
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received low dose SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.

    Subject analysis set title
    RO7239361 High Dose Whole Study
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants received high dose SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.

    Primary: Baseline for the North Star Ambulatory Assessment (NSAA) Total Score

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    End point title
    		 Baseline for the North Star Ambulatory Assessment (NSAA) Total Score [1]
    End point description
    The NSAA is a functional scale specifically designed for ambulant boys with Duchenne muscular dystrophy (DMD) that can provide information about motor function. The NSAA is a 17-item test of standing, ability to transition from lying to sitting, sitting to standing, and other mobility assessments. Each of the 17 items is evaluated on an ordinal scale of 0-2: 0 = unable to achieve independently, 1 = modified method but achieves goal independent of physical assistance from another, or 2 = normal with no obvious modification of activity. Total score range is 0 to 34. Higher scores reflect better performance. Intent-to-Treat (ITT) population included all enrolled participants who received a randomization treatment assignment.
    End point type
    Primary
    End point timeframe
    Baseline
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was performed for the baseline NSAA total score.
    End point values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose
    Number of subjects analysed
    56
    55
    55
    Units: score on a scale
        arithmetic mean (standard deviation)
    23.1 ± 6.4
    24.5 ± 5.5
    22.7 ± 6.7
    No statistical analyses for this end point

    Primary: Change from Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 48

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    End point title
    		 Change from Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 48
    End point description
    The NSAA is a functional scale specifically designed for ambulant boys with Duchenne muscular dystrophy (DMD) that can provide information about motor function. The NSAA is a 17-item test of standing, ability to transition from lying to sitting, sitting to standing, and other mobility assessments. Each of the 17 items is evaluated on an ordinal scale of 0-2: 0 = unable to achieve independently, 1 = modified method but achieves goal independent of physical assistance from another, or 2 = normal with no obvious modification of activity. Total score range is 0 to 34. Higher scores reflect better performance. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). ITT population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=30, Low Dose n=29, High Dose n=33.
    End point type
    Primary
    End point timeframe
    Baseline, Week 48
    End point values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose
    Number of subjects analysed
    56
    55
    55
    Units: score on a scale
        least squares mean (standard error)
    -2.99 ± 0.65
    -3.44 ± 0.67
    -2.41 ± 0.64
    Statistical analysis title
    		 RO7239361 Low Dose versus Placebo
    Statistical analysis description
    Based on the MMRM using an unstructured covariance matrix -change = Baseline + Age Interactive response system (IXRS) Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.
    Comparison groups
    Placebo v RO7239361 Low Dose
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.17
         upper limit
    		 1.27
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.87
    Statistical analysis title
    		 RO7239361 High Dose versus Placebo
    Statistical analysis description
    Based on the MMRM using an unstructured covariance matrix -change = Baseline + Age Interactive response system (IXRS) Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.
    Comparison groups
    Placebo v RO7239361 High Dose
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.1
         upper limit
    		 2.26
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.85

    Secondary: Baseline Time for 4 Stair Climb

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    End point title
    		 Baseline Time for 4 Stair Climb
    End point description
    The time to complete the 4 stair climb was measured at baseline. ITT population included all enrolled participants who received a randomization treatment assignment.
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose
    Number of subjects analysed
    56
    55
    55
    Units: seconds (secs)
        arithmetic mean (standard deviation)
    3.81 ± 1.55
    3.85 ± 1.61
    3.92 ± 1.91
    No statistical analyses for this end point

    Secondary: Change from Baseline at Week 48 in the 4 Stair Climb Velocity (4SCV)

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    End point title
    		 Change from Baseline at Week 48 in the 4 Stair Climb Velocity (4SCV)
    End point description
    4SCV was calculated as the ratio of the number of stairs climbed (4) divided by the number of seconds taken to complete the 4-stair climb. The results were converted into velocity (distance/time). A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). ITT population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=30, Low Dose n=29, High Dose n=33.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 48
    End point values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose
    Number of subjects analysed
    56
    55
    55
    Units: stairs/sec
        least squares mean (standard error)
    -0.15 ± 0.07
    -0.15 ± 0.07
    -0.07 ± 0.07
    Statistical analysis title
    		 RO7239361 Low Dose versus Placebo
    Statistical analysis description
    Based on the MMRM using an unstructured covariance matrix -change = Baseline + Age Interactive response system (IXRS) Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.
    Comparison groups
    Placebo v RO7239361 Low Dose
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.21
         upper limit
    		 0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1
    Statistical analysis title
    		 RO7239361 High Dose versus Placebo
    Statistical analysis description
    Based on the MMRM using an unstructured covariance matrix -change = Baseline + Age Interactive response system (IXRS) Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.
    Comparison groups
    Placebo v RO7239361 High Dose
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.12
         upper limit
    		 0.27
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1

    Secondary: Baseline for the Time to Stand from Supine

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    End point title
    		 Baseline for the Time to Stand from Supine
    End point description
    The time required for a participant to stand from supine position. A longer time reflects a worse outcome. ITT population included all enrolled participants who received a randomization treatment assignment.
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose
    Number of subjects analysed
    56
    55
    55
    Units: secs
        arithmetic mean (standard deviation)
    6.28 ± 4.75
    6.15 ± 4.07
    7.24 ± 9.22
    No statistical analyses for this end point

    Secondary: Change from Baseline at Week 48 in Stand from Supine Velocity

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    End point title
    		 Change from Baseline at Week 48 in Stand from Supine Velocity
    End point description
    The time required for a participant to stand from supine position. A lower velocity reflects a worse outcome. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). ITT population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=28, Low Dose n=28, High Dose n=32.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 48
    End point values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose
    Number of subjects analysed
    56
    55
    55
    Units: 1/sec
        least squares mean (standard error)
    -0.05 ± 0.01
    -0.02 ± 0.01
    -0.02 ± 0.01
    Statistical analysis title
    		 RO7239361 Low Dose versus Placebo
    Statistical analysis description
    Based on the MMRM using an unstructured covariance matrix -change = Baseline + Age Interactive response system (IXRS) Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.
    Comparison groups
    Placebo v RO7239361 Low Dose
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0.06
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.02
    Statistical analysis title
    		 RO7239361 High Dose versus Placebo
    Statistical analysis description
    Based on the MMRM using an unstructured covariance matrix -change = Baseline + Age Interactive response system (IXRS) Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.
    Comparison groups
    Placebo v RO7239361 High Dose
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 0.06
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.02

    Secondary: Baseline for 10 Meter Walk/Run

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    End point title
    		 Baseline for 10 Meter Walk/Run
    End point description
    The time required for a participant to run or walk a distance of 10 meters as quickly as possible. A longer time reflects a worse outcome. ITT population included all enrolled participants who received a randomization treatment assignment.
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose
    Number of subjects analysed
    56
    55
    55
    Units: secs
        arithmetic mean (standard deviation)
    5.38 ± 1.48
    5.51 ± 1.68
    5.68 ± 2.30
    No statistical analyses for this end point

    Secondary: Change from Baseline at Week 48 in 10 M Walk/Run Velocity

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    End point title
    		 Change from Baseline at Week 48 in 10 M Walk/Run Velocity
    End point description
    The time required for a participant to run or walk a distance of 10 meters as quickly as possible calculated as velocity (distance/time). A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). ITT population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=30, Low Dose n=29, High Dose n=31.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 48
    End point values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose
    Number of subjects analysed
    56
    55
    55
    Units: m/sec
        least squares mean (standard error)
    -0.23 ± 0.06
    -0.14 ± 0.07
    -0.23 ± 0.06
    Statistical analysis title
    		 RO7239361 Low Dose versus Placebo
    Statistical analysis description
    Based on the MMRM using an unstructured covariance matrix -change = Baseline + Age Interactive response system (IXRS) Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.
    Comparison groups
    Placebo v RO7239361 Low Dose
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.08
         upper limit
    		 0.27
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09
    Statistical analysis title
    		 RO7239361 High Dose versus Placebo
    Statistical analysis description
    Based on the MMRM using an unstructured covariance matrix -change = Baseline + Age Interactive response system (IXRS) Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.
    Comparison groups
    Placebo v RO7239361 High Dose
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.17
         upper limit
    		 0.18
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.09

    Secondary: Baseline for the Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale

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    End point title
    		 Baseline for the Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale
    End point description
    The PODCI is designed to be completed by the parent/guardian of a child who has knowledge of the child's conditions. The Transfer and Basic Mobility scale is one of the subscales of the PODCI. The results are standardized into a scale of 0-100 with a higher score reflecting better performance. ITT population included all enrolled participants who received a randomization treatment assignment.
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose
    Number of subjects analysed
    56
    55
    55
    Units: score on a scale
        arithmetic mean (standard deviation)
    85.59 ± 10.21
    86.54 ± 9.52
    84.47 ± 14.76
    No statistical analyses for this end point

    Secondary: Change from Baseline at Week 48 in Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale

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    End point title
    		 Change from Baseline at Week 48 in Pediatric Outcome Data Collection Instrument (PODCI) Transfer and Basic Mobility Subscale
    End point description
    The PODCI is designed to be completed by the parent/guardian of a child who has knowledge of the child's conditions. The Transfer and Basic Mobility scale is one of the subscales of the PODCI. The results are standardized into a scale of 0-100 with a higher score reflecting better performance. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). ITT population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=31, Low Dose n=29, High Dose n=34.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 48
    End point values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose
    Number of subjects analysed
    56
    55
    55
    Units: score on a scale
        least squares mean (standard error)
    -5.47 ± 1.79
    -7.47 ± 1.83
    -4.51 ± 1.77
    Statistical analysis title
    		 RO7239361 Low Dose versus Placebo
    Statistical analysis description
    Based on the MMRM using an unstructured covariance matrix -change = Baseline + Age Interactive response system (IXRS) Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.
    Comparison groups
    Placebo v RO7239361 Low Dose
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.76
         upper limit
    		 2.77
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.41
    Statistical analysis title
    		 RO7239361 High Dose versus Placebo
    Statistical analysis description
    Based on the MMRM using an unstructured covariance matrix -change = Baseline + Age Interactive response system (IXRS) Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.
    Comparison groups
    Placebo v RO7239361 High Dose
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.71
         upper limit
    		 5.63
    Variability estimate
    Standard error of the mean
    Dispersion value
    2.36

    Secondary: Change from Baseline at Week 48 in Proximal Lower Extremity Flexor Strength

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    End point title
    		 Change from Baseline at Week 48 in Proximal Lower Extremity Flexor Strength
    End point description
    Proximal lower extremity flexor (knee extension and knee flexion) strength was measured using manual myometry. A higher score reflects a better outcome. A positive change from baseline indicates an improvement. ITT population included all enrolled participants who received a randomization treatment assignment. Number analyzed is the number of participants with data available for analyses at the given timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 48
    End point values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose
    Number of subjects analysed
    56
    55
    55
    Units: kilogram (kg)
    arithmetic mean (standard deviation)
        Baseline: Knee Extenders (n=56, 55, 54)
    5.58 ± 2.87
    6.25 ± 3.63
    5.76 ± 3.53
        Change at Week 48: Knee Extenders (n=30, 28, 33)
    -1.19 ± 2.13
    -0.47 ± 2.43
    -0.88 ± 2.97
        Baseline: Knee Flexors (n=56, 55, 54)
    5.04 ± 2.58
    5.70 ± 3.08
    5.04 ± 2.72
        Change at Week 48: Knee Flexors (n=30, 28, 33)
    0.15 ± 2.24
    0.08 ± 2.53
    -0.13 ± 2.29
    No statistical analyses for this end point

    Secondary: Baseline for the 6 Minute Walk Distance (6MWD)

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    End point title
    		 Baseline for the 6 Minute Walk Distance (6MWD)
    End point description
    The 6MWD measured the distance a participant was able to traverse while walking for 6 minutes. A longer distance reflects a better outcome. ITT population included all enrolled participants who received a randomization treatment assignment.
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose
    Number of subjects analysed
    56
    55
    55
    Units: meters (m)
        arithmetic mean (standard deviation)
    388.33 ± 69.59
    399.73 ± 68.35
    370.73 ± 93.35
    No statistical analyses for this end point

    Secondary: Change from Baseline at Week 48 in 6 Minute Walk Distance (6MWD)

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    End point title
    		 Change from Baseline at Week 48 in 6 Minute Walk Distance (6MWD)
    End point description
    The 6MWD measured the distance a participant was able to traverse while walking for 6 minutes. A longer distance reflects a better outcome. A positive change from baseline indicates an improvement. Based on the mixed-effect model of repeated measures (MMRM). ITT population included all enrolled participants who received a randomization treatment assignment. MMRM analysis included all participants at baseline and the following number of participants by Week 48: Placebo n=29, Low Dose n=25, High Dose n=31.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 48
    End point values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose
    Number of subjects analysed
    56
    55
    55
    Units: meters (m)
        least squares mean (standard error)
    -41.3 ± 8.7
    -39.6 ± 9.0
    -30.0 ± 8.7
    Statistical analysis title
    		 RO7239361 Low Dose versus Placebo
    Statistical analysis description
    Based on the MMRM using an unstructured covariance matrix -change = Baseline + Age Interactive response system (IXRS) Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.
    Comparison groups
    Placebo v RO7239361 Low Dose
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21.1
         upper limit
    		 24.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    11.5
    Statistical analysis title
    		 RO7239361 High Dose versus Placebo
    Statistical analysis description
    Based on the MMRM using an unstructured covariance matrix -change = Baseline + Age Interactive response system (IXRS) Stratum + Corticosteroid Regimen IXRS Stratum + Analysis Visit*Treatment.
    Comparison groups
    Placebo v RO7239361 High Dose
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    11.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11
         upper limit
    		 33.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    11.3

    Secondary: Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48

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    End point title
    		 Percentage of Participants for Each Clinical Global Impression of Change (CGI-C) Assessment Status at Week 48
    End point description
    The CGI-C was used to assess the participant's overall condition on a 7-point scale, using the status markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse" at Week 48 as compared to baseline. ITT population included all enrolled participants who received a randomization treatment assignment. Included in the analysis are only those subjects for whom an efficacy assessment was completed at Week 48.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 48
    End point values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose
    Number of subjects analysed
    36
    37
    31
    Units: percentage of participants
    number (not applicable)
        Very much improved
    0
    0
    0
        Much improved
    5.6
    2.7
    3.2
        Minimally improved
    13.9
    13.5
    19.4
        No change
    58.3
    54.1
    51.6
        Minimally worse
    16.7
    18.9
    22.6
        Much worse
    5.6
    10.8
    3.2
        Very much worse
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Change from Baseline at Week 48 in 95th Percentile Stride Velocity

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    End point title
    		 Change from Baseline at Week 48 in 95th Percentile Stride Velocity
    End point description
    Stride velocity was recorded with the ActiMyo device in a subset of the overall study population. The ActiMyo device measures the daily movement and activity levels of the participant. The device consists of two sensors worn on each ankle. A higher velocity reflects a better outcome. A positive change from baseline indicates an improvement. ITT population included all enrolled participants who received a randomization treatment assignment.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 48
    End point values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose
    Number of subjects analysed
    17
    19
    15
    Units: m/sec
    arithmetic mean (standard deviation)
        Baseline (n=17, 19, 15)
    1.69 ± 0.33
    1.54 ± 0.35
    1.57 ± 0.46
        Change from Baseline at Week 48 (n=5, 7, 4)
    -0.25 ± 0.39
    -0.22 ± 0.22
    -0.28 ± 0.29
    No statistical analyses for this end point

    Secondary: Number of Participants with Adverse Events (AEs)

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    End point title
    		 Number of Participants with Adverse Events (AEs)
    End point description
    An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Safety population included all enrolled participants who received at least 1 dose of study therapy. Data are presented for the arms in the DB period as wells as for RO7239361-treated arms in the whole study.
    End point type
    Secondary
    End point timeframe
    During DB period (48 weeks) and Whole study (up to approximately 38 months)
    End point values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose RO7239361 Low Dose Whole Study RO7239361 High Dose Whole Study
    Number of subjects analysed
    56
    55
    55
    69
    68
    Units: participants
    46
    48
    49
    57
    56
    No statistical analyses for this end point

    Secondary: Number of Participants with AEs Leading to Discontinuation

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    End point title
    		 Number of Participants with AEs Leading to Discontinuation
    End point description
    An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Reported here is the number of participants with AEs that led to study discontinuation. Safety population included all enrolled participants who received at least 1 dose of study therapy. Data are presented for the arms in the DB period as wells as for RO7239361-treated arms in the whole study.
    End point type
    Secondary
    End point timeframe
    During DB period (48 weeks) and Whole study (up to approximately 38 months)
    End point values
    		 Placebo RO7239361 Low Dose RO7239361 High Dose RO7239361 Low Dose Whole Study RO7239361 High Dose Whole Study
    Number of subjects analysed
    56
    55
    55
    69
    68
    Units: participants
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to approximately 38 months
    Adverse event reporting additional description
    Safety population included all enrolled participants who received at least 1 dose of study therapy.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Placebo DB
    Reporting group description
    		 Participants received matching placebo solution subcutaneously (SC) on specified days of the 48-week double-blind (DB) period.

    Reporting group title
    RO7239361 Low Dose DB
    Reporting group description
    		 Participants received low dose RO7239361 SC on specified days of the 48-week DB period.

    Reporting group title
    RO7239361 High Dose DB
    Reporting group description
    		 Participants received high dose RO7239361 SC on specified days of the 48-week DB period.

    Reporting group title
    Placebo, Then RO7239361 Low Dose OL
    Reporting group description
    		 Participants received matching placebo solution SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label (OL) period followed by 24 weeks of follow-up.

    Reporting group title
    Placebo, Then RO7239361 High Dose OL
    Reporting group description
    		 Participants received matching placebo solution SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.

    Reporting group title
    RO7239361 Low dose, Then RO7239361 Low Dose OL
    Reporting group description
    		 Participants received low dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received low dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up.

    Reporting group title
    RO7239361 High Dose, Then RO7239361 High Dose OL
    Reporting group description
    		 Participants received high dose RO7239361 SC on specified days of the 48-week DB period. Following the DB period participants received high dose RO7239361 on specified days for up to 192 weeks during the open-label period followed by 24 weeks of follow-up

    Serious adverse events
    		 Placebo DB RO7239361 Low Dose DB RO7239361 High Dose DB Placebo, Then RO7239361 Low Dose OL Placebo, Then RO7239361 High Dose OL RO7239361 Low dose, Then RO7239361 Low Dose OL RO7239361 High Dose, Then RO7239361 High Dose OL
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 56 (5.36%)
    2 / 55 (3.64%)
    4 / 55 (7.27%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         number of deaths (all causes)
    0
    0
    1
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Humerus fracture
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 55 (1.82%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 55 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Influenza like illness
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 55 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Gastrointestinal viral infection
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 55 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 55 (1.82%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypocalcaemia
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 55 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo DB RO7239361 Low Dose DB RO7239361 High Dose DB Placebo, Then RO7239361 Low Dose OL Placebo, Then RO7239361 High Dose OL RO7239361 Low dose, Then RO7239361 Low Dose OL RO7239361 High Dose, Then RO7239361 High Dose OL
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    43 / 56 (76.79%)
    43 / 55 (78.18%)
    47 / 55 (85.45%)
    8 / 14 (57.14%)
    7 / 13 (53.85%)
    13 / 24 (54.17%)
    12 / 29 (41.38%)
    Investigations
    Bone density decreased
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Glutamate dehydrogenase increased
         subjects affected / exposed
    2 / 56 (3.57%)
    1 / 55 (1.82%)
    3 / 55 (5.45%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    1
    3
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    2 / 56 (3.57%)
    5 / 55 (9.09%)
    4 / 55 (7.27%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 24 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    2
    7
    5
    0
    2
    0
    2
    Fall
         subjects affected / exposed
    5 / 56 (8.93%)
    1 / 55 (1.82%)
    5 / 55 (9.09%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    11
    1
    6
    0
    0
    0
    1
    Gadolinium deposition disease
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 55 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Ligament sprain
         subjects affected / exposed
    4 / 56 (7.14%)
    1 / 55 (1.82%)
    1 / 55 (1.82%)
    2 / 14 (14.29%)
    0 / 13 (0.00%)
    3 / 24 (12.50%)
    1 / 29 (3.45%)
         occurrences all number
    4
    2
    1
    2
    0
    3
    1
    Skin abrasion
         subjects affected / exposed
    2 / 56 (3.57%)
    3 / 55 (5.45%)
    0 / 55 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    1 / 24 (4.17%)
    1 / 29 (3.45%)
         occurrences all number
    3
    12
    0
    3
    0
    4
    1
    Thermal burn
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 55 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    9 / 56 (16.07%)
    14 / 55 (25.45%)
    10 / 55 (18.18%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    2 / 24 (8.33%)
    2 / 29 (6.90%)
         occurrences all number
    28
    60
    42
    3
    0
    9
    4
    Migraine
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 55 (1.82%)
    0 / 55 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    1 / 24 (4.17%)
    0 / 29 (0.00%)
         occurrences all number
    0
    10
    0
    1
    0
    3
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 56 (0.00%)
    4 / 55 (7.27%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    1 / 24 (4.17%)
    1 / 29 (3.45%)
         occurrences all number
    0
    4
    0
    0
    0
    1
    1
    Gait inability
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Injection site bruising
         subjects affected / exposed
    2 / 56 (3.57%)
    4 / 55 (7.27%)
    4 / 55 (7.27%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    4
    4
    0
    0
    0
    0
    Injection site erythema
         subjects affected / exposed
    8 / 56 (14.29%)
    11 / 55 (20.00%)
    12 / 55 (21.82%)
    0 / 14 (0.00%)
    3 / 13 (23.08%)
    2 / 24 (8.33%)
    1 / 29 (3.45%)
         occurrences all number
    25
    43
    38
    0
    17
    6
    1
    Injection site induration
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 55 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Injection site oedema
         subjects affected / exposed
    3 / 56 (5.36%)
    2 / 55 (3.64%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    7
    9
    9
    0
    0
    0
    0
    Injection site pruritus
         subjects affected / exposed
    0 / 56 (0.00%)
    2 / 55 (3.64%)
    2 / 55 (3.64%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    2
    6
    0
    12
    0
    0
    Injection site reaction
         subjects affected / exposed
    2 / 56 (3.57%)
    4 / 55 (7.27%)
    2 / 55 (3.64%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    29
    33
    0
    0
    0
    0
    Injection site swelling
         subjects affected / exposed
    0 / 56 (0.00%)
    4 / 55 (7.27%)
    3 / 55 (5.45%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    1 / 24 (4.17%)
    1 / 29 (3.45%)
         occurrences all number
    0
    31
    5
    0
    0
    1
    1
    Localised oedema
         subjects affected / exposed
    3 / 56 (5.36%)
    0 / 55 (0.00%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    5
    0
    1
    0
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    8 / 56 (14.29%)
    9 / 55 (16.36%)
    8 / 55 (14.55%)
    2 / 14 (14.29%)
    1 / 13 (7.69%)
    3 / 24 (12.50%)
    1 / 29 (3.45%)
         occurrences all number
    8
    13
    9
    2
    1
    3
    1
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    1 / 56 (1.79%)
    1 / 55 (1.82%)
    4 / 55 (7.27%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    1
    7
    0
    0
    0
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    1 / 56 (1.79%)
    1 / 55 (1.82%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    1
    1
    0
    1
    0
    0
    Abdominal pain
         subjects affected / exposed
    1 / 56 (1.79%)
    2 / 55 (3.64%)
    3 / 55 (5.45%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    2
    5
    0
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    3 / 56 (5.36%)
    4 / 55 (7.27%)
    7 / 55 (12.73%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    1 / 24 (4.17%)
    1 / 29 (3.45%)
         occurrences all number
    4
    5
    12
    0
    0
    1
    2
    Constipation
         subjects affected / exposed
    4 / 56 (7.14%)
    4 / 55 (7.27%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    1 / 24 (4.17%)
    0 / 29 (0.00%)
         occurrences all number
    5
    4
    1
    0
    0
    1
    0
    Diarrhoea
         subjects affected / exposed
    3 / 56 (5.36%)
    10 / 55 (18.18%)
    4 / 55 (7.27%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    1 / 24 (4.17%)
    2 / 29 (6.90%)
         occurrences all number
    3
    13
    8
    0
    0
    1
    2
    Dyspepsia
         subjects affected / exposed
    0 / 56 (0.00%)
    1 / 55 (1.82%)
    3 / 55 (5.45%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    1
    4
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    1 / 56 (1.79%)
    2 / 55 (3.64%)
    5 / 55 (9.09%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    4 / 29 (13.79%)
         occurrences all number
    1
    2
    9
    0
    0
    0
    4
    Vomiting
         subjects affected / exposed
    6 / 56 (10.71%)
    8 / 55 (14.55%)
    6 / 55 (10.91%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    3 / 24 (12.50%)
    2 / 29 (6.90%)
         occurrences all number
    6
    14
    11
    0
    0
    4
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    10 / 56 (17.86%)
    8 / 55 (14.55%)
    7 / 55 (12.73%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    10
    11
    13
    1
    0
    0
    2
    Epistaxis
         subjects affected / exposed
    3 / 56 (5.36%)
    3 / 55 (5.45%)
    6 / 55 (10.91%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    9
    15
    17
    0
    1
    0
    0
    Nasal congestion
         subjects affected / exposed
    1 / 56 (1.79%)
    3 / 55 (5.45%)
    3 / 55 (5.45%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    1
    3
    3
    1
    0
    0
    2
    Productive cough
         subjects affected / exposed
    0 / 56 (0.00%)
    3 / 55 (5.45%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    1 / 56 (1.79%)
    4 / 55 (7.27%)
    3 / 55 (5.45%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    7
    3
    2
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    3 / 56 (5.36%)
    2 / 55 (3.64%)
    1 / 55 (1.82%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    4
    2
    1
    1
    0
    0
    0
    Rash
         subjects affected / exposed
    4 / 56 (7.14%)
    4 / 55 (7.27%)
    7 / 55 (12.73%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    1 / 24 (4.17%)
    1 / 29 (3.45%)
         occurrences all number
    9
    5
    9
    0
    0
    1
    1
    Rash macular
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 55 (0.00%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Urticaria
         subjects affected / exposed
    3 / 56 (5.36%)
    2 / 55 (3.64%)
    3 / 55 (5.45%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    4
    2
    4
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    6 / 56 (10.71%)
    7 / 55 (12.73%)
    5 / 55 (9.09%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 24 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    6
    8
    6
    0
    1
    0
    1
    Back pain
         subjects affected / exposed
    4 / 56 (7.14%)
    7 / 55 (12.73%)
    2 / 55 (3.64%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    4
    9
    2
    0
    0
    0
    1
    Mobility decreased
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 55 (0.00%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    Muscle spasms
         subjects affected / exposed
    1 / 56 (1.79%)
    2 / 55 (3.64%)
    2 / 55 (3.64%)
    1 / 14 (7.14%)
    2 / 13 (15.38%)
    0 / 24 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    7
    6
    1
    2
    0
    1
    Pain in extremity
         subjects affected / exposed
    2 / 56 (3.57%)
    4 / 55 (7.27%)
    8 / 55 (14.55%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    3
    6
    11
    1
    0
    0
    0
    Infections and infestations
    Ear infection
         subjects affected / exposed
    0 / 56 (0.00%)
    4 / 55 (7.27%)
    1 / 55 (1.82%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    0
    4
    2
    1
    0
    0
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 56 (1.79%)
    1 / 55 (1.82%)
    3 / 55 (5.45%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    1
    5
    0
    0
    0
    0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 56 (1.79%)
    1 / 55 (1.82%)
    1 / 55 (1.82%)
    1 / 14 (7.14%)
    0 / 13 (0.00%)
    1 / 24 (4.17%)
    0 / 29 (0.00%)
         occurrences all number
    1
    1
    1
    1
    0
    1
    0
    Hordeolum
         subjects affected / exposed
    0 / 56 (0.00%)
    2 / 55 (3.64%)
    0 / 55 (0.00%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 24 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    0
    2
    0
    0
    1
    0
    1
    Influenza
         subjects affected / exposed
    3 / 56 (5.36%)
    6 / 55 (10.91%)
    1 / 55 (1.82%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    2 / 24 (8.33%)
    0 / 29 (0.00%)
         occurrences all number
    3
    6
    1
    0
    0
    2
    0
    Nasopharyngitis
         subjects affected / exposed
    13 / 56 (23.21%)
    13 / 55 (23.64%)
    13 / 55 (23.64%)
    2 / 14 (14.29%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    17
    17
    16
    2
    0
    0
    2
    Pharyngitis
         subjects affected / exposed
    2 / 56 (3.57%)
    2 / 55 (3.64%)
    3 / 55 (5.45%)
    0 / 14 (0.00%)
    1 / 13 (7.69%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    2
    2
    3
    0
    1
    0
    0
    Rhinitis
         subjects affected / exposed
    1 / 56 (1.79%)
    3 / 55 (5.45%)
    4 / 55 (7.27%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    5
    7
    0
    0
    0
    0
    Sinusitis
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 55 (0.00%)
    3 / 55 (5.45%)
    0 / 14 (0.00%)
    0 / 13 (0.00%)
    0 / 24 (0.00%)
    0 / 29 (0.00%)
         occurrences all number
    1
    0
    4
    0
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 56 (10.71%)
    4 / 55 (7.27%)
    7 / 55 (12.73%)
    1 / 14 (7.14%)
    1 / 13 (7.69%)
    0 / 24 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    8
    5
    16
    1
    1
    0
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Apr 2017
    V1: Added text defining significant change in dosage for prednisone and deflazacort. Added measurement of ulna length to baseline and on treatment time points. Timing of on treatment videotaping of functional assessments was clarified. Timing of Health Care Resource Utilization assessments was clarified. Added clarification that DXA scanning is not required at early termination. History of hypersensitivity of the components of the study drug added as an exclusion. Threshold for adjusting dosing weight tier increased from 1 kg to 2 kg. Text clarifying that malfunctions of pre-filled syringes should be reported to the sponsor in accordance with local regulations has been added. Guidance regarding skin biopsy added. Text describing pharmacogenomics removed.
    21 Aug 2017
    V2: Changed Sponsor from Bristol-Myers Squibb to F. Hoffmann-La Roche Ltd. Changed study drug name from BMS-986089 to RO7239361.
    29 Jan 2018
    V3: Added assessment of CGI-C. Reduced pulmonary function tests. Reduced anthropometry assessments. Reduced myometry assessments. Reduced timed function tests (TFTs) and 6 minute walk test (6MWT) in the open-label phases. Clarified forced vital capacity (FVC) in the exclusion criteria. Clarified contraception methods. Clarified GDF-11 sample timepoint. Clarified ActiMyo assessments. Clarified use of videos. Updated requirement for safety reporting of overdose. Clarified monitoring of anti-drug antibodies (ADAs) during 24-week safety follow-up phase.
    16 Aug 2018
    V4: Deleted references to the previous Bristol-Myers Squibb protocol and product numbers throughout most of the text. Changed the primary endpoint from the 4 Stair Climb velocity (4SCV) to the North Star Ambulatory Assessment total score. Added a new inclusion criterion requiring a minimum NSAA score of 15 points at screening. Changed the 4SCV from the primary endpoint to a secondary endpoint. Added 95th percentile stride velocity, as recorded using the ActiMyo as a secondary endpoint. Updated the duration of the open-label (OL) extension phase and the frequency of visits during the OL extension phase. Added the specific sites indicated for subcutaneous injection. Deleted the proposed interim analysis. Updated the statistical analysis section to establish hierarchical testing of the doses. Added definitions for different situations of incorrect administration of study drug.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    28 Apr 2020
    The study was terminated early as a pre-planned futility analysis indicated lack of efficacy.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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