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    Clinical Trial Results:
    A Phase 2 Trial to Evaluate the Efficacy of PRM-151 in Subjects with Idiopathic Pulmonary Fibrosis (IPF)

    Summary
    EudraCT number
    		 2014-004782-24
    Trial protocol
    		 DE   BE   CZ   ES   HU   IT  
    Global end of trial date
    03 Apr 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    10 Jun 2021
    First version publication date
    10 Jun 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    PRM-151-202
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02550873
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Promedior, Inc.: PRM-151-202
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    23 Nov 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    03 Apr 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Apr 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study randomized period was: determine the effect size of PRM-151 relative to placebo in change from Baseline to Week 28 in mean FVC [% predicted], pooling patients on a stable dose of pirfenidone or nintedanib and patients not on other treatment for IPF. The objectives of the open-label extension (OLE) were to analyze long-term safety and efficacy of PRM-151 over a 128-week period of exposure (RP + OLE).
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles that have their origins in the Declaration of Helsinki. All patients received information about the study and provided voluntary consent prior to conducting any study-related procedures. All executed originals of the ICFs were retained by the Investigator as part of the site study records. Copies of the signed ICFs were to be given to the patient or patient’s legally authorized representative.
    Background therapy
    		 The study population included both patients treated with a stable dose of pirfenidone or nintedanib and patients with no background pirfenidone or nintedanib therapy (either treatment naïve or discontinued prior to enrollment).
    Evidence for comparator
    		 -
    Actual start date of recruitment
    07 Sep 2015
    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
    Netherlands: 21
    Country: Number of subjects enrolled
    Spain: 1
    Country: Number of subjects enrolled
    Czechia: 6
    Country: Number of subjects enrolled
    Germany: 6
    Country: Number of subjects enrolled
    Italy: 9
    Country: Number of subjects enrolled
    Switzerland: 1
    Country: Number of subjects enrolled
    United States: 73
    Worldwide total number of subjects
    117
    EEA total number of subjects
    43
    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)
    31
    From 65 to 84 years
    86
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This study was conducted at 18 centers in the United States and the European Union.

    Pre-assignment
    Screening details
    		 151 patients were screened for the study. Of these, 117 were found to be eligible and were randomized. One patient dropped out of the study prior to receiving any study drug. 111 patients completed the randomized phase (RP) and entered the open-label extension (OLE).

    Period 1
    Period 1 title
    Randomized double-blind
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer
    Blinding implementation details
    All study personnel, with the exception of the unblinded site pharmacist, were blinded to the treatment allocation to which patients were randomized. This blinding was maintained during the dispensing of investigational product.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 PRM-151 treatment arm
    Arm description
    		 PRM-151 10 mg/kg IV infusion over 60 minutes days 1, 3, and 5, then one infusion every 4 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    PRM-151
    Investigational medicinal product code
    Other name
    Recombinant human pentraxin 2
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    PRM-151 10 mg/kg IV infusion over 60 minutes days 1, 3, and 5, then one infusion every 4 weeks

    Arm title
    		 Placebo arm
    Arm description
    		 Placebo IV infusion over 60 minutes on days 1, 3, and 5, then one infusion every 4 weeks
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo IV infusion over 60 minutes on days 1, 3, and 5, then one infusion every 4 weeks.

    Number of subjects in period 1 [1]
    		PRM-151 treatment arm Placebo arm
    Started
    77
    39
    Completed
    74
    37
    Not completed
    3
    2
         Adverse event, serious fatal
    -
    1
         Disease progression
    1
    1
         Adverse event, non-fatal
    2
    -
    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: 151 patients were screened for the study. Of these, 117 were found to be eligible and were randomized. One patient dropped out of the study prior to receiving any study drug, therefore only 116 subjects were included.
    Period 2
    Period 2 title
    Open-label extension
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ex-Placebo
    Arm description
    		 Patients who entered OLE and received placebo during RP
    Arm type
    		 Experimental

    Investigational medicinal product name
    PRM-151
    Investigational medicinal product code
    Other name
    Recombinant human pentraxin 2
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients who participated in the OLE received PRM-151 at a dose of 10 mg/kg as an IV infusion over 60 minutes on Days 1, 3, and 5, followed by 1 infusion every 4 weeks. Dosing on Days 1, 3, and 5 was repeated every 28 weeks during the OLE.

    Arm title
    		 Ex-Treated
    Arm description
    		 Patients who entered OLE and received PRM-151 during RP
    Arm type
    		 Experimental

    Investigational medicinal product name
    PRM-151
    Investigational medicinal product code
    Other name
    Recombinant human pentraxin 2
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Patients who participated in the OLE received PRM-151 at a dose of 10 mg/kg as an IV infusion over 60 minutes on Days 1, 3, and 5, followed by 1 infusion every 4 weeks. Dosing on Days 1, 3, and 5 was repeated every 28 weeks during the OLE.

    Number of subjects in period 2
    		Ex-Placebo Ex-Treated
    Started
    37
    74
    Completed
    20
    37
    Not completed
    17
    37
         Consent withdrawn by subject
    3
    16
         Sponsor's request
    1
    -
         Physician decision
    -
    1
         Adverse event, non-fatal
    7
    10
         Other
    1
    4
         Progression of disease
    5
    6

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    PRM-151 treatment arm
    Reporting group description
    		 PRM-151 10 mg/kg IV infusion over 60 minutes days 1, 3, and 5, then one infusion every 4 weeks

    Reporting group title
    Placebo arm
    Reporting group description
    		 Placebo IV infusion over 60 minutes on days 1, 3, and 5, then one infusion every 4 weeks

    Reporting group values
    		 PRM-151 treatment arm Placebo arm Total
    Number of subjects
    		 77 39 116
    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)
    		 20 11 31
        From 65-84 years
    		 57 28 85
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 69.03 ( 6.32 ) 67.62 ( 7.07 ) -
    Gender categorical
    Units: Subjects
        Female
    		 12 10 22
        Male
    		 65 29 94
    Ethnicity/Race
    Units: Subjects
        Caucasian
    		 74 39 113
        Black or African-American
    		 1 0 1
        Hispanic
    		 1 0 1
        Asian
    		 1 0 1
    IPF therapy status at baseline
    Units: Subjects
        Concurrent IPF therapy (Pirfenidone)
    		 39 22 61
        Concurrent IPF therapy (Nintedanib)
    		 22 8 30
        No concurrent IPF therapy (IPF therapy naive)
    		 8 7 15
        No concurrent IPF therapy (discontinued)
    		 8 2 10
    Comorbid conditions (GERD)
    Units: Subjects
        GERD present at baseline
    		 47 16 63
        no GERD at baseline
    		 30 23 53
    Comorbid conditions (Hypertension)
    Units: Subjects
        Hypertension present at baseline
    		 38 14 52
        No hypertension at baseline
    		 39 25 64
    Comorbid conditions (Cardiac disorders)
    Units: Subjects
        Cardiac disorders present at baseline
    		 29 7 36
        No cardiac disorders at baseline
    		 48 32 80
    Comorbid conditions (Coronary artery disease)
    Units: Subjects
        Coronary artery disease present at baseline
    		 12 4 16
        No coronary artery disease at baseline
    		 65 35 100
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    		 86.1 ( 15.2 ) 87.5 ( 13.4 ) -
    Time since diagnosis of IPF
    Units: years
        arithmetic mean (standard deviation)
    		 3.7 ( 2.2 ) 3.9 ( 2.6 ) -
    FVC
    Units: mL
        arithmetic mean (standard deviation)
    		 2733 ( 630 ) 2763 ( 654 ) -
    FEV1/FVC
    Units: percent
        arithmetic mean (standard deviation)
    		 81.2 ( 5.1 ) 81.6 ( 4.7 ) -
    Hemoglobin-corrected DLCO
    Units: percentage of predicted values
        arithmetic mean (standard deviation)
    		 40.1 ( 9.1 ) 43.2 ( 10.5 ) -
    6MWD
    Units: meters
        arithmetic mean (standard deviation)
    		 434.8 ( 92.5 ) 457.7 ( 117.7 ) -
    SpO2 at rest
    Units: percentage
        arithmetic mean (standard deviation)
    		 95.6 ( 2.1 ) 95.5 ( 1.8 ) -
    Baseline pentraxin 2 concentrations
    Units: ng/mL
        arithmetic mean (standard deviation)
    		 30456.17 ( 13566.81 ) 30961.54 ( 10090.47 ) -
    Subject analysis sets

    Subject analysis set title
    Placebo No Background Therapy
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    No background therapy placebo group

    Subject analysis set title
    PRM-151 No Background Therapy
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    No Background Therapy PRM-151 10 mg/kg IV group

    Subject analysis set title
    Placebo Pirfenidone or Nintendanib
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Pirfenidone or Nintendanib Placebo group

    Subject analysis set title
    PRM-151 Pirfenidone or Nintendanib
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Pirfenidone or Nintendanib PRM-151 10 mg/kg IV group

    Subject analysis sets values
    		 Placebo No Background Therapy PRM-151 No Background Therapy Placebo Pirfenidone or Nintendanib PRM-151 Pirfenidone or Nintendanib
    Number of subjects
    9
    16
    30
    61
    Age categorical
    Units: Subjects
        In utero
    0
    0
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
    0
    0
        Newborns (0-27 days)
    0
    0
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
    0
    0
        Children (2-11 years)
    0
    0
    0
    0
        Adolescents (12-17 years)
    0
    0
    0
    0
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    0
    0
    0
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Female
        Male
    Ethnicity/Race
    Units: Subjects
        Caucasian
        Black or African-American
        Hispanic
        Asian
    IPF therapy status at baseline
    Units: Subjects
        Concurrent IPF therapy (Pirfenidone)
        Concurrent IPF therapy (Nintedanib)
        No concurrent IPF therapy (IPF therapy naive)
        No concurrent IPF therapy (discontinued)
    Comorbid conditions (GERD)
    Units: Subjects
        GERD present at baseline
        no GERD at baseline
    Comorbid conditions (Hypertension)
    Units: Subjects
        Hypertension present at baseline
        No hypertension at baseline
    Comorbid conditions (Cardiac disorders)
    Units: Subjects
        Cardiac disorders present at baseline
        No cardiac disorders at baseline
    Comorbid conditions (Coronary artery disease)
    Units: Subjects
        Coronary artery disease present at baseline
        No coronary artery disease at baseline
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    Time since diagnosis of IPF
    Units: years
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    FVC
    Units: mL
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    FEV1/FVC
    Units: percent
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    Hemoglobin-corrected DLCO
    Units: percentage of predicted values
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    6MWD
    Units: meters
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    SpO2 at rest
    Units: percentage
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    Baseline pentraxin 2 concentrations
    Units: ng/mL
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    PRM-151 treatment arm
    Reporting group description
    		 PRM-151 10 mg/kg IV infusion over 60 minutes days 1, 3, and 5, then one infusion every 4 weeks

    Reporting group title
    Placebo arm
    Reporting group description
    		 Placebo IV infusion over 60 minutes on days 1, 3, and 5, then one infusion every 4 weeks
    Reporting group title
    Ex-Placebo
    Reporting group description
    		 Patients who entered OLE and received placebo during RP

    Reporting group title
    Ex-Treated
    Reporting group description
    		 Patients who entered OLE and received PRM-151 during RP

    Subject analysis set title
    Placebo No Background Therapy
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    No background therapy placebo group

    Subject analysis set title
    PRM-151 No Background Therapy
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    No Background Therapy PRM-151 10 mg/kg IV group

    Subject analysis set title
    Placebo Pirfenidone or Nintendanib
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Pirfenidone or Nintendanib Placebo group

    Subject analysis set title
    PRM-151 Pirfenidone or Nintendanib
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Pirfenidone or Nintendanib PRM-151 10 mg/kg IV group

    Primary: Change from Baseline to Week 28 in mean FVC [% predicted]

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    End point title
    		 Change from Baseline to Week 28 in mean FVC [% predicted]
    End point description
    Determine the effect size of PRM-151 relative to placebo in change from Baseline to Week 28 in mean FVC% predicted, pooling subjects on a stable dose of pirfenidone or nintedanib with subjects not on other treatment for IPF.
    End point type
    Primary
    End point timeframe
    Baseline to 28 week
    End point values
    		 PRM-151 treatment arm Placebo arm
    Number of subjects analysed
    77
    39
    Units: Percentage of predicted FVC
        arithmetic mean (standard error)
    -2.5 ( 0.42 )
    -4.8 ( 0.58 )
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Primary analysis was conducted on the All Treated Set (ATS) population (all randomized patients having received at least one administration of the study medication, allocated as randomized for analysis). The following statistical hypotheses were tested: • H0: Absence of difference between the treatment groups. • H1: A difference exists between the treatment groups.
    Comparison groups
    PRM-151 treatment arm v Placebo arm
    Number of subjects included in analysis
    116
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0014
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.1
         upper limit
    		 3.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.72

    Secondary: Change in 6-minute walk distance

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    End point title
    		 Change in 6-minute walk distance
    End point description
    Determine the effect size of PRM-151 relative to placebo on 6-minute walk distance (6MWD).
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 PRM-151 treatment arm Placebo arm
    Number of subjects analysed
    77
    39
    Units: meters
        arithmetic mean (standard error)
    -0.5 ( 4.92 )
    -31.8 ( 6.83 )
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    PRM-151 treatment arm v Placebo arm
    Number of subjects included in analysis
    116
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0002
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    31.3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 17.4
         upper limit
    		 45.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    8.42

    Secondary: Change in total lung volume on HRCT

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    End point title
    		 Change in total lung volume on HRCT
    End point description
    Mean change from Baseline to Week 28 in total lung volume, using quantitative imaging software, all treated set
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 Placebo No Background Therapy PRM-151 No Background Therapy Placebo Pirfenidone or Nintendanib PRM-151 Pirfenidone or Nintendanib
    Number of subjects analysed
    8
    14
    26
    52
    Units: mililiters
        arithmetic mean (standard error)
    -197.3 ( 86.66 )
    -103.8 ( 78.46 )
    -201.6 ( 62.41 )
    -108.1 ( 45.85 )
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    All patients from the ATS population who had HRCT data at both the Baseline and Week 28 time points
    Comparison groups
    PRM-151 No Background Therapy v Placebo Pirfenidone or Nintendanib v PRM-151 Pirfenidone or Nintendanib v Placebo No Background Therapy
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2032
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    93.5
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -27.7
         upper limit
    		 214.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    72.98

    Secondary: Change in volume of parenchymal features on HRCT (%), representative of ILA

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    End point title
    		 Change in volume of parenchymal features on HRCT (%), representative of ILA
    End point description
    Mean change from Baseline to Week 28 in volume of parenchymal features on HRCT (in % of total lung volume) representative of interstitial lung abnormalities (ILA) including ground glass density, reticular changes, and honeycombing, using quantitative imaging software.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 Placebo No Background Therapy PRM-151 No Background Therapy Placebo Pirfenidone or Nintendanib PRM-151 Pirfenidone or Nintendanib
    Number of subjects analysed
    8
    14
    26
    52
    Units: percentage
        arithmetic mean (standard error)
    1.5 ( 2.33 )
    2.6 ( 2.10 )
    1.9 ( 1.68 )
    3.0 ( 1.23 )
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Placebo No Background Therapy v PRM-151 No Background Therapy v Placebo Pirfenidone or Nintendanib v PRM-151 Pirfenidone or Nintendanib
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5835
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -2.2
         upper limit
    		 4.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.96

    Secondary: Change in volume of parenchymal features on HRCT (ml), representative of ILA

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    End point title
    		 Change in volume of parenchymal features on HRCT (ml), representative of ILA
    End point description
    Mean change from Baseline to Week 28 in volume of parenchymal features on HRCT (in ml) representative of interstitial lung abnormalities (ILA) including ground glass density, reticular changes, and honeycombing, using quantitative imaging software.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 Placebo No Background Therapy PRM-151 No Background Therapy Placebo Pirfenidone or Nintendanib PRM-151 Pirfenidone or Nintendanib
    Number of subjects analysed
    8
    14
    26
    52
    Units: mililiters
        arithmetic mean (standard error)
    17.8 ( 55.26 )
    49.7 ( 49.65 )
    49.0 ( 39.64 )
    80.9 ( 29.21 )
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Placebo No Background Therapy v PRM-151 No Background Therapy v Placebo Pirfenidone or Nintendanib v PRM-151 Pirfenidone or Nintendanib
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4927
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    31.9
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -45
         upper limit
    		 108.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    46.33

    Secondary: Change from in volume of parenchymal features on HRCT (in %) non-ILA

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    End point title
    		 Change from in volume of parenchymal features on HRCT (in %) non-ILA
    End point description
    Mean change from Baseline to Week 28 in volume of parenchymal features on HRCT (in % of total lung volume) representative of normal lung (non-ILA), including normal and mild low attenuation areas, using quantitative imaging software.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 Placebo No Background Therapy PRM-151 No Background Therapy Placebo Pirfenidone or Nintendanib PRM-151 Pirfenidone or Nintendanib
    Number of subjects analysed
    8
    14
    26
    52
    Units: Percentage of total lung volume
        arithmetic mean (standard error)
    -1.4 ( 2.27 )
    -2.6 ( 2.05 )
    -2.1 ( 1.64 )
    -3.3 ( 1.20 )
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Placebo No Background Therapy v PRM-151 No Background Therapy v Placebo Pirfenidone or Nintendanib v PRM-151 Pirfenidone or Nintendanib
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5196
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -4.4
         upper limit
    		 1.9
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.91

    Secondary: Change in volume of parenchymal features on HRCT (ml), non-ILA

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    End point title
    		 Change in volume of parenchymal features on HRCT (ml), non-ILA
    End point description
    Mean change from Baseline to Week 28 in volume of parenchymal features on HRCT (in ml) representative of normal lung (non-ILA), including normal and mild low attenuation areas, using quantitative imaging software.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 Placebo No Background Therapy PRM-151 No Background Therapy Placebo Pirfenidone or Nintendanib PRM-151 Pirfenidone or Nintendanib
    Number of subjects analysed
    8
    14
    26
    52
    Units: mililiters
        arithmetic mean (standard error)
    -208.8 ( 121.20 )
    -165.2 ( 109.58 )
    -244.7 ( 87.45 )
    -201.1 ( 64.16 )
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Placebo No Background Therapy v PRM-151 No Background Therapy v Placebo Pirfenidone or Nintendanib v PRM-151 Pirfenidone or Nintendanib
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6707
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    43.6
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -126.3
         upper limit
    		 213.5
    Variability estimate
    Standard error of the mean
    Dispersion value
    102.28

    Secondary: Correlation between Change from Baseline to Week 28 in FVC (%) and Change from Baseline to Week 28 in Total Lung Volume (mL)

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    End point title
    		 Correlation between Change from Baseline to Week 28 in FVC (%) and Change from Baseline to Week 28 in Total Lung Volume (mL)
    End point description
    Correlation between mean change from Baseline to Week 28 in FVC [% predicted] and mean change from Baseline to Week 28 in total lung volume (in ml) representative of interstitial lung abnormalities (ILA), including ground glass density, reticular changes, and honeycombing by quantitative imaging software.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 PRM-151 treatment arm Placebo arm
    Number of subjects analysed
    60
    33
    Units: Correlation coefficient
        number (confidence interval 95%)
    0.3776 (0.1337 to 0.5741)
    0.6788 (0.4288 to 0.8256)
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    PRM-151 treatment arm v Placebo arm
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    P-value
    		 < 0.0001
    Method
    		 Clopper-Pearson
    Confidence interval
    Notes
    [1] - correlation analysis

    Secondary: Correlation between Change from Baseline to Week 28 in FVC (%) and Change from Baseline to Week 28 in Interstitial Lung Abnormalities (mL)

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    End point title
    		 Correlation between Change from Baseline to Week 28 in FVC (%) and Change from Baseline to Week 28 in Interstitial Lung Abnormalities (mL)
    End point description
    Correlation between mean change from Baseline to Week 28 in FVC [% predicted] and mean change from Baseline to Week 28 in volume of parenchymal features on HRCT (in % of total lung volume) representative of interstitial lung abnormalities (ILA), including ground glass density, reticular changes, and honeycombing by quantitative imaging software.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 PRM-151 treatment arm Placebo arm
    Number of subjects analysed
    60
    33
    Units: Correlation coefficient
        number (confidence interval 95%)
    -0.5027 (-0.6686 to -0.2812)
    -0.4570 (-0.6880 to -0.1279)
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    PRM-151 treatment arm v Placebo arm
    Number of subjects included in analysis
    93
    Analysis specification
    Pre-specified
    Analysis type
    		 other [2]
    P-value
    		 < 0.0001
    Method
    		 Clopper-Pearson
    Confidence interval
    Notes
    [2] - Correlation analysis

    Secondary: Proportion of subjects with a decline in FVC [% predicted] of ≥ 5% and ≥10% from baseline to week 28

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    End point title
    		 Proportion of subjects with a decline in FVC [% predicted] of ≥ 5% and ≥10% from baseline to week 28
    End point description
    Pulmonary Function Tests for the proportion (%) of subjects with a decline in FVC [% predicted] of ≥5% and ≥10% from baseline to week 28
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 Placebo No Background Therapy PRM-151 No Background Therapy Placebo Pirfenidone or Nintendanib PRM-151 Pirfenidone or Nintendanib
    Number of subjects analysed
    8
    13
    27
    54
    Units: Subjects
    number (not applicable)
        Decline in % Predicted FVC ≥ 5%
    2
    2
    11
    18
        Decline in % Predicted FVC ≥ 10%
    0
    1
    3
    1
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    for decline in % Predicted FVC ≥ 5%
    Comparison groups
    Placebo No Background Therapy v PRM-151 No Background Therapy v Placebo Pirfenidone or Nintendanib v PRM-151 Pirfenidone or Nintendanib
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4179 [3]
    Method
    		 Mixed models analysis
    Confidence interval
    Notes
    [3] - for decline in % Predicted FVC ≥ 5%
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    for decline in % predicted FVC ≥ 10%
    Comparison groups
    Placebo No Background Therapy v PRM-151 No Background Therapy v Placebo Pirfenidone or Nintendanib v PRM-151 Pirfenidone or Nintendanib
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2184 [4]
    Method
    		 Mixed models analysis
    Confidence interval
    Notes
    [4] - for decline in % predicted FVC ≥ 10%

    Secondary: Proportion of subjects with a decline in FVC [ml] of ≥ 100ml and ≥ 200ml from baseline to week 28.

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    End point title
    		 Proportion of subjects with a decline in FVC [ml] of ≥ 100ml and ≥ 200ml from baseline to week 28.
    End point description
    Pulmonary Function Tests for the Proportion (%) of subjects with a decline in FVC [ml] of ≥ 100ml and ≥ 200ml from baseline to week 28.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 Placebo No Background Therapy PRM-151 No Background Therapy Placebo Pirfenidone or Nintendanib PRM-151 Pirfenidone or Nintendanib
    Number of subjects analysed
    8
    13
    27
    54
    Units: Subjects
    number (not applicable)
        Decline in FVC ≥100 mL
    2
    5
    16
    32
        Decline in FVC ≥200 mL
    1
    2
    8
    19
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    for decline in FVC ≥ 100 mL
    Comparison groups
    Placebo No Background Therapy v PRM-151 No Background Therapy v Placebo Pirfenidone or Nintendanib v PRM-151 Pirfenidone or Nintendanib
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5976 [5]
    Method
    		 Mixed models analysis
    Confidence interval
    Notes
    [5] - for decline in FVC ≥ 100 mL
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    for decline in FVC ≥ 200 mL
    Comparison groups
    Placebo No Background Therapy v PRM-151 No Background Therapy v Placebo Pirfenidone or Nintendanib v PRM-151 Pirfenidone or Nintendanib
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.5976 [6]
    Method
    		 Mixed models analysis
    Confidence interval
    Notes
    [6] - for decline in FVC ≥ 200 mL

    Secondary: Proportion of subjects with an increase in FVC [% predicted] of ≥ 5% and ≥ 10% from baseline to week 28

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    End point title
    		 Proportion of subjects with an increase in FVC [% predicted] of ≥ 5% and ≥ 10% from baseline to week 28
    End point description
    Pulmonary Function Tests for the Proportion (%) of subjects with an increase in FVC [% predicted] of ≥5% and ≥ 10% from baseline to week 28.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 Placebo No Background Therapy PRM-151 No Background Therapy Placebo Pirfenidone or Nintendanib PRM-151 Pirfenidone or Nintendanib
    Number of subjects analysed
    8
    13
    27
    54
    Units: Subjects
    number (not applicable)
        Increase in % Predicted FVC ≥5%
    0
    1
    0
    1
        Increase in % Predicted FVC ≥10%
    0
    0
    0
    0
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    for increase in % predicted FVC ≥ 5%
    Comparison groups
    Placebo No Background Therapy v PRM-151 No Background Therapy v Placebo Pirfenidone or Nintendanib v PRM-151 Pirfenidone or Nintendanib
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2912 [7]
    Method
    		 Mixed models analysis
    Confidence interval
    Notes
    [7] - for increase in % predicted FVC ≥ 5%

    Secondary: Proportion of subjects with an increase in FVC [ml] of ≥ 100 ml and ≥ 200 ml from baseline to week 28

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    End point title
    		 Proportion of subjects with an increase in FVC [ml] of ≥ 100 ml and ≥ 200 ml from baseline to week 28
    End point description
    Pulmonary Function Tests for the Proportion of subjects with an increase in FVC [ml] of ≥ 100 ml and ≥200 ml from baseline to week 28
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 Placebo No Background Therapy PRM-151 No Background Therapy Placebo Pirfenidone or Nintendanib PRM-151 Pirfenidone or Nintendanib
    Number of subjects analysed
    8
    13
    27
    54
    Units: Subjects
    number (not applicable)
        Increase in FVC ≥100 mL
    0
    1
    0
    6
        Increase in FVC ≥200 mL
    0
    0
    0
    0
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    for increase in FVC ≥ 100 mL
    Comparison groups
    PRM-151 No Background Therapy v Placebo Pirfenidone or Nintendanib v PRM-151 Pirfenidone or Nintendanib v Placebo No Background Therapy
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0508 [8]
    Method
    		 Mixed models analysis
    Confidence interval
    Notes
    [8] - for increase in FVC ≥ 100 mL

    Secondary: Proportion of subjects with stable disease by FVC [% predicted], defined as a change in FVC [% predicted] of < 5% from baseline to week 28

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    End point title
    		 Proportion of subjects with stable disease by FVC [% predicted], defined as a change in FVC [% predicted] of < 5% from baseline to week 28
    End point description
    Pulmonary Function Tests for the Proportion of subjects with stable disease by FVC [% predicted], defined as a change in FVC [% predicted] of < 5% from baseline to week 28.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 Placebo No Background Therapy PRM-151 No Background Therapy Placebo Pirfenidone or Nintendanib PRM-151 Pirfenidone or Nintendanib
    Number of subjects analysed
    8
    13
    27
    54
    Units: Subjects
        number (not applicable)
    6
    10
    16
    35
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Placebo No Background Therapy v PRM-151 No Background Therapy v Placebo Pirfenidone or Nintendanib v PRM-151 Pirfenidone or Nintendanib
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6308
    Method
    		 Mixed models analysis
    Confidence interval

    Secondary: Proportion of subjects with stable disease by FVC in ml, defined as a change in FVC of < 100ml from Baseline to week 28

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    End point title
    		 Proportion of subjects with stable disease by FVC in ml, defined as a change in FVC of < 100ml from Baseline to week 28
    End point description
    Pulmonary function tests for the Proportion of subjects with stable disease by FVC in ml, defined as a change in FVC of < 100ml from Baseline to week 28.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 Placebo No Background Therapy PRM-151 No Background Therapy Placebo Pirfenidone or Nintendanib PRM-151 Pirfenidone or Nintendanib
    Number of subjects analysed
    8
    13
    27
    54
    Units: Subjects
        number (not applicable)
    6
    7
    11
    16
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Placebo No Background Therapy v PRM-151 No Background Therapy v Placebo Pirfenidone or Nintendanib v PRM-151 Pirfenidone or Nintendanib
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1846
    Method
    		 Mixed models analysis
    Confidence interval

    Secondary: Change in % predicted Hb-corrected DLCO

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    End point title
    		 Change in % predicted Hb-corrected DLCO
    End point description
    Mean change from Baseline to Week 28 in Hb-corrected DLCO i.e., diffusion capacity of carbon monoxide [% predicted].
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 Placebo No Background Therapy PRM-151 No Background Therapy Placebo Pirfenidone or Nintendanib PRM-151 Pirfenidone or Nintendanib
    Number of subjects analysed
    9
    16
    30
    61
    Units: Percentage
        arithmetic mean (standard error)
    -2.4 ( 1.60 )
    -2.8 ( 1.39 )
    -2.5 ( 1.10 )
    -3.0 ( 0.84 )
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    PRM-151 No Background Therapy v Placebo Pirfenidone or Nintendanib v Placebo No Background Therapy v PRM-151 Pirfenidone or Nintendanib
    Number of subjects included in analysis
    116
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7424
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -2.6
         upper limit
    		 1.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.31

    Secondary: The Incidence of TEAEs

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    End point title
    		 The Incidence of TEAEs
    End point description
    Any Treatment-Emergent Adverse Event (TEAE), SAF population
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 PRM-151 treatment arm Placebo arm
    Number of subjects analysed
    77
    39
    Units: Subjects
        number (not applicable)
    71
    36
    No statistical analyses for this end point

    Secondary: The Incidence of TESAEs

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    End point title
    		 The Incidence of TESAEs
    End point description
    Serious TEAEs, SAF population
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 PRM-151 treatment arm Placebo arm
    Number of subjects analysed
    77
    39
    Units: Subjects
        number (not applicable)
    6
    4
    No statistical analyses for this end point

    Secondary: The Incidence of Respiratory Decline TEAEs

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    End point title
    		 The Incidence of Respiratory Decline TEAEs
    End point description
    Incidence of respiratory TEAEs, SAF population “Respiratory decline” events are defined as follows: - Unscheduled visits to a healthcare professional for respiratory status deterioration. - Urgent care visit for respiratory status deterioration. - Hospitalization due to a worsening or exacerbation of respiratory symptoms.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 PRM-151 treatment arm Placebo arm
    Number of subjects analysed
    77
    39
    Units: Subjects
        number (not applicable)
    11
    4
    No statistical analyses for this end point

    Secondary: The Incidence of Respiratory Decline TESAEs

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    End point title
    		 The Incidence of Respiratory Decline TESAEs
    End point description
    Incidence of respiratory serious TEAEs, SAF population “Respiratory decline” events are defined as follows: - Unscheduled visits to a healthcare professional for respiratory status deterioration. - Urgent care visit for respiratory status deterioration. - Hospitalization due to a worsening or exacerbation of respiratory symptoms.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 PRM-151 treatment arm Placebo arm
    Number of subjects analysed
    77
    39
    Units: Subjects
        number (not applicable)
    4
    4
    No statistical analyses for this end point

    Secondary: The proportion of subjects discontinuing study drug due to TEAEs

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    End point title
    		 The proportion of subjects discontinuing study drug due to TEAEs
    End point description
    TEAEs Leading to Permanent Discontinuation of Study Drug
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 PRM-151 treatment arm Placebo arm
    Number of subjects analysed
    77
    39
    Units: Subjects
        number (not applicable)
    2
    1
    No statistical analyses for this end point

    Secondary: All cause mortality

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    End point title
    		 All cause mortality
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 PRM-151 treatment arm Placebo arm
    Number of subjects analysed
    77
    39
    Units: Subjects
        number (not applicable)
    0
    1
    No statistical analyses for this end point

    Secondary: Mortality due to respiratory deterioration

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    End point title
    		 Mortality due to respiratory deterioration
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline to Week 28
    End point values
    		 PRM-151 treatment arm Placebo arm
    Number of subjects analysed
    77
    39
    Units: Subjects
        number (not applicable)
    0
    1
    No statistical analyses for this end point

    Other pre-specified: Change in FVC (% predicted) - OLE

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    End point title
    		 Change in FVC (% predicted) - OLE
    End point description
    End point type
    Other pre-specified
    End point timeframe
    Baseline to Week 52 (OLE)
    End point values
    		 Ex-Placebo Ex-Treated
    Number of subjects analysed
    37
    74
    Units: Percentage of predicted FVC
        arithmetic mean (standard error)
    -5.0 ( 0.48 )
    -3.7 ( 0.34 )
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Ex-Placebo v Ex-Treated
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0199
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 2.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.59

    Other pre-specified: Change in FVC (ml) - OLE

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    End point title
    		 Change in FVC (ml) - OLE
    End point description
    End point type
    Other pre-specified
    End point timeframe
    Baseline to Week 52 (OLE)
    End point values
    		 Ex-Placebo Ex-Treated
    Number of subjects analysed
    37
    74
    Units: mililiters
        arithmetic mean (standard error)
    -229.5 ( 19.42 )
    -179.9 ( 13.64 )
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Ex-Treated v Ex-Placebo
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0365
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    49.7
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 10.6
         upper limit
    		 88.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    23.73

    Other pre-specified: Change in 6-minute walk distance (OLE)

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    End point title
    		 Change in 6-minute walk distance (OLE)
    End point description
    End point type
    Other pre-specified
    End point timeframe
    Baseline to Week 52 (OLE)
    End point values
    		 Ex-Placebo Ex-Treated
    Number of subjects analysed
    37
    74
    Units: meters
        arithmetic mean (standard error)
    -29.0 ( 5.74 )
    -10.6 ( 4.09 )
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Ex-Placebo v Ex-Treated
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0089
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Point estimate
    18.5
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 6.9
         upper limit
    		 30.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.05

    Other pre-specified: Number of subjects with adverse events emerging during the OLE

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    End point title
    		 Number of subjects with adverse events emerging during the OLE
    End point description
    Number of subjects with Treatment-Emergent Adverse Events Emerging During the Open-Label Extension up to and Including Week 128 (SAF-OLE Population)
    End point type
    Other pre-specified
    End point timeframe
    After the first dose in the OLE and through Week 128
    End point values
    		 Ex-Placebo Ex-Treated
    Number of subjects analysed
    37
    74
    Units: Subjects
        Any TEAE
    36
    69
        Any TEAE leading to permanent study drug discontin
    10
    18
        Any TEAE leading to permanent study discontinuatio
    7
    10
        Any TEAE leading to hospitalization
    13
    25
        Any mild TEAE
    31
    65
        Any moderate TEAE
    28
    53
        Any severe TEAE
    8
    23
        Any life-threatening TEAE
    2
    1
        Any TEAE possibly or probably related to study dru
    14
    24
        Any infusion-related reaction TEAE
    3
    7
        Any respiratory decline TEAE
    8
    31
        Any TEAE in the HLT of Liver Function Analyses
    1
    2
        Any TEAE in the SOC of Renal and urinary disorders
    4
    9
        Any IPF exacerbations reported as TEAEs
    1
    6
        Any serious TEAE
    15
    32
        Any mild serious TEAE
    1
    1
        Any moderate serious TEAE
    6
    10
        Any severe serious TEAE
    7
    20
        Any life-threatening serious TEAE
    2
    1
        Death
    4
    10
        Any serious TEAE leading to permanent study drug d
    10
    14
        Any serious TEAE leading to permanent study discon
    6
    7
        Any serious TEAE leading to hospitalization
    13
    25
        Any serious TEAE possibly or probably related to s
    1
    1
        Any infusion-related reaction serious TEAE
    0
    1
        Any respiratory decline serious TEAE
    6
    16
        Any serious TEAE in the HLT of Liver Function Anal
    0
    0
        Any serious TEAE in the SOC of Renal and urinary d
    1
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    RP - 28 weeks OLE - TEAEs occurring after the first dose in the OLE and through Week 128 are included.
    Adverse event reporting additional description
    RP - All AEs from signing of informed consent until last study visit were entered in the database, but only AEs from the time of first study treatment dose administered to the patient (TEAEs) until last study visit were analysed. OLE - TEAEs occurring after the first dose in the OLE and through Week 128 are included.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    PRM-151 treatment arm (RP)
    Reporting group description
    		 PRM-151 10 mg/kg IV infusion over 60 minutes days 1, 3, and 5, then one infusion every 4 weeks

    Reporting group title
    Placebo arm (RP)
    Reporting group description
    		 Placebo IV infusion over 60 minutes on days 1, 3, and 5, then one infusion every 4 weeks

    Reporting group title
    Ex-placebo (OLE)
    Reporting group description
    		 -

    Reporting group title
    Ex-treated (OLE)
    Reporting group description
    		 -

    Serious adverse events
    		 PRM-151 treatment arm (RP) Placebo arm (RP) Ex-placebo (OLE) Ex-treated (OLE)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 77 (7.79%)
    4 / 39 (10.26%)
    15 / 37 (40.54%)
    32 / 74 (43.24%)
         number of deaths (all causes)
    0
    1
    6
    10
         number of deaths resulting from adverse events
    0
    1
    6
    10
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    B-cell lymphoma
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma metastatic
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma stage I
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastases to lymph nodes
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small cell lung cancer extensive stage
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of the tongue
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Carotid artery stenosis
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Surgical and medical procedures
    Alcohol detoxification
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung transplant
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary Embolism
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Idiopathic Pulmonary Fibrosis
         subjects affected / exposed
    1 / 77 (1.30%)
    2 / 39 (5.13%)
    3 / 37 (8.11%)
    8 / 74 (10.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 4
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 4
    0 / 4
    Dyspnoea
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 39 (2.56%)
    0 / 37 (0.00%)
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumomediastinum
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Transplant evaluation
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Rib fracture
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Coronary Artery Disease
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial Fibrillation
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 39 (2.56%)
    0 / 37 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    Acute coronary syndrome
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia supraventricular
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Palpitations
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Embolic Cerebral Infarction
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysgeusia
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Tendonitis
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 39 (2.56%)
    2 / 37 (5.41%)
    5 / 74 (6.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    Lower Respiratory Tract Infection
         subjects affected / exposed
    1 / 77 (1.30%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory Tract Infection
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 39 (2.56%)
    1 / 37 (2.70%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 77 (0.00%)
    1 / 39 (2.56%)
    0 / 37 (0.00%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bursitis infective
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metapneumovirus infection
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    0 / 74 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    0 / 37 (0.00%)
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 PRM-151 treatment arm (RP) Placebo arm (RP) Ex-placebo (OLE) Ex-treated (OLE)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    71 / 77 (92.21%)
    36 / 39 (92.31%)
    36 / 37 (97.30%)
    69 / 74 (93.24%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    2 / 37 (5.41%)
    6 / 74 (8.11%)
         occurrences all number
    0
    0
    3
    9
    Blood pressure fluctuation
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    3 / 37 (8.11%)
    4 / 74 (5.41%)
         occurrences all number
    0
    0
    3
    6
    Nervous system disorders
    Headache
         subjects affected / exposed
    11 / 77 (14.29%)
    3 / 39 (7.69%)
    1 / 37 (2.70%)
    5 / 74 (6.76%)
         occurrences all number
    15
    6
    1
    7
    Dizziness
         subjects affected / exposed
    6 / 77 (7.79%)
    3 / 39 (7.69%)
    2 / 37 (5.41%)
    10 / 74 (13.51%)
         occurrences all number
    7
    4
    2
    13
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    13 / 77 (16.88%)
    4 / 39 (10.26%)
    5 / 37 (13.51%)
    14 / 74 (18.92%)
         occurrences all number
    20
    4
    5
    18
    Oedema peripheral
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    4 / 37 (10.81%)
    3 / 74 (4.05%)
         occurrences all number
    0
    0
    4
    4
    Pyrexia
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    3 / 37 (8.11%)
    3 / 74 (4.05%)
         occurrences all number
    0
    0
    3
    3
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    9 / 77 (11.69%)
    2 / 39 (5.13%)
    2 / 37 (5.41%)
    15 / 74 (20.27%)
         occurrences all number
    11
    2
    2
    26
    Nausea
         subjects affected / exposed
    5 / 77 (6.49%)
    2 / 39 (5.13%)
    1 / 37 (2.70%)
    6 / 74 (8.11%)
         occurrences all number
    6
    2
    1
    8
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    2 / 37 (5.41%)
    5 / 74 (6.76%)
         occurrences all number
    0
    0
    2
    6
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    14 / 77 (18.18%)
    2 / 39 (5.13%)
    14 / 37 (37.84%)
    16 / 74 (21.62%)
         occurrences all number
    16
    2
    26
    22
    Idiopathic pulmonary fibrosis
         subjects affected / exposed
    11 / 77 (14.29%)
    5 / 39 (12.82%)
    11 / 37 (29.73%)
    22 / 74 (29.73%)
         occurrences all number
    11
    6
    18
    34
    Dyspnoea
         subjects affected / exposed
    7 / 77 (9.09%)
    4 / 39 (10.26%)
    6 / 37 (16.22%)
    26 / 74 (35.14%)
         occurrences all number
    8
    4
    11
    34
    Productive cough
         subjects affected / exposed
    3 / 77 (3.90%)
    3 / 39 (7.69%)
    1 / 37 (2.70%)
    9 / 74 (12.16%)
         occurrences all number
    3
    3
    1
    10
    Hypoxia
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    5 / 37 (13.51%)
    11 / 74 (14.86%)
         occurrences all number
    0
    0
    7
    12
    Pulmonary hypertension
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    4 / 37 (10.81%)
    6 / 74 (8.11%)
         occurrences all number
    0
    0
    6
    8
    Dyspnoea exertional
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    8 / 74 (10.81%)
         occurrences all number
    0
    0
    1
    9
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    1 / 37 (2.70%)
    7 / 74 (9.46%)
         occurrences all number
    0
    0
    1
    7
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    4 / 77 (5.19%)
    3 / 39 (7.69%)
    2 / 37 (5.41%)
    4 / 74 (5.41%)
         occurrences all number
    5
    4
    3
    4
    Back pain
         subjects affected / exposed
    3 / 77 (3.90%)
    4 / 39 (10.26%)
    3 / 37 (8.11%)
    8 / 74 (10.81%)
         occurrences all number
    3
    8
    3
    8
    Arthralgia
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    4 / 37 (10.81%)
    8 / 74 (10.81%)
         occurrences all number
    0
    0
    6
    16
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    12 / 77 (15.58%)
    9 / 39 (23.08%)
    5 / 37 (13.51%)
    13 / 74 (17.57%)
         occurrences all number
    15
    13
    8
    24
    Bronchitis
         subjects affected / exposed
    8 / 77 (10.39%)
    5 / 39 (12.82%)
    8 / 37 (21.62%)
    8 / 74 (10.81%)
         occurrences all number
    8
    5
    10
    9
    Upper respiratory tract infection
         subjects affected / exposed
    7 / 77 (9.09%)
    5 / 39 (12.82%)
    8 / 37 (21.62%)
    18 / 74 (24.32%)
         occurrences all number
    7
    5
    11
    21
    Respiratory tract infection
         subjects affected / exposed
    4 / 77 (5.19%)
    2 / 39 (5.13%)
    2 / 37 (5.41%)
    9 / 74 (12.16%)
         occurrences all number
    5
    2
    3
    11
    Sinusitis
         subjects affected / exposed
    3 / 77 (3.90%)
    3 / 39 (7.69%)
    3 / 37 (8.11%)
    3 / 74 (4.05%)
         occurrences all number
    3
    4
    3
    3
    Influenza
         subjects affected / exposed
    3 / 77 (3.90%)
    3 / 39 (7.69%)
    2 / 37 (5.41%)
    4 / 74 (5.41%)
         occurrences all number
    3
    3
    2
    4
    Pneumonia
         subjects affected / exposed
    0 / 77 (0.00%)
    0 / 39 (0.00%)
    3 / 37 (8.11%)
    9 / 74 (12.16%)
         occurrences all number
    0
    0
    4
    10
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    4 / 77 (5.19%)
    2 / 39 (5.13%)
    0 / 37 (0.00%)
    0 / 74 (0.00%)
         occurrences all number
    4
    2
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Feb 2016
    1)Clarification regarding WOCBP birth control 2) Addition of inclusion criterion re lung transplantation 3) Clarification of inclusion criterion re background treatment 4) revision of inclusion criterion re 6MWT 5)Revision of exclusion criterion re immuno-suppressants 6) Exclusion criterion re pregnant/lactating patient 7)Addition to Schedule of Events 8)Change in infusion time 9) Addition to Study Procedures
    03 Mar 2016
    minor updates

    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.
    Sample size was not appropriate to explore additional hypotheses beyond the prespecified primary analyses; diagnosis of IPF is allowing for “possible usual interstitial pneumonia”; HRCT was not centrally read; HRCT susceptible to potential artifacts;

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/29800034
    http://www.ncbi.nlm.nih.gov/pubmed/31122893
    For support, Contact us.
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    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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