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    Clinical Trial Results:
    Multicenter, Open-Label, Single-Arm Study to Evaluate Long-Term Safety, Tolerability, and Effectiveness of 10 mg/kg BID Olesoxime in Patients With Spinal Muscular Atrophy

    Summary
    EudraCT number
    		 2015-001589-25
    Trial protocol
    		 GB   IT   DE   BE   NL   FR   PL  
    Global end of trial date
    18 Dec 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    22 Jun 2019
    First version publication date
    22 Jun 2019
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    BN29854
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02628743
    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)
    No
    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
    01 May 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    18 Dec 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Dec 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The main objective of this open-label, single arm study is to further characterize the safety, tolerability and effectiveness profile of olesoxime in Spinal Muscular Atrophy (SMA).
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    20 Jan 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 14
    Country: Number of subjects enrolled
    Belgium: 14
    Country: Number of subjects enrolled
    France: 28
    Country: Number of subjects enrolled
    Germany: 10
    Country: Number of subjects enrolled
    Italy: 39
    Country: Number of subjects enrolled
    Netherlands: 6
    Country: Number of subjects enrolled
    Poland: 20
    Worldwide total number of subjects
    131
    EEA total number of subjects
    131
    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)
    56
    Adolescents (12-17 years)
    36
    Adults (18-64 years)
    39
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 131 patients were screened and enrolled into the study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Olesoxime
    Arm description
    		 Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Olesoxime
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for oral suspension
    Routes of administration
    Nasogastric use , Oral use, Gastroenteral use
    Dosage and administration details
    Participant will receive 10 milligrams per kilogram (mg/kg) suspension once a day orally or via a naso-gastric or gastronomy tube. Participants who had consented to the dose increase also received 10 mg/kg suspension twice a day (BID).

    Number of subjects in period 1
    		Olesoxime
    Started
    131
    Completed
    0
    Not completed
    131
         Consent withdrawn by subject
    50
         Physician decision
    2
         Not Available
    3
         Study Terminated by Sponsor
    76

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Olesoxime
    Reporting group description
    		 Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.

    Reporting group values
    		 Olesoxime Total
    Number of subjects
    		 131 131
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 56 56
        Adolescents (12-17 years)
    		 36 36
        Adults (18-64 years)
    		 39 39
        From 65-84 years
    		 0 0
        85 years and over
    		 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 14.7 ± 5.9 -
    Sex: Female, Male
    Units: Subjects
        Female
    		 66 66
        Male
    		 65 65
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0
        Asian
    		 3 3
        Native Hawaiian or Other Pacific Islander
    		 0 0
        Black or African American
    		 1 1
        White
    		 94 94
        More than one race
    		 0 0
        Unknown or Not Reported
    		 33 33
    Race/Ethnicity, Customized
    Units: Subjects
        Hispanic or Latino
    		 1 1
        Not Hispanic or Latino
    		 89 89
        Not Stated
    		 29 29
        Unknown
    		 12 12

    End points

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    End points reporting groups
    Reporting group title
    Olesoxime
    Reporting group description
    		 Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.

    Primary: Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)

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    End point title
    		 Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) [1]
    End point description
    End point type
    Primary
    End point timeframe
    Baseline up to approximately 3 years
    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 analyses were defined for this endpoint.
    End point values
    		 Olesoxime
    Number of subjects analysed
    131
    Units: percentage of participants
    number (not applicable)
        SAEs
    27.5
        AEs
    91.6
    No statistical analyses for this end point

    Secondary: Change From Baseline in Motor Function Measure (MFM) Dimension 1 (D1) + Dimension 2 (D2) Score

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    End point title
    		 Change From Baseline in Motor Function Measure (MFM) Dimension 1 (D1) + Dimension 2 (D2) Score
    End point description
    The MFM scale evaluated motor function in three dimensions. D1 evaluates functions related to standing and transfer, D2 evaluates axial and proximal function in supine and sitting position on mat and chair and D3 evaluates distal motor function. The scoring of each task uses a 4-point Likert scale based on the participant’s maximal abilities without assistance: 0, cannot initiate the task or maintain the starting position; 1, performs the task partially; 2, performs the task incompletely or imperfectly (with compensatory/uncontrolled movements or slowness); and 3, performs the task fully and “normally”. The score is expressed as a percentage of the maximum possible score. The lower the total score, the more severe the impairment.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: score on scale
    arithmetic mean (standard deviation)
        Baseline (n=127)
    30.01 ± 12.77
        Week 26 (n=127)
    -0.06 ± 4.75
        Week 52 (n=111)
    -0.31 ± 4.61
        Week 78 (n=112)
    -1.26 ± 5.64
        Week 104 (n=99)
    -3.32 ± 7.08
        Week 130 (n=64)
    -4.87 ± 9.91
    No statistical analyses for this end point

    Secondary: Change From Baseline in MFM Total Score (D1+ D2 + Dimension 3 [D3]) Score

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    End point title
    		 Change From Baseline in MFM Total Score (D1+ D2 + Dimension 3 [D3]) Score
    End point description
    The MFM scale evaluated motor function in three dimensions. D1 evaluates functions related to standing and transfer, D2 evaluates axial and proximal function in supine and sitting position on mat and chair and D3 evaluates distal motor function. The scoring of each task uses a 4-point Likert scale based on the participant’s maximal abilities without assistance: 0, cannot initiate the task or maintain the starting position; 1, performs the task partially; 2, performs the task incompletely or imperfectly (with compensatory/uncontrolled movements or slowness); and 3, performs the task fully and “normally”. The score is expressed as a percentage of the maximum possible score. The lower the total score, the more severe the impairment.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: score on scale
    arithmetic mean (standard deviation)
        Baseline (n=127)
    41.21 ± 12.81
        Week 26 (n=127)
    0.31 ± 4.35
        Week 52 (n=111)
    0.08 ± 4.08
        Week 78 (n=112)
    -0.64 ± 5.28
        Week 104 (n=99)
    -2.96 ± 7.09
        Week 130 (n=64)
    -4.02 ± 9.48
    No statistical analyses for this end point

    Secondary: Plasma Concentrations of Olesoxime

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    End point title
    		 Plasma Concentrations of Olesoxime
    End point description
    Values are reported separately for QD and BID doses. Dose increase occurred after Week 104.
    End point type
    Secondary
    End point timeframe
    Pre-dose (Hour 0) at Weeks 1, 13, 26, 39, 52, 78, 104 and 130
    End point values
    		 Olesoxime
    Number of subjects analysed
    131
    Units: ng/mL
    arithmetic mean (standard deviation)
        Baseline (n=128)
    129.0 ± 160.2
        Week 13 (n=128)
    9475.5 ± 3962.5
        Week 26 (n=119)
    10021.3 ± 4885.6
        Week 39 (n=117)
    10257.8 ± 4443.7
        Week 52 (n=112)
    9665.6 ± 4941.8
        Week 78 (n=107)
    10351.4 ± 5267.3
        Week 104 (n=100)
    8566.4 ± 5353.1
        Dose Increase Visit (BID) (n=19)
    14797.1 ± 5773.8
        Week 130 (QD) (n=46)
    6274.6 ± 6281.9
        Week 130 (BID) (n=20)
    13956.9 ± 9565.0
    No statistical analyses for this end point

    Secondary: Change from Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score

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    End point title
    		 Change from Baseline in Pediatric Quality of Life Questionnaire (PedsQL) Generic Core Scale Version 4.0 Score
    End point description
    The PedsQL Generic Core Scale includes 23 items using self-report and/or parent report (ages 5+). The instrument covers physical, emotional, social and school functioning. Scale items are linearly transformed to a 0–100 scale (0 = 100, 1 = 75, 2 = 50, 3 = 25, and 4 = 0) so that higher scores indicate better health related quality of life.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: score on scale
    arithmetic mean (standard deviation)
        Baseline (Total Score) (n=128)
    58.69 ± 11.17
        Total Score - Week 26 (n=126)
    -0.80 ± 9.10
        Total Score - Week 52 (n=118)
    -1.33 ± 10.52
        Total Score - Week 78 (n=109)
    -0.72 ± 10.98
        Total Score - Week 104 (n=101)
    -0.35 ± 11.69
        Total Score - Week 130 (n=67)
    -0.11 ± 10.83
        Baseline (Physical Score) (n=128)
    28.49 ± 16.50
        Physical Score - Week 26 (n=126)
    -1.76 ± 15.99
        Physical Score - Week 52 (n=117)
    -4.48 ± 17.68
        Physical Score - Week 78 (n=109)
    -3.18 ± 19.67
        Physical Score - Week 104 (n=101)
    -1.42 ± 17.87
        Physical Score - Week 130 (n=67)
    -3.23 ± 16.33
        Baseline (Emotional Score) (n=128)
    74.61 ± 17.34
        Emotional Score - Week 26 (n=126)
    -1.19 ± 18.62
        Emotional Score - Week 52 (n=118)
    1.19 ± 16.27
        Emotional Score - Week 78 (n=108)
    -0.05 ± 17.23
        Emotional Score - Week 104 (n=101)
    -0.54 ± 18.37
        Emotional Score - Week 130 (n=67)
    2.31 ± 18.47
        Baseline (Social Score) (n=128)
    72.77 ± 18.59
        Social Score - Week 26 (n=126)
    1.43 ± 14.15
        Social Score - Week 52 (n=118)
    0.93 ± 15.91
        Social Score - Week 78 (n=109)
    2.39 ± 17.38
        Social Score - Week 104 (n=101)
    2.38 ± 18.62
        Social Score - Week 130 (n=67)
    4.10 ± 16.05
        Baseline (School/Work Score) (n=127)
    77.20 ± 15.83
        School/Work Score - Week 26 (n=125)
    -1.24 ± 14.28
        School/Work Score - Week 52 (n=117)
    -1.32 ± 14.09
        School/Work Score - Week 78 (n=107)
    -0.51 ± 14.26
        School/Work Score - Week 104 (n=100)
    -1.65 ± 15.24
        School/Work Score - Week 130 (n=66)
    -2.58 ± 15.04
    No statistical analyses for this end point

    Secondary: Change from Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score

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    End point title
    		 Change from Baseline in Caregiver PedsQL Generic Core Scales Version 4.0 Score
    End point description
    The PedsQL Generic Core Scale includes 23 items. The instrument covers physical, emotional, social and school functioning. Scale items are linearly transformed to a 0–100 scale (0 = 100, 1 = 75, 2 = 50, 3 = 25, and 4 = 0) so that higher scores indicate better health related quality of life. Questionnaire was completed by the caregiver.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: score on scale
    arithmetic mean (standard deviation)
        Baseline (Total Score) (n=121)
    55.58 ± 12.49
        Total Score - Week 26 (n=115)
    -0.85 ± 13.15
        Total Score - Week 52 (n=106)
    -1.86 ± 13.12
        Total Score - Week 78 (n=103)
    -0.67 ± 13.88
        Total Score - Week 104 (n=93)
    -1.64 ± 17.95
        Total Score - Week 130 (n=62)
    -0.33 ± 13.41
        Baseline (Physical Score) (n=121)
    28.99 ± 25.84
        Physical Score - Week 26 (n=115)
    -0.58 ± 28.66
        Physical Score - Week 52 (n=106)
    -5.10 ± 25.86
        Physical Score - Week 78 (n=103)
    -2.91 ± 28.91
        Physical Score - Week 104 (n=93)
    -3.28 ± 34.80
        Physical Score - Week 130 (n=62)
    -0.56 ± 30.09
        Baseline (Emotional Score) (n=121)
    67.48 ± 17.31
        Emotional Score - Week 26 (n=115)
    -2.13 ± 15.30
        Emotional Score - Week 52 (n=106)
    -0.90 ± 15.08
        Emotional Score - Week 78 (n=103)
    -0.39 ± 18.81
        Emotional Score - Week 104 (n=93)
    -0.70 ± 20.54
        Emotional Score - Week 130 (n=62)
    -0.32 ± 15.94
        Baseline (Social Score) (n=121)
    68.34 ± 16.19
        Social Score - Week 26 (n=115)
    -0.42 ± 16.84
        Social Score - Week 52 (n=106)
    -0.49 ± 15.92
        Social Score - Week 78 (n=103)
    1.47 ± 18.40
        Social Score - Week 104 (n=93)
    -0.55 ± 21.72
        Social Score - Week 130 (n=61)
    1.25 ± 16.22
        Baseline (School/Work Score) (n=120)
    73.67 ± 17.69
        School/Work Score - Week 26 (n=112)
    -0.31 ± 16.69
        School/Work Score - Week 52 (n=104)
    0.53 ± 18.14
        School/Work Score - Week 78 (n=101)
    0.94 ± 18.39
        School/Work Score - Week 104 (n=91)
    -0.71 ± 20.64
        School/Work Score - Week 130 (n=59)
    -1.53 ± 16.17
    No statistical analyses for this end point

    Secondary: Change from Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score

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    End point title
    		 Change from Baseline in PedsQL Neuromuscular Module Version 3.0 Scale Score
    End point description
    The PedsQL Neuromuscular Module (Version 3.0) includes 25 items using self-report (ages 5 - 18) and/or parent report (ages 5 -18). The instrument covers problems related to neuromuscular disease, communication and family resources. Scale items are linearly transformed to a 0–100 scale (0 = 100, 1 = 75, 2 = 50, 3 = 25, and 4 = 0) so that higher scores indicate better health related quality of life.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: score on scale
    arithmetic mean (standard deviation)
        Baseline (Total Score) (n=90)
    69.57 ± 14.01
        Total Score - Week 26 (n=89)
    -0.98 ± 10.75
        Total Score - Week 52 (n=81)
    -0.86 ± 12.81
        Total Score - Week 78 (n=79)
    -1.08 ± 12.11
        Total Score - Week 104 (n=70)
    -1.18 ± 13.13
        Total Score - Week 130 (n=52)
    -1.41 ± 12.61
        Baseline (Neuromuscular) (n=90)
    66.03 ± 15.39
        Neuromuscular - Week 26 (n=89)
    -1.77 ± 12.28
        Neuromuscular - Week 52 (n=81)
    -2.22 ± 14.29
        Neuromuscular - Week 78 (n=79)
    -2.69 ± 12.82
        Neuromuscular - Week 104 (n=70)
    -1.90 ± 15.11
        Neuromuscular - Week 130 (n=52)
    -3.14 ± 14.20
        Baseline (Family Resources Score) (n=90)
    74.39 ± 20.10
        Family Resources Score - Week 26 (n=89)
    -0.11 ± 17.35
        Family Resources Score - Week 52 (n=80)
    1.78 ± 16.07
        Family Resources Score - Week 78 (n=79)
    0.82 ± 19.22
        Family Resources Score - Week 104 (n=70)
    -1.29 ± 19.81
        Family Resources Score - Week 130 (n=52)
    -0.38 ± 16.36
        Baseline (Communication Score) (n=90)
    81.57 ± 21.14
        Communication Score - Week 26 (n=89)
    2.01 ± 19.86
        Communication Score - Week 52 (n=81)
    1.44 ± 24.43
        Communication Score - Week 78 (n=79)
    4.85 ± 22.19
        Communication Score - Week 104 (n=70)
    2.98 ± 24.25
        Communication Score - Week 130 (n=52)
    6.57 ± 25.15
    No statistical analyses for this end point

    Secondary: Change from Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score

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    End point title
    		 Change from Baseline in Caregiver PedsQL Neuromuscular Module Version 3.0 Scale Score
    End point description
    The PedsQL Neuromuscular Module (Version 3.0) includes 25 items using self-report (ages 5 - 18) and/or parent report (ages 5 -18). The instrument covers problems related to neuromuscular disease, communication and family resources. Scale items are linearly transformed to a 0–100 scale (0 = 100, 1 = 75, 2 = 50, 3 = 25, and 4 = 0) so that higher scores indicate better health related quality of life. Questionnaire was completed by the caregiver.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: score on scale
    arithmetic mean (standard deviation)
        Baseline (Total Score) (n=88)
    59.44 ± 14.83
        Total Score - Week 26 (n=87)
    0.13 ± 10.12
        Total Score - Week 52 (n=78)
    -0.11 ± 12.89
        Total Score - Week 78 (n=77)
    0.65 ± 13.23
        Total Score - Week 104 (n=67)
    1.21 ± 14.40
        Total Score - Week 130 (n=51)
    -0.07 ± 12.86
        Baseline (Neuromuscular) (n=88)
    56.28 ± 15.70
        Neuromuscular - Week 26 (n=87)
    -0.64 ± 10.92
        Neuromuscular - Week 52 (n=78)
    -1.33 ± 13.39
        Neuromuscular - Week 78 (n=77)
    0.05 ± 13.97
        Neuromuscular - Week 104 (n=67)
    0.54 ± 15.32
        Neuromuscular - Week 130 (n=51)
    -1.39 ± 14.65
        Baseline (Family Resources Score) (n=88)
    58.24 ± 25.08
        Family Resources Score - Week 26 (n=86)
    1.74 ± 16.57
        Family Resources Score - Week 52 (n=77)
    2.44 ± 19.04
        Family Resources Score - Week 78 (n=77)
    0.91 ± 19.31
        Family Resources Score - Week 104 (n=67)
    1.27 ± 18.63
        Family Resources Score - Week 130 (n=50)
    1.00 ± 17.26
        Baseline (Communication Score) (n=88)
    79.36 ± 22.92
        Communication Score - Week 26 (n=87)
    1.92 ± 20.08
        Communication Score - Week 52 (n=78)
    2.88 ± 22.31
        Communication Score - Week 78 (n=77)
    3.57 ± 20.92
        Communication Score - Week 104 (n=67)
    4.85 ± 24.24
        Communication Score - Week 130 (n=51)
    4.90 ± 22.74
    No statistical analyses for this end point

    Secondary: Change from Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire Index Score - Total Score

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    End point title
    		 Change from Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire Index Score - Total Score
    End point description
    The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 1), Weeks 26, 52, 78, 104, 130; thereafter every 26 weeks up to 5 years
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: score on scale
    arithmetic mean (standard deviation)
        Baseline (n=74)
    0.0471 ± 0.1345
        Week 26 (n=72)
    0.0084 ± 0.1563
        Week 52 (n=68)
    -0.0164 ± 0.1191
        Week 78 (n=66)
    0.0168 ± 0.1910
        Week 104 (n=57)
    0.0081 ± 0.1701
        Week 130 (n=34)
    -0.0259 ± 0.1232
    No statistical analyses for this end point

    Secondary: Change from Baseline in Caregiver Proxy EQ-5D-5L Questionnaire Index Score - Total Score

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    End point title
    		 Change from Baseline in Caregiver Proxy EQ-5D-5L Questionnaire Index Score - Total Score
    End point description
    The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction. The questionnaire was completed by the caregiver.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 1), Weeks 26, 52, 78, 104, 130; thereafter every 26 weeks up to 5 years
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: score on scale
    arithmetic mean (standard deviation)
        Baseline (n=54)
    0.0429 ± 0.2335
        Week 26 (n=50)
    0.0652 ± 0.4091
        Week 52 (n=47)
    0.0203 ± 0.2820
        Week 78 (n=47)
    0.0696 ± 0.3094
        Week 104 (n=39)
    0.0699 ± 0.2887
        Week 130 (n=31)
    0.0455 ± 0.3323
    No statistical analyses for this end point

    Secondary: Change from Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score

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    End point title
    		 Change from Baseline in EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) Score
    End point description
    The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 1), Weeks 26, 52, 78, 104, 130; thereafter every 26 weeks up to 5 years
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: score on scale
    arithmetic mean (standard deviation)
        Baseline (n=75)
    69.4 ± 19.7
        Week 26 (n=73)
    1.3 ± 17.1
        Week 52 (n=69)
    0.2 ± 17.4
        Week 78 (n=67)
    1.3 ± 19.9
        Week 104 (n=58)
    5.4 ± 17.0
        Week 130 (n=35)
    0.6 ± 18.1
    No statistical analyses for this end point

    Secondary: Change from Baseline in Caregiver Proxy EQ-5D-5L VAS Score

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    End point title
    		 Change from Baseline in Caregiver Proxy EQ-5D-5L VAS Score
    End point description
    The EQ-5D-5L is a self-reported health status questionnaire that consists of six questions used to calculate a health utility score for use in health economic analysis. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. Questionnaire was completed by the caregiver.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 1), Weeks 26, 52, 78, 104, 130; thereafter every 26 weeks up to 5 years
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: score on scale
    arithmetic mean (standard deviation)
        Baseline (n=54)
    72.7 ± 21.4
        Week 26 (n=49)
    -0.3 ± 27.7
        Week 52 (n=47)
    0.8 ± 21.2
        Week 78 (n=47)
    0.4 ± 20.9
        Week 104 (n=40)
    5.7 ± 24.3
        Week 130 (n=31)
    0.5 ± 17.9
    No statistical analyses for this end point

    Secondary: Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) Questionnaire

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    End point title
    		 Number of Subjects Employed Assessed Using the Work Productivity and Activity Impairment Questionnaire: Caregiver (WPAI:CG) Questionnaire
    End point description
    The WPAI:CG consists of four questions about the effects of Spinal Muscular Atrophy (SMA) on the following: employment status, hours missed due to patient caregiving, hours missed due to other reasons, hours actually worked and two questions that measure the degree to which patient caregiving affected productivity and regular daily activities.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: participants
        Baseline (n=121)
    56
        Week 26 (n=119)
    66
        Week 52 (n=109)
    58
        Week 78 (n=107)
    62
        Week 104 (n=97)
    56
        Week 130 (n=65)
    39
    No statistical analyses for this end point

    Secondary: Change from Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire

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    End point title
    		 Change from Baseline in Hours Actually Worked and Work Hours Missed Assessed Using WPAI:CG Questionnaire
    End point description
    The WPAI:CG consists of four questions about the effects of SMA on the following: employment status, hours missed due to patient caregiving (HMC), hours missed due to other reasons (HMO), hours actually worked (HAW) and two questions that measure the degree to which patient caregiving affected productivity and regular daily activities.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: hours
    arithmetic mean (standard deviation)
        Baseline (HMC) (n=56)
    2.0 ± 3.7
        HMC, Week 26 (n=50)
    2.0 ± 7.3
        HMC, Week 52 (n=44)
    1.9 ± 8.2
        HMC, Week 78 (n=49)
    0.9 ± 5.6
        HMC, Week 104 (n=45)
    3.2 ± 8.3
        HMC, Week 130 (n=35)
    1.1 ± 8.1
        Baseline (HMO) (n=56)
    4.8 ± 7.3
        HMO, Week 26 (n=51)
    -1.5 ± 7.9
        HMO, Week 52 (n=43)
    -1.5 ± 9.0
        HMO, Week 78 (n=49)
    -0.1 ± 8.6
        HMO, Week 104 (n=45)
    0.0 ± 9.6
        HMO, Week 130 (n=35)
    0.8 ± 7.8
        Baseline (HAW) (n=56)
    36.0 ± 47.0
        HAW, Week 26 (n=51)
    -12.0 ± 46.7
        HAW, Week 52 (n=43)
    -8.3 ± 49.2
        HAW, Week 78 (n=48)
    -8.6 ± 49.8
        HAW, Week 104 (n=44)
    1.2 ± 14.4
        HAW, Week 130 (n=35)
    1.5 ± 27.5
    No statistical analyses for this end point

    Secondary: Change from Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score

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    End point title
    		 Change from Baseline in Work Time Missed, Impairment While Working, Overall Work Impairment and Activity Impairment Assessed Using WPAI:CG Questionnaire Score
    End point description
    The WPAI:CG consists of four questions about the effects of Spinal Muscular Atrophy (SMA) on the following: employment status, hours missed due to patient caregiving, hours missed due to other reasons, hours actually worked and two questions that measure the degree to which patient caregiving affected productivity and regular daily activities. WPAI:CG outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. The outcomes are presented for Percent work time missed (WTM), Percent impairment (IMP), Percent overall work impairment (OWI) and Percent activity impairment (AIM).
    End point type
    Secondary
    End point timeframe
    Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: percentage
    arithmetic mean (standard deviation)
        Baseline (WTM) (n=53)
    6.7 ± 11.9
        WTM, Week 26 (n=44)
    7.0 ± 22.3
        WTM, Week 52 (n=38)
    0.8 ± 15.4
        WTM, Week 78 (n=43)
    6.2 ± 23.3
        WTM, Week 104 (n=39)
    6.7 ± 20.1
        WTM, Week 130 (n=31)
    4.7 ± 24.4
        Baseline (IMP) (n=56)
    29.3 ± 26.6
        IMP, Week 26 (n=50)
    -3.0 ± 22.8
        IMP, Week 52 (n=46)
    -1.5 ± 27.3
        IMP, Week 78 (n=49)
    -3.5 ± 25.0
        IMP, Week 104 (n=45)
    0.7 ± 22.8
        IMP, Week 130 (n=35)
    -6.9 ± 24.7
        Baseline (OWI) (n=53)
    33.8 ± 28.1
        OWI, Week 26 (n=43)
    -3.6 ± 25.3
        OWI, Week 52 (n=38)
    -3.3 ± 25.4
        OWI, Week 78 (n=43)
    -3.0 ± 31.9
        OWI, Week 104 (n=39)
    3.5 ± 26.2
        OWI, Week 130 (n=31)
    -3.4 ± 33.3
        Baseline (AIM) (n=121)
    45.8 ± 29.3
        AIM, Week 26 (n=114)
    -3.9 ± 28.7
        AIM, Week 52 (n=106)
    -1.3 ± 30.6
        AIM, Week 78 (n=105)
    -6.3 ± 32.6
        AIM, Week 104 (n=94)
    -7.6 ± 27.8
        AIM, Week 130 (n=64)
    -5.5 ± 31.7
    No statistical analyses for this end point

    Secondary: Change from Baseline in Degree Patient Caregiving Affected Productivity and Activities Using WPAI:CG Questionnaire

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    End point title
    		 Change from Baseline in Degree Patient Caregiving Affected Productivity and Activities Using WPAI:CG Questionnaire
    End point description
    The WPAI:CG consists of four questions about the effects of Spinal Muscular Atrophy (SMA) on the following: employment status, hours missed due to patient caregiving, hours missed due to other reasons, hours actually worked and two questions that measure the degree to which patient caregiving affected productivity and regular daily activities. WPAI:CG outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: percentage
    arithmetic mean (standard deviation)
        Baseline (Productivity) (n=56)
    29.3 ± 26.6
        Productivity, Week 26 (n=50)
    -3.0 ± 22.8
        Productivity, Week 52 (n=46)
    -1.5 ± 27.3
        Productivity, Week 78 (n=49)
    -3.5 ± 25.0
        Productivity, Week 104 (n=45)
    0.7 ± 22.8
        Productivity, Week 130 (n=35)
    -6.9 ± 24.7
        Baseline (Activities) (n=121)
    45.8 ± 29.3
        Activities, Week 26 (n=114)
    -3.9 ± 28.7
        Activities, Week 52 (n=106)
    -1.3 ± 30.6
        Activities, Week 78 (n=105)
    -6.3 ± 32.6
        Activities, Week 104 (n=94)
    -7.6 ± 27.8
        Activities, Week 130 (n=64)
    -5.5 ± 31.7
    No statistical analyses for this end point

    Secondary: Change from Baseline in Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS): Caregiver

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    End point title
    		 Change from Baseline in Short-Form 36 (SF-36) Physical Composite Scores (PCS) and Mental Composite Scores (MCS): Caregiver
    End point description
    The SF-36 was used to assess health-related quality of life at baseline and at on-treatment visits. The SF-36 consisted of 36 questions covering 8 domains (physical functioning, role-functioning physical, bodily pain, general health, vitality, social functioning, role-functioning emotional and mental health), with each domain scoring on a scale 0-100 (a score of 0 = maximum disability and a score of 100 = no disability). The 8 domains are further summarized to 2 distinct higher-ordered clusters: the physical and mental composite t-scores (PCS and MCS). The range for all 8 domains as well as for the composite norm-based t-scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status. Reported here are the Physical Composite Scores (PCS) and Mental Composite Scores (MCS).
    End point type
    Secondary
    End point timeframe
    Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: score on scale
    arithmetic mean (standard deviation)
        Baseline (PCS) (n=99)
    48.07 ± 10.33
        PCS, Week 26 (n=95)
    -0.24 ± 10.95
        PCS, Week 52 (n=87)
    0.27 ± 9.73
        PCS, Week 78 (n=88)
    -0.34 ± 10.87
        PCS, Week 104 (n=77)
    -0.48 ± 10.30
        PCS, Week 130 (n=56)
    1.68 ± 12.94
        Baseline (MCS) (n=101)
    49.71 ± 10.52
        MCS, Week 26 (n=97)
    -1.05 ± 10.22
        MCS, Week 52 (n=89)
    -1.64 ± 10.06
        MCS, Week 78 (n=90)
    -0.21 ± 9.30
        MCS, Week 104 (n=79)
    -0.08 ± 7.73
        MCS, Week 130 (n=57)
    -1.21 ± 9.98
    No statistical analyses for this end point

    Secondary: Change from Baseline in SF-36 Domain Scores: Caregiver

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    End point title
    		 Change from Baseline in SF-36 Domain Scores: Caregiver
    End point description
    The SF-36 was used to assess health-related quality of life at baseline and at on-treatment visits. The SF-36 consisted of 36 questions covering 8 domains (physical functioning, role-functioning physical, bodily pain, general health, vitality, social functioning, role-functioning emotional and mental health), with each domain scoring on a scale 0-100 (a score of 0 = maximum disability and a score of 100 = no disability). The range for all 8 norm-based domains was from 0 to 100 with 100 as best possible health status and 0 as worst health status.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: score on scale
    arithmetic mean (standard deviation)
        Baseline (Physical) (n=99)
    44.51 ± 15.97
        Physical, Week 26 (n=95)
    1.73 ± 16.36
        Physical, Week 52 (n=87)
    2.03 ± 14.23
        Physical, Week 78 (n=88)
    1.25 ± 16.16
        Physical, Week 104 (n=77)
    2.39 ± 16.61
        Physical, Week 130 (n=56)
    6.02 ± 18.87
        Baseline (Role (Physical)) (n=101)
    47.95 ± 8.83
        Role (physical), Week 26 (n=97)
    -1.18 ± 10.29
        Role (physical), Week 52 (n=89)
    -0.76 ± 9.45
        Role (physical), Week 78 (n=90)
    -1.02 ± 9.82
        Role (physical), Week 104 (n=79)
    -1.05 ± 8.92
        Role (physical), Week 130 (n=57)
    -0.35 ± 10.75
        Baseline (Bodily pain) (n=101)
    50.94 ± 8.77
        Bodily pain, Week 26 (n=97)
    -1.82 ± 8.75
        Bodily pain, Week 52 (n=89)
    -1.83 ± 9.04
        Bodily pain, Week 78 (n=90)
    -2.14 ± 10.55
        Bodily pain, Week 104 (n=79)
    -2.40 ± 8.44
        Bodily pain, Week 130 (n=57)
    -2.96 ± 9.82
        Baseline (General health) (n=101)
    50.21 ± 10.65
        General health, Week 26 (n=97)
    -0.63 ± 10.59
        General health, Week 52 (n=89)
    -0.75 ± 9.64
        General health, Week 78 (n=90)
    -0.22 ± 10.83
        General health, Week 104 (n=79)
    -1.17 ± 11.22
        General health, Week 130 (n=57)
    1.07 ± 11.87
        Baseline (Vitality) (n=101)
    51.28 ± 9.42
        Vitality, Week 26 (n=97)
    -1.04 ± 8.48
        Vitality, Week 52 (n=89)
    -1.23 ± 7.53
        Vitality, Week 78 (n=90)
    -0.03 ± 9.67
        Vitality, Week 104 (n=79)
    -0.07 ± 8.16
        Vitality, Week 130 (n=57)
    0.37 ± 8.57
        Baseline (Social) (n=101)
    48.01 ± 9.49
        Social, Week 26 (n=97)
    -0.67 ± 10.60
        Social, Week 52 (n=89)
    -1.24 ± 11.14
        Social, Week 78 (n=90)
    0.28 ± 10.29
        Social, Week 104 (n=79)
    -0.95 ± 9.12
        Social, Week 130 (n=57)
    0.35 ± 10.46
        Baseline (Role (emotional)) (n=101)
    48.38 ± 9.58
        Role (emotional), Week 26 (n=97)
    -1.15 ± 10.59
        Role (emotional), Week 52 (n=89)
    -1.72 ± 11.38
        Role (emotional), Week 78 (n=90)
    -1.16 ± 10.58
        Role (emotional), Week 104 (n=79)
    -1.06 ± 8.03
        Role (emotional), Week 130 (n=57)
    -0.43 ± 9.87
        Baseline (Mental health) (n=101)
    48.46 ± 9.39
        Mental health, Week 26 (n=97)
    -0.24 ± 9.73
        Mental health, Week 52 (n=89)
    -0.50 ± 9.15
        Mental health, Week 78 (n=90)
    0.07 ± 7.77
        Mental health, Week 104 (n=79)
    1.32 ± 7.42
        Mental health, Week 130 (n=57)
    -0.29 ± 9.21
    No statistical analyses for this end point

    Secondary: Change from Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver

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    End point title
    		 Change from Baseline in Revised Utility Index Score (SF-6D_R2): Caregiver
    End point description
    The SF-6D focuses on seven of the eight health domains covered by the SF-36: physical functioning, role participation (combined role-physical and role-emotional), social functioning, bodily pain, mental health, and vitality. SF-6D Health Utility Index (HUI) Score = 0 (worst measured health state) to 1 (best measured health state).
    End point type
    Secondary
    End point timeframe
    Baseline (Week 1), Weeks 26, 52, 78, 104 and 130
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: score on scale
    arithmetic mean (standard deviation)
        Baseline (n=98)
    0.70 ± 0.11
        Week 26 (n=92)
    -0.01 ± 0.12
        Week 52 (n=86)
    -0.01 ± 0.10
        Week 78 (n=87)
    -0.01 ± 0.12
        Week 104 (n=76)
    0.00 ± 0.11
        Week 130 (n=54)
    0.01 ± 0.13
    No statistical analyses for this end point

    Secondary: SMA Independence Scale (SMAIS) Score: Patient and Caregiver

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    End point title
    		 SMA Independence Scale (SMAIS) Score: Patient and Caregiver
    End point description
    The SMAIS was developed specifically for SMA in order to assess function-related independence. The SMAIS contains 29 items, assessing the amount of assistance required from another individual to perform daily activities, such as eating or transferring to/from a wheelchair. Each item is scored on a zero to four scale (with an additional option to indicate that an item is non-applicable). Item scores are summed to create the total score. Lower scores indicate greater dependence on another individual.
    End point type
    Secondary
    End point timeframe
    Week 104 and Week 130
    End point values
    		 Olesoxime
    Number of subjects analysed
    128
    Units: score on scale
    arithmetic mean (standard deviation)
        Patient, Week 104 (n=14)
    71.7 ± 23.4
        Patient, Week 130 (n=12)
    74.8 ± 22.5
        Caregiver, Week 104 (n=20)
    60.1 ± 22.2
        Caregiver, Week 130 (n=17)
    58.0 ± 24.9
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to approximately 3 years
    Adverse event reporting additional description
    Safety population included all patients who received at least one dose of study medication.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    Olesoxime
    Reporting group description
    		 Participants received a dose of 10 mg/kg suspension once a day (QD) orally or via a naso-gastric or gastronomy tube. Participants who consented to dose increase received 10 milligrams per kilogram (mg/kg) suspension twice a day (BID) either orally or via a naso-gastric or gastrostomy tube.

    Serious adverse events
    		 Olesoxime
    Total subjects affected by serious adverse events
         subjects affected / exposed
    36 / 131 (27.48%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    ACCIDENTAL OVERDOSE
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    FALL
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    FEMORAL NECK FRACTURE
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    FEMUR FRACTURE
         subjects affected / exposed
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    HUMERUS FRACTURE
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    JOINT DISLOCATION
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    POSTOPERATIVE WOUND COMPLICATION
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PROCEDURAL HAEMORRHAGE
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PROCEDURAL PAIN
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PROCEDURAL PNEUMOTHORAX
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    THERMAL BURN
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Surgical and medical procedures
    MEDICAL DEVICE REMOVAL
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    SKIN GRAFT
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    CONSTIPATION
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    VOMITING
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    GASTRITIS
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Reproductive system and breast disorders
    TESTICULAR TORSION
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    DYSPNOEA
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    LUNG DISORDER
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    OBSTRUCTIVE AIRWAYS DISORDER
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    RESPIRATORY DISTRESS
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    RESPIRATORY FAILURE
         subjects affected / exposed
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    ANXIETY
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    DEPRESSED MOOD
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    NEPHROLITHIASIS
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PATHOLOGICAL FRACTURE
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    BRONCHITIS
         subjects affected / exposed
    3 / 131 (2.29%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    GASTROENTERITIS
         subjects affected / exposed
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    ENCEPHALITIS
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    GASTROINTESTINAL INFECTION
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    4 / 131 (3.05%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    LUNG INFECTION
         subjects affected / exposed
    2 / 131 (1.53%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    OSTEOMYELITIS
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    10 / 131 (7.63%)
         occurrences causally related to treatment / all
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    PNEUMONIA VIRAL
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    POSTOPERATIVE WOUND INFECTION
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    VIRAL UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    FOOD REFUSAL
         subjects affected / exposed
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Olesoxime
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    105 / 131 (80.15%)
    Nervous system disorders
    HEADACHE
         subjects affected / exposed
    23 / 131 (17.56%)
         occurrences all number
    44
    General disorders and administration site conditions
    PYREXIA
         subjects affected / exposed
    28 / 131 (21.37%)
         occurrences all number
    40
    Gastrointestinal disorders
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    8 / 131 (6.11%)
         occurrences all number
    12
    CONSTIPATION
         subjects affected / exposed
    9 / 131 (6.87%)
         occurrences all number
    13
    NAUSEA
         subjects affected / exposed
    9 / 131 (6.87%)
         occurrences all number
    13
    DIARRHOEA
         subjects affected / exposed
    20 / 131 (15.27%)
         occurrences all number
    34
    VOMITING
         subjects affected / exposed
    23 / 131 (17.56%)
         occurrences all number
    43
    Respiratory, thoracic and mediastinal disorders
    COUGH
         subjects affected / exposed
    17 / 131 (12.98%)
         occurrences all number
    23
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    16 / 131 (12.21%)
         occurrences all number
    29
    Skin and subcutaneous tissue disorders
    RASH
         subjects affected / exposed
    8 / 131 (6.11%)
         occurrences all number
    10
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    12 / 131 (9.16%)
         occurrences all number
    14
    BACK PAIN
         subjects affected / exposed
    9 / 131 (6.87%)
         occurrences all number
    16
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    8 / 131 (6.11%)
         occurrences all number
    8
    Infections and infestations
    BRONCHITIS
         subjects affected / exposed
    15 / 131 (11.45%)
         occurrences all number
    22
    GASTROENTERITIS
         subjects affected / exposed
    13 / 131 (9.92%)
         occurrences all number
    18
    INFLUENZA
         subjects affected / exposed
    13 / 131 (9.92%)
         occurrences all number
    14
    PHARYNGITIS
         subjects affected / exposed
    7 / 131 (5.34%)
         occurrences all number
    9
    NASOPHARYNGITIS
         subjects affected / exposed
    30 / 131 (22.90%)
         occurrences all number
    57
    RHINITIS
         subjects affected / exposed
    10 / 131 (7.63%)
         occurrences all number
    15
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    36 / 131 (27.48%)
         occurrences all number
    63

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Sep 2015
    Clarity regarding contraception use, as well as withdrawal in case of pregnancy have been included in the protocol.
    19 Aug 2016
    The Hammersmith Functional Motor Scale (HFMS) scale was removed to decrease patient and site burden, the use of anticoagulants as prohibited medications was removed to align with the Investigator’s Brochure and added new information regarding pharmacokinetic characteristics of the study drug.
    14 Nov 2017
    Olesoxime dose increased from 10 mg/kg once daily (QD) to 10 mg/kg twice daily (BID) and a newly developed scale assessing function-related independence has been introduced as a patient-reported outcome measure: the SMA Independence Scale (SMAIS).

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    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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