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    Clinical Trial Results:
    A subject-, investigator-, and sponsor-blinded, randomized, placebo-controlled, multicenter study to investigate efficacy, safety, and tolerability of VAY736 in patients with idiopathic pulmonary fibrosis

    Summary
    EudraCT number
    		 2017-002667-17
    Trial protocol
    		 GB   IE   DE   IT   FR  
    Global end of trial date
    14 Feb 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 Mar 2023
    First version publication date
    02 Mar 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CVAY736X2207
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03287414
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, 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)
    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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 Feb 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Feb 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To assess the efficacy of VAY736 in patients with IPF by looking at the change from baseline to end-of-treatment (48 weeks of treatment) in forced vital capacity (FVC).
    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
    20 Dec 2017
    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
    Canada: 1
    Country: Number of subjects enrolled
    Germany: 8
    Country: Number of subjects enrolled
    Ireland: 5
    Country: Number of subjects enrolled
    Italy: 4
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    United States: 10
    Worldwide total number of subjects
    30
    EEA total number of subjects
    17
    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)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    8
    From 65 to 84 years
    22
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study was conducted across 16 centers in 6 countries.

    Pre-assignment
    Screening details
    		 A total of 142 participants were screened of which 30 participants were randomized. 1 participant in the VAY736 arm did not receive treatment as the patient withdrew consent before first dosing.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 VAY736
    Arm description
    		 Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ianalumab
    Investigational medicinal product code
    VAY736sub
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks

    Arm title
    		 Placebo
    Arm description
    		 Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo administered subcutaneously every 4 weeks for 48 weeks

    Number of subjects in period 1 [1]
    		VAY736 Placebo
    Started
    13
    16
    Completed
    6
    12
    Not completed
    7
    4
         Study terminated by Sponsor
    2
    2
         Discontinued early with reason "other" selected
    1
    1
         Adverse event, non-fatal
    -
    1
         Subject/Guardian decision
    4
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: 1 participant randomized was never treated

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    VAY736
    Reporting group description
    		 Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy

    Reporting group values
    		 VAY736 Placebo Total
    Number of subjects
    		 13 16 29
    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)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 3 5 8
        From 65-84 years
    		 10 11 21
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 69.7 ± 9.30 68.3 ± 8.15 -
    Gender categorical
    Units: Subjects
        Female
    		 1 1 2
        Male
    		 12 15 27
    Race/Ethnicity
    Units: Subjects
        White
    		 13 16 29

    End points

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    End points reporting groups
    Reporting group title
    VAY736
    Reporting group description
    		 Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy

    Primary: Change from baseline to end of treatment epoch (48 weeks of treatment) in Forced Vital Capacity (FVC)

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    End point title
    		 Change from baseline to end of treatment epoch (48 weeks of treatment) in Forced Vital Capacity (FVC)
    End point description
    FVC was defined as the maximum amount of air that an individual was able to forcibly exhale from his / her lungs after taking the deepest breath they could. Change from baseline to end of treatment epoch (48 weeks of treatment) in Forced Vital Capacity (FVC) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.
    End point type
    Primary
    End point timeframe
    From baseline up to 48 weeks post first dose of study treatment
    End point values
    		 VAY736 Placebo
    Number of subjects analysed
    3
    16
    Units: Liter (L)
        least squares mean (standard error)
    0.039 ± 0.1116
    -0.023 ± 0.0773
    Statistical analysis title
    		 Change from baseline in FVC
    Comparison groups
    VAY736 v Placebo
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3248 [1]
    Method
    		 MMRM
    Parameter type
    		 Least Squares Mean Difference
    Point estimate
    0.063
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -0.115
         upper limit
    		 0.241
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.1379
    Notes
    [1] - 1-sided p-values were obtained using MMRM Model.

    Secondary: Percentage of participants with all-cause mortality events

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    End point title
    		 Percentage of participants with all-cause mortality events
    End point description
    All-cause mortality events were defined as deaths due to any cause. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood’s formula are provided.
    End point type
    Secondary
    End point timeframe
    Up to 48 weeks post first dose of study treatment
    End point values
    		 VAY736 Placebo
    Number of subjects analysed
    12
    16
    Units: Percentage of participants
        number (confidence interval 80%)
    8.3 (2.39 to 26.92)
    0 (-9999 to 9999)
    Statistical analysis title
    		 Survival Analysis: All-cause mortality
    Comparison groups
    VAY736 v Placebo
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.868
    Method
    		 Logrank
    Confidence interval

    Secondary: Percentage of participants with survival Idiopathic Pulmonary Fibrosis (IPF) -related mortality events

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    End point title
    		 Percentage of participants with survival Idiopathic Pulmonary Fibrosis (IPF) -related mortality events
    End point description
    IPF-related mortality events were defined as deaths due to IPF related cause. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood’s formula are provided.
    End point type
    Secondary
    End point timeframe
    Up to 48 weeks post first dose of study treatment
    End point values
    		 VAY736 Placebo
    Number of subjects analysed
    12
    16
    Units: Percentage of participants
        number (confidence interval 80%)
    0 (-9999 to 9999)
    0 (-9999 to 9999)
    No statistical analyses for this end point

    Secondary: Percentage of participants with Progression-free survival (PFS) events

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    End point title
    		 Percentage of participants with Progression-free survival (PFS) events
    End point description
    PFS events were divided into: 1) PFS1 events including progression (relative reduction in FVC ≥ 10%) or death due to all causes, and 2) PFS2 events including progression (relative reduction in FVC ≥ 10%) or death due to IPF-related causes. Kaplan-Meier estimates of the percentage of participants with the event of interest (PFS1 events or PFS2 events) along with 80% two-sided confidence intervals using Greenwood’s formula are provided.
    End point type
    Secondary
    End point timeframe
    Up to 48 weeks post first dose of study treatment
    End point values
    		 VAY736 Placebo
    Number of subjects analysed
    12
    16
    Units: Percentage of participants
    number (confidence interval 80%)
        PFS1
    61.0 (38.22 to 84.20)
    31.9 (18.04 to 52.51)
        PFS2
    57.1 (33.44 to 82.86)
    31.9 (18.04 to 52.51)
    Statistical analysis title
    		 Survival analysis: PFS1
    Comparison groups
    VAY736 v Placebo
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.921
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    2.6
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 1.1
         upper limit
    		 6.3
    Statistical analysis title
    		 Survival analysis: PFS2
    Comparison groups
    VAY736 v Placebo
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.863
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    2.2
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 5.6

    Secondary: Percentage of participants with disease progression events

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    End point title
    		 Percentage of participants with disease progression events
    End point description
    The following disease progression events were considered: a) relative reduction in FVC ≥ 10%; b) relative reduction in Diffusing Capacity of the Lungs (DLCO) ≥ 15%; c) absolute reduction in Six Minute Walk Distance (6MWD) ≥ 50 m. Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood’s formula are provided.
    End point type
    Secondary
    End point timeframe
    Up to 48 weeks post first dose of study treatment
    End point values
    		 VAY736 Placebo
    Number of subjects analysed
    12
    16
    Units: Percentage of participants
    number (confidence interval 80%)
        FVC
    57.1 (33.44 to 82.86)
    31.9 (18.08 to 52.51)
        DLCO
    73.8 (46.56 to 92.24)
    56.1 (36.65 to 75.10)
        6MWD
    38.3 (19.96 to 64.88)
    75.0 (58.52 to 88.74)
    Statistical analysis title
    		 Survival Analysis: FVC
    Comparison groups
    Placebo v VAY736
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.863
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    2.2
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.9
         upper limit
    		 5.6
    Statistical analysis title
    		 Survival Analysis: DLCO
    Comparison groups
    VAY736 v Placebo
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.457
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.9
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 2
    Statistical analysis title
    		 Survival Analysis: 6MWD
    Comparison groups
    VAY736 v Placebo
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.019
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.3
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.1
         upper limit
    		 0.6

    Secondary: Percentage of participants with composite events

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    End point title
    		 Percentage of participants with composite events
    End point description
    Composite events were defined as: 1) death (all-cause mortality), or relative reduction in FVC ≥ 10%, or relative reduction in DLCO ≥ 15%, or relative reduction in 6MWD ≥ 50 m (composite endpoint 1); and 2) Death (IPF-related mortality), or relative reduction in FVC ≥ 10%, or relative reduction in DLCO ≥ 15%, or relative reduction in 6MWD ≥ 50 m (composite endpoint 2). Kaplan-Meier estimates of the percentage of participants with the event of interest along with 80% two-sided confidence intervals using Greenwood’s formula are provided
    End point type
    Secondary
    End point timeframe
    Up to 48 weeks post first dose of study treatment
    End point values
    		 VAY736 Placebo
    Number of subjects analysed
    12
    16
    Units: Percentage of participants
    number (confidence interval 80%)
        Composite Endpoint 1
    81.0 (63.86 to 93.29)
    66.3 (50.84 to 81.18)
        Composite Endpoint 2
    79.2 (61.07 to 92.70)
    66.3 (50.84 to 81.18)
    Statistical analysis title
    		 Survival Analysis: Composite Endpoint 1
    Comparison groups
    VAY736 v Placebo
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.611
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.1
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 2
    Statistical analysis title
    		 Survival Analysis: Composite Endpoint 2
    Comparison groups
    VAY736 v Placebo
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.549
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.1
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 1.9

    Secondary: Change from baseline to end of treatment epoch (48 weeks of treatment) in Diffusing Capacity of the Lungs

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    End point title
    		 Change from baseline to end of treatment epoch (48 weeks of treatment) in Diffusing Capacity of the Lungs
    End point description
    DLCO is a measurement to assess the lungs' ability to transfer gas from inspired air to the bloodstream. DLCO was determined according to ATS guidelines. Change from baseline to end of treatment epoch (48 weeks of treatment) in diffusing capacity of the lung for carbon monoxide (DLCO) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.
    End point type
    Secondary
    End point timeframe
    From baseline up to 48 weeks post first dose of study treatment
    End point values
    		 VAY736 Placebo
    Number of subjects analysed
    3
    7
    Units: mililiter/minute/millimeter Mercury
        least squares mean (standard error)
    -1.954 ± 1.0816
    -1.033 ± 0.7244
    Statistical analysis title
    		 Change from baseline in DLCO
    Comparison groups
    VAY736 v Placebo
    Number of subjects included in analysis
    10
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.7576 [2]
    Method
    		 MMRM
    Parameter type
    		 Least Squares of the Mean
    Point estimate
    -0.92
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -2.615
         upper limit
    		 0.774
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.3109
    Notes
    [2] - 1-sided p-values were obtained using MMRM Model.

    Secondary: Change from baseline to the end of treatment epoch (48 weeks of treatment) in 6-minute walk distance (6MWD)

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    End point title
    		 Change from baseline to the end of treatment epoch (48 weeks of treatment) in 6-minute walk distance (6MWD)
    End point description
    A standardized 6-minute walk test (6MWT) was performed in accordance with the guidelines of the American Thoracic Society 2002. The distance walked in six minutes (6MWD) was recorded. Change from baseline to end of treatment epoch (48 weeks of treatment) in 6MWD was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.
    End point type
    Secondary
    End point timeframe
    From baseline up to 48 weeks post first dose of study treatment
    End point values
    		 VAY736 Placebo
    Number of subjects analysed
    2
    7
    Units: Meter (m)
        least squares mean (standard error)
    19.743 ± 19.743
    -12.479 ± 28.9400
    Statistical analysis title
    		 Change from baseline in 6MWD
    Comparison groups
    VAY736 v Placebo
    Number of subjects included in analysis
    9
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3018 [3]
    Method
    		 MMRM
    Parameter type
    		 Least Squares of the Mean
    Point estimate
    32.222
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -47.572
         upper limit
    		 112.015
    Variability estimate
    Standard error of the mean
    Dispersion value
    61.8632
    Notes
    [3] - Change from baseline in 6MWD

    Secondary: Change from baseline to the end of treatment epoch (48 weeks of treatment) in distance saturation product

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    End point title
    		 Change from baseline to the end of treatment epoch (48 weeks of treatment) in distance saturation product
    End point description
    Distance saturation product is the product of distance walked and lowest oxygen saturation during the 6-min walk test. Change from baseline to end of treatment epoch (48 weeks of treatment) in distance saturation product was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.
    End point type
    Secondary
    End point timeframe
    From baseline up to 48 weeks post first dose of study treatment
    End point values
    		 VAY736 Placebo
    Number of subjects analysed
    2
    7
    Units: Meter% (m%)
        least squares mean (standard error)
    9.746 ± 52.2985
    -19.420 ± 28.3755
    Statistical analysis title
    		 Distance saturation product
    Comparison groups
    VAY736 v Placebo
    Number of subjects included in analysis
    9
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.314 [4]
    Method
    		 MMRM
    Parameter type
    		 Least Squares of the Mean
    Point estimate
    29.166
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -48.22
         upper limit
    		 106.553
    Variability estimate
    Standard error of the mean
    Dispersion value
    60.0143
    Notes
    [4] - 1-sided p-values were obtained using MMRM Model.

    Secondary: Change from baseline to the end of treatment epoch (48 weeks of treatment) in resting oxygen saturation level (on room air)

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    End point title
    		 Change from baseline to the end of treatment epoch (48 weeks of treatment) in resting oxygen saturation level (on room air)
    End point description
    Change from baseline to end of treatment epoch (48 weeks of treatment) in resting oxygen saturation (on room air) was analyzed using a Mixed Effects Model for Repeated Measures (MMRM) and considering all assessments collected during the treatment epoch. The model included treatment and visit as fixed effects, standard of care treatment (Nintedanib, Pirfenidone, or no treatment) as factor and baseline value as a covariate, treatment-by-visit and baseline-by-visit as interaction terms. A positive change from baseline indicates improvement. Baseline was defined as the last available assessment pre-dose before or on randomization date.
    End point type
    Secondary
    End point timeframe
    From baseline up to 48 weeks post first dose of study treatment
    End point values
    		 VAY736 Placebo
    Number of subjects analysed
    5
    7
    Units: Percentage (%)
        least squares mean (standard error)
    -0.117 ± 1.0179
    -1.887 ± 0.9415
    Statistical analysis title
    		 Resting oxygen saturation level
    Comparison groups
    Placebo v VAY736
    Number of subjects included in analysis
    12
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1269 [5]
    Method
    		 MMRM
    Parameter type
    		 Least Squares of the mean
    Point estimate
    1.77
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -0.219
         upper limit
    		 3.759
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.5422
    Notes
    [5] - 1-sided p-values were obtained using MMRM Model.

    Secondary: Number of participants with positive serum anti-VAY736 antibodies

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    End point title
    		 Number of participants with positive serum anti-VAY736 antibodies
    End point description
    Number of participants with positive serum anti-VAY736 antibodies. A bridging ELISA method that is designed to detect the presence of anti-VAY736 antibodies in human serum was used.
    End point type
    Secondary
    End point timeframe
    Day 1, 29, 85, 169, 253 and 337
    End point values
    		 VAY736 Placebo
    Number of subjects analysed
    10
    15
    Units: Participants
        Day 1
    1
    3
        Day 29
    1
    2
        Day 85
    1
    1
        Day 169
    0
    2
        Day 253
    2
    1
        Day 337
    0
    0
    No statistical analyses for this end point

    Secondary: Ctrough of VAY736 from the serum concentration-time data

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    End point title
    		 Ctrough of VAY736 from the serum concentration-time data [6]
    End point description
    At pre-dose on Day 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309 and 337
    End point type
    Secondary
    End point timeframe
    At pre-dose on Day 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309 and 337
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only applicable for VAY736 arm
    End point values
    		 VAY736
    Number of subjects analysed
    11
    Units: nanogram (ng) / mililiter (mL)
    arithmetic mean (standard deviation)
        Day 1
    0.00 ± 0.00
        Day 29
    676.79 ± 499.931
        Day 57
    779.89 ± 645.363
        Day 85
    786.63 ± 501.225
        Day 113
    771.88 ± 623.268
        Day 141
    1316.05 ± 877.240
        Day 169
    1019.00 ± 587.097
        Day 197
    985.50 ± 495.652
        Day 225
    1271.10 ± 863.055
        Day 253
    998.57 ± 947.343
        Day 281
    705.00 ± 997.021
        Day 309
    827.40 ± 678.836
        Day 337
    688.50 ± 1172.12
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From start up to end of study, assessed up to approximately 2.4 years
    Adverse event reporting additional description
    Safety analyses were performed in the safety set including all participants who received at least one dose of any study drug
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    VAY736
    Reporting group description
    		 Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy

    Reporting group title
    Total
    Reporting group description
    		 Total

    Serious adverse events
    		 VAY736 Placebo Total
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 13 (38.46%)
    9 / 16 (56.25%)
    14 / 29 (48.28%)
         number of deaths (all causes)
    1
    0
    1
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Vasculitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Aortic valve incompetence
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 16 (6.25%)
    2 / 29 (6.90%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal vein occlusion
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Pancreatitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Hypoxia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Idiopathic pulmonary fibrosis
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 16 (6.25%)
    2 / 29 (6.90%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 13 (0.00%)
    3 / 16 (18.75%)
    3 / 29 (10.34%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    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
    		 VAY736 Placebo Total
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    13 / 13 (100.00%)
    15 / 16 (93.75%)
    28 / 29 (96.55%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Keratoacanthoma
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Dysplastic naevus
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Basal cell carcinoma
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    2
    0
    2
    Vascular disorders
    Hot flush
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 16 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    2
    0
    2
    Hypertension
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Chest discomfort
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Chest pain
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Fatigue
         subjects affected / exposed
    2 / 13 (15.38%)
    1 / 16 (6.25%)
    3 / 29 (10.34%)
         occurrences all number
    2
    2
    4
    Injection site bruising
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 16 (6.25%)
    2 / 29 (6.90%)
         occurrences all number
    1
    1
    2
    Injection site dermatitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    2
    0
    2
    Injection site erythema
         subjects affected / exposed
    2 / 13 (15.38%)
    1 / 16 (6.25%)
    3 / 29 (10.34%)
         occurrences all number
    2
    1
    3
    Injection site inflammation
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Injection site pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Injection site warmth
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Injection site rash
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Injection site pruritus
         subjects affected / exposed
    3 / 13 (23.08%)
    2 / 16 (12.50%)
    5 / 29 (17.24%)
         occurrences all number
    8
    2
    10
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 16 (6.25%)
    2 / 29 (6.90%)
         occurrences all number
    1
    1
    2
    Dysphonia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Cough
         subjects affected / exposed
    3 / 13 (23.08%)
    1 / 16 (6.25%)
    4 / 29 (13.79%)
         occurrences all number
    3
    1
    4
    Epistaxis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Idiopathic pulmonary fibrosis
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 16 (18.75%)
    4 / 29 (13.79%)
         occurrences all number
    1
    3
    4
    Hypoxia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Nasal congestion
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 16 (6.25%)
    2 / 29 (6.90%)
         occurrences all number
    1
    1
    2
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Insomnia
         subjects affected / exposed
    2 / 13 (15.38%)
    1 / 16 (6.25%)
    3 / 29 (10.34%)
         occurrences all number
    2
    1
    3
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 16 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    2
    0
    2
    Antinuclear antibody increased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Blood creatinine increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Blood creatine phosphokinase decreased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Blood glucose increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Blood parathyroid hormone decreased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Blood potassium increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Blood triglycerides increased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Blood urea increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Blood urine present
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Escherichia test positive
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Glucose urine present
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 16 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    2
    0
    2
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Mean cell volume increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Monocyte count increased
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 16 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    2
    0
    2
    Neutrophil count increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Protein urine present
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Urine albumin/creatinine ratio increased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    White blood cell count increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Weight decreased
         subjects affected / exposed
    1 / 13 (7.69%)
    4 / 16 (25.00%)
    5 / 29 (17.24%)
         occurrences all number
    1
    4
    5
    Urine analysis abnormal
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Urine protein/creatinine ratio increased
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 16 (6.25%)
    2 / 29 (6.90%)
         occurrences all number
    1
    1
    2
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 16 (6.25%)
    2 / 29 (6.90%)
         occurrences all number
    1
    1
    2
    Facial bones fracture
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Heat stroke
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Injection related reaction
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 16 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    4
    0
    4
    Sunburn
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 16 (12.50%)
    2 / 29 (6.90%)
         occurrences all number
    0
    2
    2
    Cardiac disorders
    Aortic valve incompetence
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Palpitations
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Tachycardia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Nervous system disorders
    Cognitive disorder
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Dizziness
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Cervical radiculopathy
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Headache
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 16 (12.50%)
    4 / 29 (13.79%)
         occurrences all number
    3
    2
    5
    Carotid artery stenosis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Paraesthesia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Memory impairment
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Tremor
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Blood and lymphatic system disorders
    Eosinophilia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Anaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Ear and labyrinth disorders
    Eustachian tube dysfunction
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Tinnitus
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Corneal degeneration
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Ocular hyperaemia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Diarrhoea
         subjects affected / exposed
    3 / 13 (23.08%)
    1 / 16 (6.25%)
    4 / 29 (13.79%)
         occurrences all number
    3
    1
    4
    Dyspepsia
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 16 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    2
    0
    2
    Enteritis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Flatulence
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Frequent bowel movements
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Nausea
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 16 (12.50%)
    3 / 29 (10.34%)
         occurrences all number
    1
    3
    4
    Vomiting
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 16 (12.50%)
    3 / 29 (10.34%)
         occurrences all number
    1
    2
    3
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Dermatitis atopic
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Drug eruption
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Hyperhidrosis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Keloid scar
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Photosensitivity reaction
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Pruritus
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    2
    2
    Rash erythematous
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Rash
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 16 (12.50%)
    2 / 29 (6.90%)
         occurrences all number
    0
    3
    3
    Skin lesion
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Pollakiuria
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Haematuria
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Urinary incontinence
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Back pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Limb discomfort
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Muscle spasms
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Osteoporosis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Musculoskeletal pain
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Pain in extremity
         subjects affected / exposed
    2 / 13 (15.38%)
    0 / 16 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    2
    0
    2
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 16 (12.50%)
    4 / 29 (13.79%)
         occurrences all number
    2
    3
    5
    Conjunctivitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Respiratory tract infection
         subjects affected / exposed
    2 / 13 (15.38%)
    1 / 16 (6.25%)
    3 / 29 (10.34%)
         occurrences all number
    2
    1
    3
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 16 (6.25%)
    2 / 29 (6.90%)
         occurrences all number
    2
    1
    3
    Influenza
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Tooth infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 16 (12.50%)
    4 / 29 (13.79%)
         occurrences all number
    5
    2
    7
    Urinary tract infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    2
    2
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 16 (6.25%)
    2 / 29 (6.90%)
         occurrences all number
    1
    1
    2
    Metabolism and nutrition disorders
    Vitamin D deficiency
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Hyperkalaemia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 16 (0.00%)
    1 / 29 (3.45%)
         occurrences all number
    1
    0
    1
    Decreased appetite
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 16 (6.25%)
    1 / 29 (3.45%)
         occurrences all number
    0
    1
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    30 Aug 2017
    This amendment corrected an inconsistency within the protocol around the potential need to follow-up partners of patients who could become pregnant during the study. At the time of this amendment, there were no patients enrolled
    23 Oct 2017
    This amendment clarified that the St. George’s Respiratory Questionnaire in IPF (SGRQ-I) was not available for use in all study countries planned in this study.
    08 Dec 2017
    This amendment addressed questions from MHRA upon their initial review of the study protocol.
    27 Feb 2018
    This amendment addressed questions from the Irish and French Health Authorities upon their initial reviews of the study protocol. In addition, the baseline visit was removed in order to reduce patient burden, as similar assessments were scheduled to be captured during Treatment Epoch Day 1
    03 Dec 2018
    This amendment corrected an error in the definition of a serious adverse event (SAE). The bullet formatting was corrected, and missing text was added to clarify when inpatient hospitalization or prolongation of an existing hospitalization was considered a SAE.
    10 Jul 2019
    The purpose of this amendment was to: (a) adjust the sample size and timing of the IA to align with clinical development strategy (b) reduce protocol complexity and (c) implement other minor updates throughout the protocol for clarity.
    27 Mar 2020
    This amendment revised the eligibility criteria with the aim of accelerating enrollment

    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.
    Due to EudraCT system limitations, data using 9999 as data points in this record are not an accurate representation of the results. Moreover, disposition in PK and PD/safety Follow-up Epochs could not be added. Please use https://www.novctrd.com
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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