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    Clinical Trial Results:
    A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Biological Activity, and PK of ND-L02-s0201 in Subjects with Idiopathic Pulmonary Fibrosis (IPF)

    Summary
    EudraCT number
    		 2017-004919-39
    Trial protocol
    		 DE  
    Global end of trial date
    24 Aug 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    29 Dec 2023
    First version publication date
    29 Dec 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    ND-L02-s0201-005
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03538301
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Nitto Denko Corporation
    Sponsor organisation address
    1-1-2, Shimohozumi, Ibaraki, Osaka, Japan, 567-8680
    Public contact
    Nitto Denko Corporation Study Director, Nitto Denko Corporation, clinicaltrialinfo005@nitto.com
    Scientific contact
    Nitto Denko Corporation Study Director, Nitto Denko Corporation, clinicaltrialinfo005@nitto.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
    24 Aug 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    24 Aug 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Aug 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Evaluate the safety and tolerability of ND-L02-s0201, administered at 2 dose levels, every 2 weeks over 24 weeks, versus placebo, in conjunction with standard of care (SOC)
    Protection of trial subjects
    To ensure safety of the overall study an independent Data Monitoring Committee (DMC) was established. The DMC periodically reviewed the safety and tolerability of study treatment for the duration of the study. The DMC included a chairperson and pulmonologist who were experienced in idiopathic pulmonary fibrosis; all members were experienced with clinical trials and evaluating adverse events, and would not otherwise participate in the study. The DMC also included an independent statistician.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Jun 2018
    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
    Japan: 20
    Country: Number of subjects enrolled
    United States: 89
    Country: Number of subjects enrolled
    United Kingdom: 6
    Country: Number of subjects enrolled
    Germany: 8
    Worldwide total number of subjects
    123
    EEA total number of subjects
    8
    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)
    27
    From 65 to 84 years
    96
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Diagnosis of idiopathic pulmonary fibrosis within 5 years before Visit 1a, confirmed by the Principal Investigator (PI) using American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) guidelines

    Period 1
    Period 1 title
    Overall Study (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
    Blinding implementation details
    There was the potential for infusion-related reaction in a small percentage of participants receiving ND-L02-s0201 for Injection. Sites were expected to ensure the extent of unblinding did not go beyond the individuals who evaluated a participant with a possible infusion-related reaction or documented this information into the participant's casebook. Unblinded information should not have been documented in the participant's casebook.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Intravenous placebo infusion every 2 weeks (± 4 days for Visit 3 or ± 7 days for Visits 4 to 13, ensuring a minimum of 7 days between each dose) for a total of 12 doses.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Injection
    Dosage and administration details
    Sodium Chloride 0.9% for Injection

    Arm title
    		 ND-L02-s0201 45 mg
    Arm description
    		 ND-L02-s0201: 45 mg intravenous administration every 2 weeks (± 4 days for Visit 3 or ± 7 days for Visits 4 to 13, ensuring a minimum of 7 days between each dose) for a total of 12 doses.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ND-L02-s0201
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Injection
    Dosage and administration details
    45 mg ND-L02-s0201 for injection administered once every 2 weeks over a 24-week duration (a total of 12 doses).

    Arm title
    		 ND-L02-s0201 90 mg
    Arm description
    		 ND-L02-s0201: 90 mg intravenous administration every 2 weeks (± 4 days for Visit 3 or ± 7 days for Visits 4 to 13, ensuring a minimum of 7 days between each dose) for a total of 12 doses.
    Arm type
    		 Experimental

    Investigational medicinal product name
    ND-L02-s0201
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Injection
    Dosage and administration details
    90 mg ND-L02-s0201 for injection administered once every 2 weeks over a 24-week duration (a total of 12 doses).

    Number of subjects in period 1
    		Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Started
    42
    41
    40
    Completed
    31
    29
    28
    Not completed
    11
    12
    12
         Adverse event, serious fatal
    1
    1
    -
         Physician decision
    -
    1
    -
         Adverse event, non-fatal
    1
    4
    4
         Terminated Early due to COVID-19 impact
    9
    6
    7
         Protocol deviation
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Intravenous placebo infusion every 2 weeks (± 4 days for Visit 3 or ± 7 days for Visits 4 to 13, ensuring a minimum of 7 days between each dose) for a total of 12 doses.

    Reporting group title
    ND-L02-s0201 45 mg
    Reporting group description
    		 ND-L02-s0201: 45 mg intravenous administration every 2 weeks (± 4 days for Visit 3 or ± 7 days for Visits 4 to 13, ensuring a minimum of 7 days between each dose) for a total of 12 doses.

    Reporting group title
    ND-L02-s0201 90 mg
    Reporting group description
    		 ND-L02-s0201: 90 mg intravenous administration every 2 weeks (± 4 days for Visit 3 or ± 7 days for Visits 4 to 13, ensuring a minimum of 7 days between each dose) for a total of 12 doses.

    Reporting group values
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg Total
    Number of subjects
    		 42 41 40 123
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 68.7 ( 6.16 ) 68.9 ( 6.22 ) 69.2 ( 6.53 ) -
    Gender categorical
    Units: Subjects
        Female
    		 5 7 6 18
        Male
    		 37 34 34 105
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0
        Asian
    		 7 10 7 24
        Black or African American
    		 0 2 1 3
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        White
    		 34 29 31 94
        Other
    		 1 0 1 2
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 5 2 4 11
        Not Hispanic/Latino
    		 37 39 36 112
        Unknown
    		 0 0 0 0
    Smoking History
    Units: Subjects
        Yes - not active smoker
    		 26 27 26 79
        No
    		 16 14 14 44
    Background Standard of Care
    Units: Subjects
        Nintedanib
    		 17 17 16 50
        Pirfenidone
    		 15 14 14 43
        None
    		 10 10 10 30
    Body mass index group
    Category ranges are in kg/m2.
    Units: Subjects
        Normal (18.5 - 24.9)
    		 12 11 10 33
        Overweight (25 - 29.9)
    		 15 17 22 54
        Obese (30 and above)
    		 15 13 8 36
    Eligibility Criteria Based on high-resolution computed tomography
    Participants were staged based on the presence or absence of a usual interstitial pneumonia (UIP) pattern on chest HRCT scans assessments. The diagnosis of IPF was confirmed by the PI using ATS/ERS/JRS/ALAT consensus criteria (Raghu et al, 2011: https://www.atsjournals.org/doi/full/10.1164/rccm.2009-040GL).
    Units: Subjects
        Definite UIP
    		 30 26 22 78
        Consistent with UIP
    		 6 10 11 27
        Possible UIP
    		 1 0 0 1
        Inconsistent with UIP
    		 5 5 7 17
    GAP IPF Stage
    The GAP IPF stage for each subject was calculated by adding up the points assigned to categories I, II, and III, where stage I is the better and stage III is the worst. gender (G); age (A); baseline FVC,% predicted; and baseline DLco, % predicted Stage I: 0 to 3 points. This stage has the lowest risk of mortality Stage II: 4 to 5 points. This stage has a moderate risk of mortality Stage III: 6 to 8 points. This stage has the highest risk of mortality
    Units: Subjects
        Stage I
    		 24 29 25 78
        Stage II
    		 17 11 15 43
        Stage III
    		 1 1 0 2
    Height
    Units: centimetre
        arithmetic mean (standard deviation)
    		 172.399 ( 6.5281 ) 172.316 ( 10.5278 ) 171.519 ( 9.2947 ) -
    Weight
    Units: kilogram(s)
        arithmetic mean (standard deviation)
    		 85.579 ( 15.4326 ) 84.234 ( 19.0174 ) 82.255 ( 17.6139 ) -
    Body mass index
    Units: kilogram(s)/square metre
        arithmetic mean (standard deviation)
    		 28.765 ( 4.7625 ) 28.093 ( 4.3072 ) 27.780 ( 4.5129 ) -
    Baseline Pulse Oximetry
    Percentage of oxygen saturated hemoglobin is presented
    Units: percentage
        arithmetic mean (standard deviation)
    		 96.5 ( 2.11 ) 96.6 ( 1.99 ) 96.9 ( 1.93 ) -
    Baseline Forced Vital Capacity
    Units: litres
        arithmetic mean (standard deviation)
    		 2.861 ( 0.7214 ) 3.012 ( 0.6866 ) 2.890 ( 0.7562 ) -
    Baseline Percent Predicted Forced Vital Capacity
    Percentage of total normal FVC is presented
    Units: percentage
        arithmetic mean (standard deviation)
    		 73.943 ( 17.0078 ) 79.319 ( 14.9940 ) 76.658 ( 18.1270 ) -
    Baseline Forced Expiratory Volume in 1 second
    Units: litres
        arithmetic mean (standard deviation)
    		 2.270 ( 0.5603 ) 2.380 ( 0.5345 ) 2.274 ( 0.5890 ) -
    Baseline Percent Predicted Forced Expiratory Volume in 1 second
    Percentage of normal FEV is presented.
    Units: percent
        arithmetic mean (standard deviation)
    		 76.890 ( 17.8868 ) 81.959 ( 14.8182 ) 78.766 ( 17.6653 ) -
    Baseline ratio of Forced Expiratory Volume in 1 second/Forced Vital Capacity
    Units: ratio
        arithmetic mean (standard deviation)
    		 0.795 ( 0.0501 ) 0.794 ( 0.0383 ) 0.787 ( 0.0450 ) -
    Baseline Diffusion Capacity of the Lung for Carbon Monoxide Corrected for Hemoglobin
    Units: mL/min/mmHg
        arithmetic mean (standard deviation)
    		 12.574 ( 3.9023 ) 12.972 ( 3.6453 ) 12.391 ( 3.3503 ) -
    Duration of idiopathic pulmonary fibrosis
    Units: months
        arithmetic mean (standard deviation)
    		 28.227 ( 17.4342 ) 24.678 ( 16.3543 ) 27.272 ( 15.7152 ) -
    Risk of Mortality at 1-year
    The risk of mortality (1-, 2-, and 3-year risk) was derived based on baseline data at the start of the treatment period using the Gender, Age, and Physiology (GAP) methodology. Risk of mortality was derived using the algorithm listed in SAP- Appendix 1: GAP Algorithm for IPF Stage and Predicted Mortality.
    Units: risk ratio
        arithmetic mean (standard deviation)
    		 14.726 ( 7.1570 ) 12.584 ( 4.9287 ) 13.930 ( 6.0984 ) -
    Risk of Mortality at 2-year
    The risk of mortality (1-, 2-, and 3-year risk) was derived based on baseline data at the start of the treatment period using the Gender, Age, and Physiology (GAP) methodology. Risk of mortality was derived using the algorithm listed in SAP- Appendix 1: GAP Algorithm for IPF Stage and Predicted Mortality.
    Units: risk ratio
        arithmetic mean (standard deviation)
    		 28.505 ( 12.5204 ) 24.922 ( 9.0103 ) 27.233 ( 11.0164 ) -
    Risk of Mortality at 3-year
    The risk of mortality (1-, 2-, and 3-year risk) was derived based on baseline data at the start of the treatment period using the Gender, Age, and Physiology (GAP) methodology. Risk of mortality was derived using the algorithm listed in SAP- Appendix 1: GAP Algorithm for IPF Stage and Predicted Mortality.
    Units: risk ratio
        arithmetic mean (standard deviation)
    		 40.335 ( 15.9727 ) 36.014 ( 11.9575 ) 38.869 ( 14.4372 ) -
    Baseline Hemoglobin Corrected percent predicted DLCO
    Units: percentage of normal DLCO
        arithmetic mean (standard deviation)
    		 51.762 ( 14.7970 ) 53.739 ( 13.1901 ) 51.914 ( 12.6957 ) -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Intravenous placebo infusion every 2 weeks (± 4 days for Visit 3 or ± 7 days for Visits 4 to 13, ensuring a minimum of 7 days between each dose) for a total of 12 doses.

    Reporting group title
    ND-L02-s0201 45 mg
    Reporting group description
    		 ND-L02-s0201: 45 mg intravenous administration every 2 weeks (± 4 days for Visit 3 or ± 7 days for Visits 4 to 13, ensuring a minimum of 7 days between each dose) for a total of 12 doses.

    Reporting group title
    ND-L02-s0201 90 mg
    Reporting group description
    		 ND-L02-s0201: 90 mg intravenous administration every 2 weeks (± 4 days for Visit 3 or ± 7 days for Visits 4 to 13, ensuring a minimum of 7 days between each dose) for a total of 12 doses.

    Primary: Number of participants discontinuing study treatment due to TEAEs

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    End point title
    		 Number of participants discontinuing study treatment due to TEAEs [1]
    End point description
    The number of participants with TEAEs leading to discontinuation from the study treatment. The Safety Population (including all participants who received at least one dose of study treatment) is presented. TEAE = treatment-emergent adverse event.
    End point type
    Primary
    End point timeframe
    Change in the incidence and severity of adverse events related to study treatment from baseline to 24 weeks
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis required for this endpoint.
    End point values
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Number of subjects analysed
    42
    41
    40
    Units: Participants
    1
    3
    4
    No statistical analyses for this end point

    Secondary: Rate of Decline in FVC from Baseline to Week 24

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    End point title
    		 Rate of Decline in FVC from Baseline to Week 24
    End point description
    Slope in FVC from Baseline to Week 24 (measured in L/week). The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. Slope and standard error are presented. The slope is approximated as least square mean/24 weeks. FVC = forced vital capacity
    End point type
    Secondary
    End point timeframe
    Baseline to Week 24
    End point values
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Number of subjects analysed
    42
    41
    40
    Units: litres
    arithmetic mean (standard error)
        Slope in FVC (L/week)
    -0.003366 ( 0.0014272 )
    -0.007519 ( 0.0015285 )
    -0.005478 ( 0.0015400 )
    Statistical analysis title
    		 Rate of Decline in FVC to Week 24: 45 mg v Placebo
    Statistical analysis description
    Slope in FVC (L/week) in the 45 mg cohort versus placebo
    Comparison groups
    Placebo v ND-L02-s0201 45 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.049
    Method
    		 random coefficient model
    Parameter type
    		 Slope Difference
    Point estimate
    -0.004153
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.008284
         upper limit
    		 -0.000021
    Statistical analysis title
    		 Rate of Decline in FVC to Week 24: 90 mg v Placebo
    Statistical analysis description
    Slope in FVC (L/week) in the 90 mg cohort versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.316
    Method
    		 random coefficient model
    Parameter type
    		 Slope Difference
    Point estimate
    -0.002112
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.00626
         upper limit
    		 0.002036

    Secondary: Absolute and Relative Change in FVC (L) from Baseline to Week 24

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    End point title
    		 Absolute and Relative Change in FVC (L) from Baseline to Week 24
    End point description
    Absolute and Relative Change in FVC (L) from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. FVC = forced vital capacity
    End point type
    Secondary
    End point timeframe
    Baseline to Week 24
    End point values
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Number of subjects analysed
    42
    41
    40
    Units: litres
    least squares mean (standard error)
        Baseline FVC (L)
    2.8754 ( 0.11079 )
    3.0242 ( 0.11207 )
    2.9032 ( 0.11328 )
        Week 24 FVC (L)
    2.7946 ( 0.10946 )
    2.8438 ( 0.11144 )
    2.7717 ( 0.11253 )
        Change from Baseline to Week 24 in FVC (L)
    -0.0808 ( 0.03425 )
    -0.1805 ( 0.03668 )
    -0.1315 ( 0.03696 )
    Statistical analysis title
    		 Change from Baseline to Week 24 in FVC (L): 45mg
    Statistical analysis description
    Change from Baseline to Week 24 in FVC (L) in the 45 mg cohort versus Placebo
    Comparison groups
    ND-L02-s0201 45 mg v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.049
    Method
    		 random coefficient model
    Parameter type
    		 Least Squares Mean Difference (Final)
    Point estimate
    -0.0997
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1988
         upper limit
    		 -0.0005
    Statistical analysis title
    		 Change from Baseline to Week 24 in FVC: 90 mg
    Statistical analysis description
    Change from Baseline to Week 24 in FVC (L) in the 90 mg cohort versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.316
    Method
    		 random coefficient model
    Parameter type
    		 Least Squares Mean Difference (Final)
    Point estimate
    -0.0507
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1502
         upper limit
    		 -0.0489

    Secondary: Summary of Study Treatment Response of FVC

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    End point title
    		 Summary of Study Treatment Response of FVC
    End point description
    Proportion of participants with an FVC response defined as either having improvement or a decline by 0 to less than or equal to 5%, more than 5% to less than or equal to 10%, and more than 10% at Visit 14 (Day 169). Participants with an FVC response were defined as improvement in FVC (ie, FVC value higher than baseline) or a decline of less than or equal to 10% from baseline. The intent-to-treat population (any randomised participants with treatment assignment according to the planned randomisation) is presented. FVC = forced vital capacity
    End point type
    Secondary
    End point timeframe
    Baseline to Visit 14 (Day 169)
    End point values
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Number of subjects analysed
    42
    41
    40
    Units: participants
        Improvement
    9
    7
    5
        Decline ≥0% to ≤5%
    10
    6
    10
        Decline >5% to ≤10%
    8
    6
    6
        Decline >10%
    3
    7
    4
        Test not done
    12
    15
    15
    No statistical analyses for this end point

    Secondary: Summary of Study Treatment Response of ppFVC

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    End point title
    		 Summary of Study Treatment Response of ppFVC
    End point description
    Proportion of participants with an ppFVC response defined as either having improvement or a decline by 0 to less than or equal to 5%, greater than 5% to less than or equal to 10%, and greater than 10% at Visit 14 (Day 169). Participants with a ppFVC response were defined as improvement in ppFVC (ie, ppFVC value higher than baseline) or a decline of less than or equal to 10% from baseline. The intent-to-treat population (any randomised participants with treatment assignment according to the planned randomisation) is presented. ppFVC = percent predicted forced vital capacity
    End point type
    Secondary
    End point timeframe
    Baseline to Visit 14 (Day 169)
    End point values
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Number of subjects analysed
    42
    41
    40
    Units: participants
        Improvement
    9
    7
    5
        Decline ≥0% to ≤5%
    10
    6
    10
        Decline >5% to ≤10%
    8
    6
    6
        Decline >10%
    3
    7
    4
        Test not done
    12
    15
    15
    No statistical analyses for this end point

    Secondary: Change in DLCO and DLCO corrected for hemoglobin from Baseline to Week 24

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    End point title
    		 Change in DLCO and DLCO corrected for hemoglobin from Baseline to Week 24
    End point description
    Change in diffusion capacity of the lung for carbon monoxide (DLCO) and DLCO corrected for hemoglobin (mL/min/mmHg) from Baseline to Week 24. The intent-to-treat population (any randomised participants with treatment assignment according to the planned randomisation) is presented.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 24
    End point values
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Number of subjects analysed
    42
    41
    40
    Units: mL/min/mmHg
    least squares mean (standard error)
        Baseline DLCO Corrected for Hemoglobin
    12.6709 ( 0.56489 )
    13.0723 ( 0.57141 )
    12.4800 ( 0.57759 )
        Week 24 DLCO Corrected for Hemoglobin
    11.7541 ( 0.58748 )
    12.3015 ( 0.59845 )
    12.2669 ( 0.60460 )
        Change from Baseline to Week 24 in DLCO Corrected
    -0.9169 ( 0.26950 )
    -0.7708 ( 0.28085 )
    -0.2131 ( 0.28408 )
        Baseline DLCO Not Corrected for Hemoglobin
    12.4411 ( 0.55897 )
    12.9860 ( 0.56543 )
    12.3792 ( 0.57155 )
        Week 24 DLCO Not Corrected for Hemoglobin
    11.5720 ( 0.57137 )
    12.2308 ( 0.58226 )
    12.0661 ( 0.58804 )
        Change from Baseline to Week 24 in DLCO Not Correc
    -0.8691 ( 0.26307 )
    -0.7551 ( 0.27406 )
    -0.3131 ( 0.27721 )
    Statistical analysis title
    		 DLCO Corrected: 45 mg cohort vs. Placebo
    Statistical analysis description
    Change from Baseline to Week 24 in DLCO Corrected for Hemoglobin (mL/min/mmHg) in the 45 mg cohort versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 45 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.708
    Method
    		 random coefficient
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.146
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6226
         upper limit
    		 0.9147
    Statistical analysis title
    		 DLCO Corrected: 90 mg cohort vs. Placebo
    Statistical analysis description
    Change from Baseline to Week 24 in DLCO Corrected for Hemoglobin (mL/min/mmHg) in the 90 mg cohort versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.074
    Method
    		 random coefficient
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.7038
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.0695
         upper limit
    		 1.4771
    Statistical analysis title
    		 DLCO Not Corrected: 45 mg cohort vs. Placebo
    Statistical analysis description
    Change from Baseline to Week 24 in DLCO Not Corrected for Hemoglobin (mL/min/mmHg) in the 45 mg cohort versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 45 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.765
    Method
    		 random coefficient
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.114
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.6362
         upper limit
    		 0.8641
    Statistical analysis title
    		 DLCO Not Corrected: 90 mg cohort vs. Placebo
    Statistical analysis description
    Change from Baseline to Week 24 in DLCO Not Corrected for Hemoglobin (mL/min/mmHg) in the 90 mg cohort versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.148
    Method
    		 random coefficient
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.556
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1986
         upper limit
    		 1.3107

    Secondary: Quantitative Changes of interstitial lung abnormalities as measured by HRCT

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    End point title
    		 Quantitative Changes of interstitial lung abnormalities as measured by HRCT
    End point description
    Changes of interstitial lung abnormalities as measured by high-resolution computed tomography (HRCT; ie, change in parenchymal feature [Baseline to Week 24), as determined by qualitative assessment (central radiologist) and quantitative analysis (Quantitative Lung Fibrosis – QLF analysis). Quantitative HRCT parameters included the following: • Quantitative Lung Fibrosis (QLF) score (% of whole lung field volume) • Ground glass opacity (GGO) (% of whole lung field volume) • Reticulation (% of whole lung field volume) • Honeycombing (% of whole lung field volume) • Normal lung (% of whole lung field volume) • Emphysema (low attenuation area [LAA]; % of whole lung field volume) The intent-to-treat population (any randomised participants with treatment assignment according to the planned randomisation) is presented.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 24
    End point values
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Number of subjects analysed
    42
    41
    40
    Units: percentage of whole lung field volume
    least squares mean (standard error)
        Baseline Ground Glass Opacity
    5.01 ( 0.357 )
    4.91 ( 0.399 )
    4.72 ( 0.367 )
        Week 24 Ground Glass Opacity
    4.77 ( 0.358 )
    4.49 ( 0.400 )
    4.52 ( 0.369 )
        Change Baseline to Week 24 Ground Glass Opacity
    -0.23 ( 0.177 )
    -0.41 ( 0.195 )
    -0.20 ( 0.182 )
        Baseline Reticulation
    27.46 ( 1.890 )
    23.69 ( 2.108 )
    24.03 ( 1.943 )
        Week 24 Reticulation
    28.13 ( 2.001 )
    24.97 ( 2.231 )
    26.34 ( 2.062 )
        Change from Baseline to Week 24 in Reticulation
    0.67 ( 0.964 )
    1.28 ( 1.069 )
    2.32 ( 1.010 )
        Baseline Honeycombing
    4.54 ( 0.861 )
    2.50 ( 0.961 )
    1.54 ( 0.886 )
        Week 24 Honeycombing
    6.36 ( 1.018 )
    3.11 ( 1.135 )
    2.37 ( 1.047 )
        Change from Baseline to Week 24 Honeycombing
    1.81 ( 0.542 )
    0.61 ( 0.604 )
    0.83 ( 0.558 )
        Baseline Normal Lung
    58.47 ( 2.281 )
    64.52 ( 2.544 )
    65.57 ( 2.343 )
        Week 24 Normal Lung
    56.42 ( 2.287 )
    63.35 ( 2.549 )
    62.68 ( 2.352 )
        Change from Baseline to Week 24 in Normal Lung
    -2.05 ( 1.027 )
    -1.17 ( 1.134 )
    -2.88 ( 1.057 )
        Baseline Emphysema
    9.62 ( 1.640 )
    10.66 ( 1.829 )
    8.14 ( 1.684 )
        Week 24 Emphysema
    12.08 ( 1.646 )
    9.54 ( 1.835 )
    8.45 ( 1.694 )
        Change from Baseline to Week 24 in Emphysema
    2.46 ( 0.936 )
    -1.12 ( 1.034 )
    0.31 ( 0.964 )
        Baseline QLF Score
    33.59 ( 2.189 )
    27.45 ( 2.441 )
    27.22 ( 2.249 )
        Week 24 QLF Score
    35.87 ( 2.195 )
    29.24 ( 2.447 )
    30.89 ( 2.258 )
        Change from Baseline to Week 24 in QLF Score
    2.28 ( 1.080 )
    1.79 ( 1.194 )
    3.67 ( 1.112 )
    Statistical analysis title
    		 Change from Baseline to Week 24 in QLF Score: 45mg
    Statistical analysis description
    Change from Baseline to Week 24 in QLF Score (% of whole lung field volume) in the 45 mg cohort versus Placebo
    Comparison groups
    ND-L02-s0201 45 mg v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.765
    Method
    		 random coefficient model
    Parameter type
    		 Least squares mean difference (final)
    Point estimate
    -0.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.68
         upper limit
    		 2.71
    Statistical analysis title
    		 Change from Baseline to Week 24 in QLF Score: 90mg
    Statistical analysis description
    Change from Baseline to Week 24 in QLF Score (% of whole lung field volume) in the 90 mg cohort versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.37
    Method
    		 random coefficient model
    Parameter type
    		 Least squares mean difference (final)
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.68
         upper limit
    		 4.47
    Statistical analysis title
    		 Change from Baseline to Week 24 in GGO: 45mg
    Statistical analysis description
    Change from Baseline to Week 24 in Ground Glass Opacity (% of whole lung field volume) in the 45 mg cohort versus Placebo. GGO = Ground Glass Opacity
    Comparison groups
    Placebo v ND-L02-s0201 45 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.499
    Method
    		 random coefficient model
    Parameter type
    		 Least squares mean difference (final)
    Point estimate
    -0.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 0.34
    Statistical analysis title
    		 Change from Baseline to Week 24 in GGO: 90mg
    Statistical analysis description
    Change from Baseline to Week 24 in Ground Glass Opacity (% of whole lung field volume) in the 90 mg cohort versus Placebo. GGO = Ground Glass Opacity
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.901
    Method
    		 random coefficient model
    Parameter type
    		 Least squares mean difference (final)
    Point estimate
    0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.47
         upper limit
    		 0.54
    Statistical analysis title
    		 Change from Baseline to Week 24 Reticulation: 45mg
    Statistical analysis description
    Change from Baseline to Week 24 in Reticulation (% of whole lung field volume) in the 45 mg cohort versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 45 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.676
    Method
    		 random coefficient model
    Parameter type
    		 Least squares mean difference (final)
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.25
         upper limit
    		 3.46
    Statistical analysis title
    		 Change from Baseline to Week 24 Reticulation: 90mg
    Statistical analysis description
    Change from Baseline to Week 24 in Reticulation (% of whole lung field volume) in the 90 mg cohort versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.242
    Method
    		 random coefficient model
    Parameter type
    		 Least squares mean difference (final)
    Point estimate
    1.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.13
         upper limit
    		 4.42
    Statistical analysis title
    		 Change Baseline to Week 24 Honeycombing: 45 mg
    Statistical analysis description
    Change from Baseline to Week 24 in Honeycombing (% of whole lung field volume) in the 45 mg cohort versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 45 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.14
    Method
    		 random coefficient model
    Parameter type
    		 Least squares mean difference (final)
    Point estimate
    -1.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.82
         upper limit
    		 0.4
    Statistical analysis title
    		 Change Baseline to Week 24 Honeycombing: 90mg
    Statistical analysis description
    Change from Baseline to Week 24 in Honeycombing (% of whole lung field volume) in the 90 mg cohort versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.211
    Method
    		 random coefficient model
    Parameter type
    		 Least squares mean difference (final)
    Point estimate
    -0.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.53
         upper limit
    		 0.56
    Statistical analysis title
    		 Change Baseline to Week 24 Normal Lung: 45 mg
    Statistical analysis description
    Change from Baseline to Week 24 in Normal Lung (% of whole lung field volume) in the 45 mg cohort versus Placebo
    Comparison groups
    ND-L02-s0201 45 mg v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.568
    Method
    		 random coefficient model
    Parameter type
    		 Least squares mean difference (final)
    Point estimate
    0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.16
         upper limit
    		 3.91
    Statistical analysis title
    		 Change Baseline to Week 24 Normal Lung: 90 mg
    Statistical analysis description
    Change from Baseline to Week 24 in Normal Lung (% of whole lung field volume) in the 90 mg cohort versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.573
    Method
    		 random coefficient model
    Parameter type
    		 Least squares mean difference (final)
    Point estimate
    -0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.76
         upper limit
    		 2.09
    Statistical analysis title
    		 Change Baseline to Week 24 in Emphysema: 45 mg
    Statistical analysis description
    Change from Baseline to Week 24 in Emphysema (% of whole lung field volume) in the 45 mg cohort versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 45 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.012
    Method
    		 random coefficient model
    Parameter type
    		 Least squares mean difference (final)
    Point estimate
    -3.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.35
         upper limit
    		 -0.81
    Statistical analysis title
    		 Change Baseline to Week 24 in Emphysema: 90 mg
    Statistical analysis description
    Change from Baseline to Week 24 in Emphysema (% of whole lung field volume) in the 90 mg cohort versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.112
    Method
    		 random coefficient model
    Parameter type
    		 Least squares mean difference (final)
    Point estimate
    -2.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.82
         upper limit
    		 0.51

    Secondary: Qualitative Changes of interstitial lung abnormalities as measured by HRCT

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    End point title
    		 Qualitative Changes of interstitial lung abnormalities as measured by HRCT
    End point description
    Changes of interstitial lung abnormalities as measured by high-resolution computed tomography (HRCT; ie, change in parenchymal feature [Baseline to Visit 14 (Day 169)]), as determined by qualitative assessment (central radiologist). The Likert scale values are included in the descriptions presented. The intent-to-treat population (any randomised participants with treatment assignment according to the planned randomisation) with HRCT assessment at Visit 14/Early Termination is presented.
    End point type
    Secondary
    End point timeframe
    Baseline to Visit 14 (Day 169)
    End point values
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Number of subjects analysed
    37
    30
    34
    Units: participants
        Much Better (5)
    0
    0
    0
        Better (4)
    0
    0
    1
        Same (3)
    28
    26
    28
        Worse (2)
    6
    3
    3
        Much Worse (1)
    3
    1
    2
        Unknown
    0
    0
    0
    Statistical analysis title
    		 ND-L02-s0201 45 mg versus Placebo
    Comparison groups
    ND-L02-s0201 45 mg v Placebo
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.256 [2]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [2] - p-value vs. Placebo
    Statistical analysis title
    		 ND-L02-s0201 90 mg versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    71
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.241 [3]
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval
    Notes
    [3] - p-value vs. Placebo

    Secondary: Events of IPF Exacerbation or Death and Rate of First IPF Exacerbation

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    End point title
    		 Events of IPF Exacerbation or Death and Rate of First IPF Exacerbation
    End point description
    Total number of events of participants who experienced idiopathic pulmonary fibrosis (IPF) exacerbation (ie, an unexplained worsening of dyspnea, evidence of hypoxemia as defined by worsened or severely impaired gas exchange, new radiographic alveolar infiltrates, and an absence of an alternative explanation such as infection, pulmonary embolism, pneumothorax, or heart failure) or death (weeks).
    End point type
    Secondary
    End point timeframe
    Baseline to study completion, up to Day 239
    End point values
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Number of subjects analysed
    42
    41
    40
    Units: events
    7
    3
    4
    Statistical analysis title
    		 Log-Rank Test 45mg vs. Placebo p-value
    Statistical analysis description
    Time to First IPF Exacerbation or Death (weeks) in the 45 mg cohort versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 45 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.517 [4]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.649
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.189
         upper limit
    		 2.225
    Notes
    [4] - The p-value was calculated using a log-rank test stratified by standard of care.
    Statistical analysis title
    		 Log-Rank Test 90mg vs. Placebo p-value
    Statistical analysis description
    Time to First IPF Exacerbation or Death (weeks) in the 90 mg cohort versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.506 [5]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.678
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.198
         upper limit
    		 2.324
    Notes
    [5] - The p-value was calculated using a log-rank test stratified by standard of care.
    Statistical analysis title
    		 Rate of First IPF Exacerbation (%): 45 mg
    Statistical analysis description
    Rate of First IPF Exacerbation (%) in the 45 mg cohort versus Placebo. The 95% CI for difference in proportions are based on the Chan-Zhang method.
    Comparison groups
    Placebo v ND-L02-s0201 45 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.313 [6]
    Method
    		 Fisher exact
    Parameter type
    		 Proportion Difference (Final Values)
    Point estimate
    -9.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25.2
         upper limit
    		 5.5
    Notes
    [6] - The p-value was based on Pearson's Chi-Square test. However, if any of the expected (not observed) cell counts are less than 5, a Fisher's Exact test was performed instead.
    Statistical analysis title
    		 Rate of First IPF Exacerbation (%): 90 mg
    Statistical analysis description
    Rate of First IPF Exacerbation (%) in the 90 mg cohort versus Placebo. The 95% CI for difference in proportions are based on the Chan-Zhang method.
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.376
    Method
    		 Chi-squared
    Parameter type
    		 Proportion Difference (Final Values)
    Point estimate
    -6.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.6
         upper limit
    		 9.2

    Secondary: Events of Hospitalization for Respiratory Ailments or Death

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    End point title
    		 Events of Hospitalization for Respiratory Ailments or Death
    End point description
    Events (participants who experienced hospitalization for respiratory ailments or died) for respiratory ailments are presented. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented.
    End point type
    Secondary
    End point timeframe
    Up to 12 weeks after the end of study treatment
    End point values
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Number of subjects analysed
    42
    41
    40
    Units: events
    5
    3
    3
    Statistical analysis title
    		 Rate of Hospitalization Respiratory Ailments: 45mg
    Statistical analysis description
    Rate of Hospitalization for Respiratory Ailments (%) in the 45 mg cohort versus Placebo. The 95% CI for difference in proportions are based on the Chan-Zhang method.
    Comparison groups
    Placebo v ND-L02-s0201 45 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.713
    Method
    		 Fisher exact
    Parameter type
    		 Proportion Difference (Final Values)
    Point estimate
    -4.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -19.2
         upper limit
    		 9.6
    Statistical analysis title
    		 Rate of Hospitalization Respiratory Ailments: 90mg
    Statistical analysis description
    Rate of Hospitalization for Respiratory Ailments (%) in the 90 mg cohort versus Placebo. The 95% CI for difference in proportions are based on the Chan-Zhang method.
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.713
    Method
    		 Fisher exact
    Parameter type
    		 Proportion Difference (Final Values)
    Point estimate
    -4.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -19.2
         upper limit
    		 10.7

    Secondary: Total Events of Death Due to All Causes

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    End point title
    		 Total Events of Death Due to All Causes
    End point description
    Rate of mortality due to all causes is presented. Overall survival was defined as the time from start of study treatment to death due to any cause.
    End point type
    Secondary
    End point timeframe
    Up to 12 weeks after the end of study treatment
    End point values
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Number of subjects analysed
    42
    41
    40
    Units: participants
    1
    1
    0
    Statistical analysis title
    		 Overall Survival (weeks) in the 45 mg cohort
    Statistical analysis description
    Overall Survival (weeks) in the 45 mg cohort versus Placebo
    Comparison groups
    ND-L02-s0201 45 mg v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.937
    Method
    		 Logrank
    Confidence interval
    Statistical analysis title
    		 Overall Survival (weeks) in the 90 mg cohort
    Statistical analysis description
    Overall Survival (weeks) in the 45 mg cohort versus Placebo
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.414
    Method
    		 Logrank
    Confidence interval
    Statistical analysis title
    		 Rate of Mortality (%) in the 45 mg cohort
    Statistical analysis description
    Rate of Mortality (%) in the 45 mg cohort versus Placebo. The 95% CI for difference in proportions are based on the Chan-Zhang method.
    Comparison groups
    Placebo v ND-L02-s0201 45 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.999
    Method
    		 Fisher exact
    Parameter type
    		 Proportion Difference (Final Values)
    Point estimate
    0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.4
         upper limit
    		 10.9
    Statistical analysis title
    		 Rate of Mortality (%) in the 90 mg cohort
    Statistical analysis description
    Rate of Mortality (%) in the 90 mg cohort versus Placebo. The 95% CI for difference in proportions are based on the Chan-Zhang method.
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.999
    Method
    		 Fisher exact
    Parameter type
    		 Proportion Difference (Final Values)
    Point estimate
    -2.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -13.1
         upper limit
    		 6.8

    Secondary: Events of Deterioration of IPF Resulting in Lung Transplantation or Death and Rate of Deterioration of IPF Resulting in Lung Transplantation

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    End point title
    		 Events of Deterioration of IPF Resulting in Lung Transplantation or Death and Rate of Deterioration of IPF Resulting in Lung Transplantation
    End point description
    Events of deterioration of Idiopathic Pulmonary Fibrosis (IPF) resulting in lung transplantation (LP; up to 12 weeks after the end of study treatment) or death (weeks) and rate of deterioration of IPF resulting in lung transplantation (up to 12 weeks after the end of study treatment) are presented. Total events = Participants who experience deterioration of IPF resulting in LP (or died). Rate of Deterioration = Rate of Deterioration of IPF Resulting in LP.
    End point type
    Secondary
    End point timeframe
    Baseline to 12 weeks after end of study treatment
    End point values
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Number of subjects analysed
    42
    41
    40
    Units: events
        Total events
    3
    1
    0
        Rate of Deterioration
    2
    0
    0
    Statistical analysis title
    		 Rate of Deterioration of IPF: 45 mg vs. Placebo
    Statistical analysis description
    Rate of Deterioration of IPF Resulting in Lung Transplantation (%) in the 45 mg cohort versus Placebo. The 95% CI for difference in proportions are based on the Chan-Zhang method.
    Comparison groups
    Placebo v ND-L02-s0201 45 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.494
    Method
    		 Fisher exact
    Parameter type
    		 Proportion Difference (Final Values)
    Point estimate
    -4.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.6
         upper limit
    		 4.6
    Statistical analysis title
    		 Rate of Deterioration of IPF: 90 mg vs. Placebo
    Statistical analysis description
    Rate of Deterioration of IPF Resulting in Lung Transplantation (%) in the 90 mg cohort versus Placebo. The 95% CI for difference in proportions are based on the Chan-Zhang method.
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.494
    Method
    		 Fisher exact
    Parameter type
    		 Proportion Difference (Final Values)
    Point estimate
    -4.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.2
         upper limit
    		 4.5

    Secondary: Rate of Decline in ppFVC from Baseline to Week 24

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    End point title
    		 Rate of Decline in ppFVC from Baseline to Week 24
    End point description
    Slope in ppFVC from Baseline to Week 24 (measured in %/week). The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. Slope and standard error are presented. The slope is approximated as least square mean/24 weeks. ppFVC = percent predicted forced vital capacity
    End point type
    Secondary
    End point timeframe
    Baseline to Week 24
    End point values
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Number of subjects analysed
    42
    41
    40
    Units: %/week
        arithmetic mean (standard error)
    -0.096455 ( 0.0373658 )
    -0.187694 ( 0.0400588 )
    -0.136051 ( 0.0403636 )
    Statistical analysis title
    		 Rate of Decline in ppFVC: 45 mg versus placebo
    Comparison groups
    Placebo v ND-L02-s0201 45 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.098
    Method
    		 random coefficient model
    Parameter type
    		 Slope
    Point estimate
    -0.091238
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.199456
         upper limit
    		 0.016979
    Statistical analysis title
    		 Rate of Decline in ppFVC: 90 mg versus placebo
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.473
    Method
    		 random coefficient model
    Parameter type
    		 Slope
    Point estimate
    -0.039596
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.148248
         upper limit
    		 0.069056

    Secondary: Percent Change in FVC From Baseline to Week 24

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    End point title
    		 Percent Change in FVC From Baseline to Week 24
    End point description
    Percent Change in FVC from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. FVC = forced vital capacity
    End point type
    Secondary
    End point timeframe
    Baseline to Week 24
    End point values
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Number of subjects analysed
    42
    41
    40
    Units: percent
        least squares mean (standard error)
    -3.10 ( 4.793 )
    -5.64 ( 4.488 )
    -4.23 ( 4.723 )
    Statistical analysis title
    		 Placebo versus ND-L02-s0201 45 mg
    Comparison groups
    Placebo v ND-L02-s0201 45 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.668
    Method
    		 random coefficient model
    Parameter type
    		 Median difference (final values)
    Point estimate
    -3.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.59
         upper limit
    		 11.28
    Statistical analysis title
    		 Placebo versus ND-L02-s0201 90 mg
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.821
    Method
    		 random coefficient model
    Parameter type
    		 Median difference (final values)
    Point estimate
    -1.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.57
         upper limit
    		 13.13

    Secondary: Absolute and Relative Change in ppFVC (%) From Baseline to Week 24

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    End point title
    		 Absolute and Relative Change in ppFVC (%) From Baseline to Week 24
    End point description
    Absolute and Relative Change in ppFVC (%) from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. ppFVC = percent predicted forced vital capacity
    End point type
    Secondary
    End point timeframe
    Baseline to Week 24
    End point values
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Number of subjects analysed
    42
    41
    40
    Units: percent
    least squares mean (standard error)
        Baseline ppFVC
    74.5701 ( 2.54894 )
    79.8896 ( 2.57837 )
    77.2260 ( 2.60623 )
        Week 24 ppFVC
    72.2552 ( 2.58376 )
    75.3849 ( 2.63382 )
    73.9607 ( 2.65995 )
        Change from Baseline to Week 24 in ppFVC
    -2.3149 ( 0.89678 )
    -4.5046 ( 0.96141 )
    -3.2652 ( 0.96873 )
    Statistical analysis title
    		 Change from baseline to Week 24 in ppFVC: 45 mg
    Comparison groups
    Placebo v ND-L02-s0201 45 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.098
    Method
    		 random coefficient model
    Parameter type
    		 Median difference (final values)
    Point estimate
    -2.1897
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.7869
         upper limit
    		 0.4075
    Statistical analysis title
    		 Change from Baseline to Week 24 in ppFVC: 90 mg
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.473
    Method
    		 random coefficient model
    Parameter type
    		 Median difference (final values)
    Point estimate
    -0.9503
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.5579
         upper limit
    		 1.6573

    Secondary: Percent Change in ppFVC From Baseline to Week 24

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    End point title
    		 Percent Change in ppFVC From Baseline to Week 24
    End point description
    Percent Change in ppFVC from Baseline to Week 24. The intent-to-treat population (any randomized participants with treatment assignment according to the planned randomization) is presented. ppFVC = percent predicted forced vital capacity
    End point type
    Secondary
    End point timeframe
    Baseline to Week 24
    End point values
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Number of subjects analysed
    42
    41
    40
    Units: percent
        least squares mean (standard error)
    -3.10 ( 4.793 )
    -5.64 ( 4.488 )
    -4.23 ( 4.723 )
    Statistical analysis title
    		 Percent Change in ppFVC: 45mg versus placebo
    Comparison groups
    Placebo v ND-L02-s0201 45 mg
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7
    Method
    		 random coefficient model
    Parameter type
    		 Median difference (final values)
    Point estimate
    -2.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -15.4
         upper limit
    		 10.34
    Statistical analysis title
    		 Percent Change in ppFVC: 90mg versus placebo
    Comparison groups
    Placebo v ND-L02-s0201 90 mg
    Number of subjects included in analysis
    82
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.867
    Method
    		 random coefficient model
    Parameter type
    		 Median difference (final values)
    Point estimate
    -1.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.31
         upper limit
    		 12.07

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Approximately 40 weeks (from screening to follow-up visit).
    Adverse event reporting additional description
    The safety population includes all participants who received at least one dose of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Intravenous placebo infusion every 2 weeks (± 4 days for Visit 3 or ± 7 days for Visits 4 to 13, ensuring a minimum of 7 days between each dose) for a total of 12 doses.

    Reporting group title
    ND-L02-s0201 45 mg
    Reporting group description
    		 ND-L02-s0201: 45 mg intravenous administration every 2 weeks (± 4 days for Visit 3 or ± 7 days for Visits 4 to 13, ensuring a minimum of 7 days between each dose) for a total of 12 doses.

    Reporting group title
    ND-L02-s0201 90 mg
    Reporting group description
    		 ND-L02-s0201: 90 mg intravenous administration every 2 weeks (± 4 days for Visit 3 or ± 7 days for Visits 4 to 13, ensuring a minimum of 7 days between each dose) for a total of 12 doses.

    Serious adverse events
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 42 (21.43%)
    4 / 41 (9.76%)
    6 / 40 (15.00%)
         number of deaths (all causes)
    1
    1
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 41 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 41 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Anastomotic haemorrhage
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 41 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 41 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cervical radiculopathy
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 41 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 41 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thalamic infarction
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 41 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Vascular stent stenosis
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 41 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diverticulum
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 41 (2.44%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Idiopathic pulmonary fibrosis
         subjects affected / exposed
    4 / 42 (9.52%)
    0 / 41 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 41 (2.44%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 41 (2.44%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Influenza
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 41 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 41 (2.44%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 41 (2.44%)
    1 / 40 (2.50%)
         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
    		 Placebo ND-L02-s0201 45 mg ND-L02-s0201 90 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    35 / 42 (83.33%)
    37 / 41 (90.24%)
    37 / 40 (92.50%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 41 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    2
    General disorders and administration site conditions
    Chest discomfort
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 41 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    0
    0
    3
    Fatigue
         subjects affected / exposed
    3 / 42 (7.14%)
    3 / 41 (7.32%)
    5 / 40 (12.50%)
         occurrences all number
    3
    3
    5
    Infusion site reaction
         subjects affected / exposed
    1 / 42 (2.38%)
    6 / 41 (14.63%)
    2 / 40 (5.00%)
         occurrences all number
    1
    6
    3
    Oedema peripheral
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 41 (2.44%)
    2 / 40 (5.00%)
         occurrences all number
    1
    1
    2
    Pain
         subjects affected / exposed
    2 / 42 (4.76%)
    0 / 41 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    2
    0
    0
    Pyrexia
         subjects affected / exposed
    2 / 42 (4.76%)
    0 / 41 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    2
    0
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    9 / 42 (21.43%)
    4 / 41 (9.76%)
    6 / 40 (15.00%)
         occurrences all number
    12
    4
    7
    Dyspnoea
         subjects affected / exposed
    5 / 42 (11.90%)
    4 / 41 (9.76%)
    3 / 40 (7.50%)
         occurrences all number
    7
    4
    3
    Hypoxia
         subjects affected / exposed
    4 / 42 (9.52%)
    0 / 41 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    6
    0
    0
    Idiopathic pulmonary fibrosis
         subjects affected / exposed
    4 / 42 (9.52%)
    3 / 41 (7.32%)
    4 / 40 (10.00%)
         occurrences all number
    5
    3
    4
    Rhinorrhoea
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 41 (2.44%)
    2 / 40 (5.00%)
         occurrences all number
    0
    1
    2
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 41 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    1
    0
    3
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 41 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 41 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    2
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 41 (2.44%)
    3 / 40 (7.50%)
         occurrences all number
    0
    1
    3
    Lipase increased
         subjects affected / exposed
    0 / 42 (0.00%)
    2 / 41 (4.88%)
    1 / 40 (2.50%)
         occurrences all number
    0
    2
    1
    Weight decreased
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 41 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    2
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 42 (0.00%)
    2 / 41 (4.88%)
    0 / 40 (0.00%)
         occurrences all number
    0
    2
    0
    Fall
         subjects affected / exposed
    3 / 42 (7.14%)
    0 / 41 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    4
    0
    0
    Infusion related reaction
         subjects affected / exposed
    3 / 42 (7.14%)
    14 / 41 (34.15%)
    19 / 40 (47.50%)
         occurrences all number
    4
    46
    56
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    2 / 42 (4.76%)
    1 / 41 (2.44%)
    0 / 40 (0.00%)
         occurrences all number
    2
    1
    0
    Headache
         subjects affected / exposed
    3 / 42 (7.14%)
    4 / 41 (9.76%)
    3 / 40 (7.50%)
         occurrences all number
    3
    7
    3
    Hypoaesthesia
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 41 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    1
    0
    2
    Presyncope
         subjects affected / exposed
    1 / 42 (2.38%)
    0 / 41 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    1
    0
    2
    Eye disorders
    Vision blurred
         subjects affected / exposed
    0 / 42 (0.00%)
    2 / 41 (4.88%)
    0 / 40 (0.00%)
         occurrences all number
    0
    2
    0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 42 (2.38%)
    1 / 41 (2.44%)
    2 / 40 (5.00%)
         occurrences all number
    1
    1
    2
    Diarrhoea
         subjects affected / exposed
    2 / 42 (4.76%)
    2 / 41 (4.88%)
    1 / 40 (2.50%)
         occurrences all number
    5
    2
    2
    Nausea
         subjects affected / exposed
    2 / 42 (4.76%)
    4 / 41 (9.76%)
    2 / 40 (5.00%)
         occurrences all number
    2
    4
    2
    Vomiting
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 41 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    2
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    1 / 42 (2.38%)
    3 / 41 (7.32%)
    1 / 40 (2.50%)
         occurrences all number
    1
    3
    1
    Rash
         subjects affected / exposed
    2 / 42 (4.76%)
    1 / 41 (2.44%)
    3 / 40 (7.50%)
         occurrences all number
    2
    1
    5
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 42 (4.76%)
    1 / 41 (2.44%)
    2 / 40 (5.00%)
         occurrences all number
    3
    1
    2
    Back pain
         subjects affected / exposed
    5 / 42 (11.90%)
    3 / 41 (7.32%)
    3 / 40 (7.50%)
         occurrences all number
    5
    3
    3
    Muscle spasms
         subjects affected / exposed
    2 / 42 (4.76%)
    0 / 41 (0.00%)
    0 / 40 (0.00%)
         occurrences all number
    2
    0
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 42 (0.00%)
    1 / 41 (2.44%)
    2 / 40 (5.00%)
         occurrences all number
    0
    1
    2
    COVID-19
         subjects affected / exposed
    2 / 42 (4.76%)
    1 / 41 (2.44%)
    3 / 40 (7.50%)
         occurrences all number
    2
    1
    3
    Gastroenteritis
         subjects affected / exposed
    0 / 42 (0.00%)
    0 / 41 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    2
    Nasopharyngitis
         subjects affected / exposed
    0 / 42 (0.00%)
    3 / 41 (7.32%)
    1 / 40 (2.50%)
         occurrences all number
    0
    3
    1
    Sinusitis
         subjects affected / exposed
    2 / 42 (4.76%)
    0 / 41 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    2
    0
    2
    Upper respiratory tract infection
         subjects affected / exposed
    5 / 42 (11.90%)
    2 / 41 (4.88%)
    2 / 40 (5.00%)
         occurrences all number
    5
    2
    2
    Urinary tract infection
         subjects affected / exposed
    2 / 42 (4.76%)
    1 / 41 (2.44%)
    0 / 40 (0.00%)
         occurrences all number
    3
    2
    0
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    0 / 42 (0.00%)
    2 / 41 (4.88%)
    0 / 40 (0.00%)
         occurrences all number
    0
    2
    0
    Hyponatraemia
         subjects affected / exposed
    2 / 42 (4.76%)
    1 / 41 (2.44%)
    0 / 40 (0.00%)
         occurrences all number
    2
    1
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Mar 2018
    Global Amendment: A combination toxicity study was completed in rats with ND-L02-s0201 and nintedanib. • The risk language was updated to include results from this study. Changes were incorporated based on feedback from the Sponsor and clinical team. • Updated exclusion criterion #12 to remove “full-dose anticoagulant therapy or high-dose antiplatelet therapy.” • Clarified that the GAP staging assessment was a calculated factor that would be performed by the statistician. • Clarified the timing of the ECG collection at Visits 4 and 8. • Clarified that if a historical HRCT was available, it was to be submitted for overread to determine preliminary eligibility prior to the subject’s Visit 1b HRCT. • Clarified that all subjects that met preliminary eligibility criteria were to have an HRCT scan at Visit 1b. • Added guidance for study staff on how to manage unblinding if a subject experienced an IRR. • Added RR to the list of ECG intervals. • Clarified that grading of AE severity was to use NCI CTCAE v5.0.
    08 Jul 2019
    Global Amendment: Updated based on comments received from FDA on 14 March 2018 and 20 April 2018. • Allowing dose adjustments or discontinuation of standard care as needed. • Allowing patients to start standard care after completing another treatment. • Adding ADA samples at Days 15 and 29. • Collecting a tryptase blood sample at the beginning. • Only allowing withdrawal if a subject withdraws consent. • Clarifying study withdrawal and data prevention steps. • Banking remaining ADA test samples. • Monitoring subjects with positive ADA until titers return to baseline.
    18 Sep 2019
    Global Amendment: Aligned the frequency of pregnancy tests with the CTFG guidelines and updated the protocol with respect to several minor issues. • Added urine pregnancy tests to Visits 4, 8, 12, and 15 (Days 29, 85, 141, and 197). • During treatment, pregnancy tests were performed every 4 weeks. After treatment, pregnancy tests were performed 2, 6, and 12 weeks after the last infusion. • Clarified when a second HRCT was required in the event of a rescreen. • Expanded the list of public clinical trial databases to include the US, Europe, and Japan.
    17 Jun 2020
    Global Amendment: Provided guidance to investigators regarding clinical trial conduct during outbreaks/pandemics resulting from SARS-CoV-2 infections. The guidance is based safety measures taken due to the COVID-19 pandemic. • Added cross references to Appendix F (Section 18.6) where guidance on clinical trial conduct relating COVID-19 was presented. • Clarified that the sample size of 40 subjects per treatment arm was approximate. • Added exclusion criterion for SARS-CoV-2 positive test. • Stated that additional sensitivity analyses were to be performed due to the COVID-19 pandemic in accordance with regulatory guidelines. • Stated that an HRCT was not required for subjects who terminated the study early and received <5 doses. • Stated that if a subject had an HRCT scan performed due to medical indication, the Investigator should consider whether to include it as an unscheduled scan or as the Visit 14/ET scan. • Changed the timing of the second and third scheduled DMC meetings to: o After 50% of subjects completed Visit 4 (Day 29) o After 75% of subjects completed Visit 8 (Day 85) • Indicated that subjects whose participation in the study was affected by restrictions relating to COVID-19, may be replaced. • Included guidance on how to conduct remote monitoring in accordance with the remote monitoring plan if onsite monitoring was not possible. • Added an appendix that provides guidelines for investigators for how to deal with restrictions relating to COVID-19.

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

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