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    Clinical Trial Results:
    A randomized, sham-controlled, double-blind study to evaluate the efficacy and safety of intrathecal (IT) OAV101 in patients with later onset Type 2 spinal muscular atrophy (SMA) who are ≥2 to <18 years of age, treatment naive, sitting, and never ambulatory

    Summary
    EudraCT number
    		 2021-003474-31
    Trial protocol
    		 DK   GR  
    Global end of trial date
    29 Apr 2025

    Results information
    Results version number
    		 v2(current)
    This version publication date
    28 Jan 2026
    First version publication date
    12 Nov 2025
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    COAV101B12301
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05089656
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 EudraCT: 2021-003474-31
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    Novartis Campus, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-002168-PIP01-06
    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
    29 Apr 2025
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Apr 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to compare the efficacy of OAV101B vs. sham procedure as measured by the change from baseline in Hammersmith Functional Motor Scale- Expanded (HFMSE) total score up to Week 52. The primary question of interest was: What is the effect of OAV101B treatment versus the sham procedure on change from baseline in HFMSE total score after treatment in sitting but never ambulatory patients aged 2 to <18 years with Type 2 SMA, regardless of study discontinuation or receipt of prohibited concomitant medications not for the intent to treat SMA?
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Feb 2022
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Brazil: 3
    Country: Number of subjects enrolled
    China: 27
    Country: Number of subjects enrolled
    Denmark: 3
    Country: Number of subjects enrolled
    India: 23
    Country: Number of subjects enrolled
    Malaysia: 6
    Country: Number of subjects enrolled
    Mexico: 14
    Country: Number of subjects enrolled
    Saudi Arabia: 1
    Country: Number of subjects enrolled
    Singapore: 5
    Country: Number of subjects enrolled
    South Africa: 10
    Country: Number of subjects enrolled
    Taiwan: 1
    Country: Number of subjects enrolled
    Thailand: 9
    Country: Number of subjects enrolled
    United States: 2
    Country: Number of subjects enrolled
    Viet Nam: 22
    Worldwide total number of subjects
    126
    EEA total number of subjects
    3
    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)
    117
    Adolescents (12-17 years)
    9
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 121 total participants were treated with a single dose of OAV101B (either in Period 1 (even if they did not complete Period 1) or Period 2).

    Period 1
    Period 1 title
    Period 1 - First Intervention (52 weeks)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 OAV101 first, then sham control
    Arm description
    		 OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2
    Arm type
    		 Experimental

    Investigational medicinal product name
    OAV101B
    Investigational medicinal product code
    OAV101B
    Other name
    onasemnogene abeparvovec
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intrathecal use
    Dosage and administration details
    OAV101B administered one time at a dose of 1.2 x 10^14 vg intrathecally in Period 1. (For eligible participants, a sham control needle prick was administered in Period 2)

    Arm title
    		 Sham control first, then OAV101
    Arm description
    		 A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg) in Period 2
    Arm type
    		 A skin prick without any medication.

    Investigational medicinal product name
    OAV101B
    Investigational medicinal product code
    OAV101B
    Other name
    onasemnogene abeparvovec
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intrathecal use
    Dosage and administration details
    For eligible participants OAV101B administered one time at a dose of 1.2 x 10^14 vg intrathecally in Period 2. (Sham control needle prick was administered in Period 1)

    Number of subjects in period 1
    		OAV101 first, then sham control Sham control first, then OAV101
    Started
    75
    51
    Completed period 1
    73
    50
    Completed
    67
    46
    Not completed
    8
    5
         Physician decision
    1
    -
         Protocol-specified withdrawal criterion met
    6
    4
         Adverse event, non-fatal
    -
    1
         Guardian decision
    1
    -
    Period 2
    Period 2 title
    Period 2 - 2nd Intervention (12 weeks)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 OAV101 first, then sham control
    Arm description
    		 OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2
    Arm type
    		 Experimental

    Investigational medicinal product name
    OAV101B
    Investigational medicinal product code
    OAV101B
    Other name
    onasemnogene abeparvovec
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intrathecal use
    Dosage and administration details
    OAV101B administered one time at a dose of 1.2 x 10^14 vg intrathecally in Period 1. (For eligible participants, a sham control needle prick was administered in Period 2)

    Arm title
    		 Sham control first, then OAV101
    Arm description
    		 A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg) in Period 2
    Arm type
    		 A skin prick without any medication.

    Investigational medicinal product name
    OAV101B
    Investigational medicinal product code
    OAV101B
    Other name
    onasemnogene abeparvovec
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intrathecal use
    Dosage and administration details
    For eligible participants OAV101B administered one time at a dose of 1.2 x 10^14 vg intrathecally in Period 2. (Sham control needle prick was administered in Period 1)

    Number of subjects in period 2
    		OAV101 first, then sham control Sham control first, then OAV101
    Started
    67
    46
    Completed
    67
    46

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    OAV101 first, then sham control
    Reporting group description
    		 OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2

    Reporting group title
    Sham control first, then OAV101
    Reporting group description
    		 A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg) in Period 2

    Reporting group values
    		 OAV101 first, then sham control Sham control first, then OAV101 Total
    Number of subjects
    		 75 51 126
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 69 48 117
        Adolescents (12-17 years)
    		 6 3 9
        Adults (18-64 years)
    		 0 0 0
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 5.71 ( 3.575 ) 5.68 ( 3.045 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 41 23 64
        Male
    		 34 28 62
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 2 5 7
        Asian
    		 49 25 74
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 5 4 9
        White
    		 7 7 14
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 12 10 22
    Subject analysis sets

    Subject analysis set title
    Overall OAV101 in Periods 1 and 2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg). -For participants randomized to OAV101B in Period 1: All AEs from Period 1 and 2 -For participants randomized to the sham control in Period 1 and who were administered OAV101 in Period 2: All AEs from Period 2

    Subject analysis set title
    Overall OAV101 in Periods 1 and 2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg). -For participants randomized to OAV101B in Period 1: All intracardiac thrombi events from Period 1 and 2 -For participants randomized to the sham control in Period 1 and who were administered OAV101 in Period 2: All intracardiac thrombi events from Period 2

    Subject analysis set title
    Overall OAV101 in Periods 1 and 2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg). -For participants randomized to OAV101B in Period 1: All low cardiac function events from Period 1 and 2 -For participants randomized to the sham control in Period 1 and who were administered OAV101 in Period 2: All low cardiac function events from Period 2

    Subject analysis set title
    OAV101 Period 1
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg) in Period 1

    Subject analysis set title
    Sham control Period 1
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    A skin prick in the lumbar region without any medication in Period 1

    Subject analysis sets values
    		 Overall OAV101 in Periods 1 and 2 Overall OAV101 in Periods 1 and 2 Overall OAV101 in Periods 1 and 2 OAV101 Period 1 Sham control Period 1
    Number of subjects
    121
    121
    121
    75
    51
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    ( )
    1 ( )
    17 ( )
    ( )
    ( )
    Sex: Female, Male
    Units: Participants
        Female
        Male
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
        Asian
        Native Hawaiian or Other Pacific Islander
        Black or African American
        White
        More than one race
        Unknown or Not Reported

    End points

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    End points reporting groups
    Reporting group title
    OAV101 first, then sham control
    Reporting group description
    		 OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2

    Reporting group title
    Sham control first, then OAV101
    Reporting group description
    		 A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg) in Period 2
    Reporting group title
    OAV101 first, then sham control
    Reporting group description
    		 OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg) in Period 1, then a skin prick in the lumbar region without any medication in Period 2

    Reporting group title
    Sham control first, then OAV101
    Reporting group description
    		 A skin prick in the lumbar region without any medication in Period 1, then OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg) in Period 2

    Subject analysis set title
    Overall OAV101 in Periods 1 and 2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg). -For participants randomized to OAV101B in Period 1: All AEs from Period 1 and 2 -For participants randomized to the sham control in Period 1 and who were administered OAV101 in Period 2: All AEs from Period 2

    Subject analysis set title
    Overall OAV101 in Periods 1 and 2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg). -For participants randomized to OAV101B in Period 1: All intracardiac thrombi events from Period 1 and 2 -For participants randomized to the sham control in Period 1 and who were administered OAV101 in Period 2: All intracardiac thrombi events from Period 2

    Subject analysis set title
    Overall OAV101 in Periods 1 and 2
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg). -For participants randomized to OAV101B in Period 1: All low cardiac function events from Period 1 and 2 -For participants randomized to the sham control in Period 1 and who were administered OAV101 in Period 2: All low cardiac function events from Period 2

    Subject analysis set title
    OAV101 Period 1
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10^14 vector genomes (vg) in Period 1

    Subject analysis set title
    Sham control Period 1
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    A skin prick in the lumbar region without any medication in Period 1

    Primary: Change from baseline at the end of Period 1 in the Hammersmith Functional Motor Scale Expanded - total score - in the ≥ 2 to < 18 years age group

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    End point title
    		 Change from baseline at the end of Period 1 in the Hammersmith Functional Motor Scale Expanded - total score - in the ≥ 2 to < 18 years age group
    End point description
    The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.
    End point type
    Primary
    End point timeframe
    Baseline, Week 52 (or Week 48)
    End point values
    		 OAV101 first, then sham control Sham control first, then OAV101
    Number of subjects analysed
    74
    50
    Units: Scores on a scale
        least squares mean (standard error)
    2.39 ( 0.439 )
    0.51 ( 0.532 )
    Statistical analysis title
    		 OAV101 v Sham control
    Statistical analysis description
    Change from baseline at End of Follow-up Period 1
    Comparison groups
    OAV101 first, then sham control v Sham control first, then OAV101
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0074
    Method
    		 Mixed models analysis
    Parameter type
    		 LS-Means difference
    Point estimate
    1.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 3.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.69

    Secondary: Change from baseline in HFMSE total score at the end of Follow-up Period 1 in treated patients compared to sham controls in the ≥ 2 to < 5 years age group

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    End point title
    		 Change from baseline in HFMSE total score at the end of Follow-up Period 1 in treated patients compared to sham controls in the ≥ 2 to < 5 years age group
    End point description
    The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52 (or Week 48)
    End point values
    		 OAV101 first, then sham control Sham control first, then OAV101
    Number of subjects analysed
    41
    29
    Units: Scores on a scale
        least squares mean (standard error)
    3.00 ( 0.569 )
    1.56 ( 0.683 )
    Statistical analysis title
    		 OAV101 v Sham control
    Statistical analysis description
    Change from baseline at End of Follow-up Period 1
    Comparison groups
    OAV101 first, then sham control v Sham control first, then OAV101
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1097
    Method
    		 Mixed models analysis
    Parameter type
    		 LS-Means - difference
    Point estimate
    1.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.33
         upper limit
    		 3.22
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.889

    Secondary: Change from baseline in Revised Upper Limb Module (RULM) total score at the end of Follow-up Period 1 in treated patients compared to sham controls in the ≥ 2 to < 18 years age group

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    End point title
    		 Change from baseline in Revised Upper Limb Module (RULM) total score at the end of Follow-up Period 1 in treated patients compared to sham controls in the ≥ 2 to < 18 years age group
    End point description
    The RULM is a validated SMA specific assessment of motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. The scale consists of 19 scorable items: 18 items scored on 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). Total scores range from 0-37 points. Higher scores reflect higher level of motor ability.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52 (or Week 48)
    End point values
    		 OAV101 first, then sham control Sham control first, then OAV101
    Number of subjects analysed
    74
    50
    Units: Scores on a scale
        least squares mean (standard error)
    2.44 ( 0.381 )
    0.92 ( 0.462 )
    Statistical analysis title
    		 OAV101 v Sham control
    Statistical analysis description
    Change from baseline at End of Follow-up Period 1
    Comparison groups
    OAV101 first, then sham control v Sham control first, then OAV101
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0122
    Method
    		 Mixed models analysis
    Parameter type
    		 LS-Means difference
    Point estimate
    1.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.34
         upper limit
    		 2.71
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.599

    Secondary: Change from baseline in the RULM total score at the end of Follow-up Period 1 in treated patients compared to sham controls in the ≥ 2 to < 5 years age group

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    End point title
    		 Change from baseline in the RULM total score at the end of Follow-up Period 1 in treated patients compared to sham controls in the ≥ 2 to < 5 years age group
    End point description
    The RULM is a validated SMA specific assessment of motor performance in the upper limbs from childhood through adulthood in ambulatory and non-ambulatory individuals with SMA. The scale consists of 19 scorable items: 18 items scored on a 0 (unable) to 2 (full achievement) scale, and one item that is scored from 0 (unable) to 1 (able). Total scores range from 0-37 points. Higher scores reflect higher level of motor ability.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52 (or Week 48)
    End point values
    		 OAV101 first, then sham control Sham control first, then OAV101
    Number of subjects analysed
    41
    29
    Units: Scores on a scale
        least squares mean (standard error)
    3.27 ( 0.535 )
    1.82 ( 0.642 )
    Statistical analysis title
    		 OAV101 v Sham control
    Statistical analysis description
    Change from baseline at End of Follow-up Period 1
    Comparison groups
    OAV101 first, then sham control v Sham control first, then OAV101
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0873
    Method
    		 Mixed models analysis
    Parameter type
    		 LS-Means difference
    Point estimate
    1.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.22
         upper limit
    		 3.12
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.836

    Secondary: % of participants who achieved at least a 3-point improvement from baseline in HFMSE total score at the end of Follow-up Period 1 in the ≥ 2 to < 18 years age group

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    End point title
    		 % of participants who achieved at least a 3-point improvement from baseline in HFMSE total score at the end of Follow-up Period 1 in the ≥ 2 to < 18 years age group
    End point description
    The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52 (or Week 48) (end of Period 1)
    End point values
    		 OAV101 first, then sham control Sham control first, then OAV101
    Number of subjects analysed
    74
    50
    Units: % of participants
        number (confidence interval 95%)
    39.2 (28.07 to 50.31)
    26.0 (13.84 to 38.16)
    Statistical analysis title
    		 OAV101 v Sham control
    Statistical analysis description
    End of Followup Period 1 (Week 52)
    Comparison groups
    OAV101 first, then sham control v Sham control first, then OAV101
    Number of subjects included in analysis
    124
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0879
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 4.57

    Secondary: % of participants who achieved at least a 3-point improvement from baseline in HFMSE total score at the end of Follow-up Period 1 for participants aged ≥ 2 to < 5 years

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    End point title
    		 % of participants who achieved at least a 3-point improvement from baseline in HFMSE total score at the end of Follow-up Period 1 for participants aged ≥ 2 to < 5 years
    End point description
    The HFMSE is a validated SMA specific assessment devised for use in children with SMA to give objective information on motor ability and clinical progression. The HFMSE contains 33 items rated from 0 (unable to perform) to 2 (performs without modification/adaptation/compensation). Total scores range from 0-66. Higher scores indicate higher levels of motor ability.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52 (or Week 48)(end of Period 1)
    End point values
    		 OAV101 first, then sham control Sham control first, then OAV101
    Number of subjects analysed
    41
    29
    Units: % of participants
        number (confidence interval 95%)
    48.8 (33.48 to 64.08)
    37.9 (20.27 to 55.59)
    Statistical analysis title
    		 OAV101 v Sham control
    Statistical analysis description
    End of Followup Period 1 (Week 52)
    Comparison groups
    OAV101 first, then sham control v Sham control first, then OAV101
    Number of subjects included in analysis
    70
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.6448
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.46
         upper limit
    		 3.56

    Secondary: Number of participants with treatment emergent Adverse Events and Serious Adverse Events

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    End point title
    		 Number of participants with treatment emergent Adverse Events and Serious Adverse Events
    End point description
    An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. A Treatment Emergent Adverse Event (TEAE) is defined as an event that emerges during treatment, having been absent pretreatment, or worsens relative to the pretreatment state. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments. pt = participant pts = participants
    End point type
    Secondary
    End point timeframe
    Adverse events are reported from the start of treatment period 1 plus 64 weeks, up to a maximum time period of 64 weeks.
    End point values
    		 Overall OAV101 in Periods 1 and 2 OAV101 Period 1 Sham control Period 1
    Number of subjects analysed
    121
    75
    51
    Units: Participants
        Any treatment-emergent adverse event (TEAE)
    104
    74
    46
        Any TEAE related to study treatment
    36
    27
    5
        Any serious treatment-emergent adverse event
    34
    21
    17
        Any serious TEAE related to study treatment
    12
    8
    1
        Any severe treatment-emergent adverse event
    12
    8
    9
        Any TEAE leading to study disc.
    0
    0
    1
        Any TEAE leading to death
    0
    0
    0
        Any TEAE of special interest
    21
    12
    7
    No statistical analyses for this end point

    Secondary: Number of participants with adverse events of special interest (AESI)

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    End point title
    		 Number of participants with adverse events of special interest (AESI)
    End point description
    An AESI is primarily defined by using standard Medical Dictionary for Regulatory Activities (MedDRA) queries, and identified as follows: - Hepatotoxicity - Thrombocytopenia - Cardiac adverse events - Signs and symptoms that may be suggestive of dorsal root ganglia toxicity - Thrombotic microangiopathy - New malignancies Adverse events for Periods 1 and 2 are combined in the overall OAV101 arm because the same active treatment (and same single dose) was administered in either Period1 or Period 2. Because this is a gene therapy, which permanently impacts the genetics of the study participant, participants randomized to OAV101 in Period 1 are still considered on treatment with OAV101 in Period 2 (after receiving sham control in Period 2). Therefore, adverse events for the Sham arm can only be considered from Period 1.
    End point type
    Secondary
    End point timeframe
    Adverse events are reported from the start of treatment period 1 plus 64 weeks, up to a maximum time period of 64 weeks.
    End point values
    		 Overall OAV101 in Periods 1 and 2 OAV101 Period 1 Sham control Period 1
    Number of subjects analysed
    121
    75
    51
    Units: Participants
        Hepatotoxicity
    10
    7
    5
        Transient thrombocytopenia
    9
    4
    2
        Cardiac adverse events
    0
    0
    0
        Signs and symptoms of dorsal root ganglia toxicity
    3
    2
    1
        Thrombotic microangiopathy
    0
    0
    0
        New malignancies
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number (and percentage) of patients with intracardiac thrombi

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    End point title
    		 Number (and percentage) of patients with intracardiac thrombi
    End point description
    Intracardiac thrombi is defined as the presence of thrombus on post-baseline echocardiograms. Events for Periods 1 and 2 are combined in the overall OAV101 arm because the same active treatment (and same single dose) was administered in either Period1 or Period 2. Because this is a gene therapy, which permanently impacts the genetics of the study participant, participants randomized to OAV101 in Period 1 are still considered on treatment with OAV101 in Period 2 (after receiving sham control in Period 2). Therefore, events for the Sham arm can only be considered from Period 1.
    End point type
    Secondary
    End point timeframe
    Baseline up to 64 weeks
    End point values
    		 Overall OAV101 in Periods 1 and 2 OAV101 Period 1 Sham control Period 1
    Number of subjects analysed
    121
    75
    51
    Units: Participants
    1
    0
    1
    No statistical analyses for this end point

    Secondary: Number(and percentage) of patients with low cardiac function

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    End point title
    		 Number(and percentage) of patients with low cardiac function
    End point description
    Low cardiac function is defined as left ventricular ejection fraction <56% or left ventricular fractional shortening <28% on post-baseline echocardigrams. Events for Periods 1 and 2 are combined in the overall OAV101 arm because the same active treatment (and same single dose) was administered in either Period1 or Period 2. Because this is a gene therapy, which permanently impacts the genetics of the study participant, participants randomized to OAV101 in Period 1 are still considered on treatment with OAV101 in Period 2 (after receiving sham control in Period 2). Therefore, events for the Sham arm can only be considered from Period 1.
    End point type
    Secondary
    End point timeframe
    Baseline up to 64 weeks
    End point values
    		 Overall OAV101 in Periods 1 and 2 OAV101 Period 1 Sham control Period 1
    Number of subjects analysed
    121
    75
    51
    Units: Participants
    17
    8
    9
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events (AEs) are reported from the start of treatment period 1 plus 64 weeks, up to a maximum time period of 64 weeks.
    Adverse event reporting additional description
    AEs for Periods 1 and 2 are combined in the overall OAV101 arm because the same active treatment (and same single dose) was administered in either Period1 or Period 2.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    28.0
    Reporting groups
    Reporting group title
    Period 1: OAV101B
    Reporting group description
    		 Period 1: OAV101B

    Reporting group title
    Overall: OAV101B@Period 1 + Period 2
    Reporting group description
    		 Overall: OAV101B@Period 1 + Period 2

    Reporting group title
    Period 1: Sham
    Reporting group description
    		 Period 1: Sham

    Serious adverse events
    		 Period 1: OAV101B Overall: OAV101B@Period 1 + Period 2 Period 1: Sham
    Total subjects affected by serious adverse events
         subjects affected / exposed
    21 / 75 (28.00%)
    34 / 121 (28.10%)
    17 / 51 (33.33%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Cardiac disorders
    Arrhythmia
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Peripheral sensory neuropathy
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoaesthesia
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 75 (1.33%)
    3 / 121 (2.48%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    3 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 121 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    3 / 75 (4.00%)
    5 / 121 (4.13%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    2 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Atelectasis
         subjects affected / exposed
    1 / 75 (1.33%)
    2 / 121 (1.65%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wheezing
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 121 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal discomfort
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Coronavirus pneumonia
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis viral
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 121 (0.83%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 121 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    9 / 75 (12.00%)
    16 / 121 (13.22%)
    7 / 51 (13.73%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 19
    0 / 12
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mycoplasma infection
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metapneumovirus infection
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 75 (2.67%)
    2 / 121 (1.65%)
    4 / 51 (7.84%)
         occurrences causally related to treatment / all
    2 / 8
    2 / 9
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    2 / 75 (2.67%)
    2 / 121 (1.65%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infective exacerbation of bronchiectasis
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 121 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hand-foot-and-mouth disease
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 121 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 121 (0.83%)
    2 / 51 (3.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia mycoplasmal
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 121 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    2 / 51 (3.92%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 75 (1.33%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 121 (0.83%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 121 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Period 1: OAV101B Overall: OAV101B@Period 1 + Period 2 Period 1: Sham
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    63 / 75 (84.00%)
    85 / 121 (70.25%)
    43 / 51 (84.31%)
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    4 / 75 (5.33%)
    5 / 121 (4.13%)
    1 / 51 (1.96%)
         occurrences all number
    6
    9
    1
    Headache
         subjects affected / exposed
    7 / 75 (9.33%)
    10 / 121 (8.26%)
    2 / 51 (3.92%)
         occurrences all number
    10
    14
    2
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    19 / 75 (25.33%)
    23 / 121 (19.01%)
    12 / 51 (23.53%)
         occurrences all number
    25
    32
    17
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 75 (1.33%)
    2 / 121 (1.65%)
    8 / 51 (15.69%)
         occurrences all number
    2
    3
    10
    Constipation
         subjects affected / exposed
    11 / 75 (14.67%)
    15 / 121 (12.40%)
    11 / 51 (21.57%)
         occurrences all number
    12
    18
    14
    Nausea
         subjects affected / exposed
    4 / 75 (5.33%)
    6 / 121 (4.96%)
    3 / 51 (5.88%)
         occurrences all number
    5
    7
    3
    Vomiting
         subjects affected / exposed
    13 / 75 (17.33%)
    18 / 121 (14.88%)
    6 / 51 (11.76%)
         occurrences all number
    17
    25
    8
    Respiratory, thoracic and mediastinal disorders
    Respiratory tract inflammation
         subjects affected / exposed
    2 / 75 (2.67%)
    2 / 121 (1.65%)
    3 / 51 (5.88%)
         occurrences all number
    2
    2
    3
    Oropharyngeal pain
         subjects affected / exposed
    5 / 75 (6.67%)
    8 / 121 (6.61%)
    0 / 51 (0.00%)
         occurrences all number
    6
    12
    0
    Cough
         subjects affected / exposed
    11 / 75 (14.67%)
    15 / 121 (12.40%)
    11 / 51 (21.57%)
         occurrences all number
    20
    27
    13
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    2 / 75 (2.67%)
    5 / 121 (4.13%)
    3 / 51 (5.88%)
         occurrences all number
    2
    5
    3
    Urticaria
         subjects affected / exposed
    2 / 75 (2.67%)
    3 / 121 (2.48%)
    4 / 51 (7.84%)
         occurrences all number
    2
    3
    4
    Musculoskeletal and connective tissue disorders
    Osteoporosis
         subjects affected / exposed
    0 / 75 (0.00%)
    0 / 121 (0.00%)
    3 / 51 (5.88%)
         occurrences all number
    0
    0
    3
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    4 / 75 (5.33%)
    7 / 121 (5.79%)
    3 / 51 (5.88%)
         occurrences all number
    4
    8
    3
    Influenza
         subjects affected / exposed
    4 / 75 (5.33%)
    5 / 121 (4.13%)
    5 / 51 (9.80%)
         occurrences all number
    4
    5
    5
    Lower respiratory tract infection
         subjects affected / exposed
    6 / 75 (8.00%)
    7 / 121 (5.79%)
    4 / 51 (7.84%)
         occurrences all number
    12
    15
    11
    Pharyngitis
         subjects affected / exposed
    3 / 75 (4.00%)
    5 / 121 (4.13%)
    4 / 51 (7.84%)
         occurrences all number
    3
    5
    5
    Nasopharyngitis
         subjects affected / exposed
    8 / 75 (10.67%)
    11 / 121 (9.09%)
    5 / 51 (9.80%)
         occurrences all number
    11
    16
    7
    Pneumonia
         subjects affected / exposed
    0 / 75 (0.00%)
    1 / 121 (0.83%)
    3 / 51 (5.88%)
         occurrences all number
    0
    1
    3
    Upper respiratory tract infection
         subjects affected / exposed
    26 / 75 (34.67%)
    34 / 121 (28.10%)
    15 / 51 (29.41%)
         occurrences all number
    43
    57
    22
    Respiratory tract infection
         subjects affected / exposed
    3 / 75 (4.00%)
    5 / 121 (4.13%)
    3 / 51 (5.88%)
         occurrences all number
    3
    6
    5

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Mar 2022
    The data analysis and statistical methods section were revised to include the following two secondary endpoints: • Achievement of at least a 3-point improvement from baseline in HFMSE total score at the end of Follow-up Period 1 in the overall study population • Achievement of at least a 3-point improvement from baseline in HFMSE total score at the end of Follow-up Period 1 in the 2 to <5 years age group. The schedule of sensory nerve action potential (SNAP) assessments were modified.
    08 Aug 2022
    The Central Treatment Site (hybrid model) was removed, adaptations were made to inclusion/exclusion criteria, updates were made on OAV101 risks, and the visit schedule for troponin I collection was modified.
    02 Jun 2023
    Several exclusion criteria were revised to be anchored to the Day 1 visit (day of OAV101 administration or the sham procedure) and a theoretical risk of tumorigenicity due to vector DNA integration has been added to the OAV101 risks section.
    17 May 2024
    Updated to enhance consultation between the Principal Investigator and Sponsors for retesting of abnormal laboratory parameters and to ensure compliance with expedited reporting of potential Hy’s Law cases based on health authority guidance.

    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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