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    Clinical Trial Results:
    A Phase 3 Randomized, Double-Blind, Multi-Dose, Placebo and NSAID-Controlled Study to Evaluate The Efficacy and Safety of Fasinumab in Patients With Pain Due to Osteoarthritis of The Knee or Hip

    Summary
    EudraCT number
    2017-001702-15
    Trial protocol
    DK   DE   EE   GB   RO  
    Global end of trial date
    09 Nov 2020

    Results information
    Results version number
    v1(current)
    This version publication date
    24 Nov 2021
    First version publication date
    24 Nov 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    R475-OA-1688
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03304379
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Regeneron Pharmaceuticals, Inc.
    Sponsor organisation address
    777 Old Saw Mill River Rd., Tarrytown, United States, 10591
    Public contact
    Clinical Trial Administrator, Regeneron Pharmaceuticals, Inc., 001 844-734-6643, clinicaltrials@regeneron.com
    Scientific contact
    Clinical Trial Administrator, Regeneron Pharmaceuticals, Inc., 001 844-734-6643, clinicaltrials@regeneron.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
    09 Nov 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Nov 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this study was to evaluate the efficacy of Fasinumab compared to placebo and non-steroidal anti-inflammatory drug (NSAIDs) when administered for up to 24 weeks in subjects with pain due to osteoarthritis (OA) of the knee or hip.
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the International Conference on Harmonisation (ICH) guidelines for Good Clinical Practice (GCP) and applicable regulatory requirements.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    26 Oct 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 737
    Country: Number of subjects enrolled
    Canada: 17
    Country: Number of subjects enrolled
    Estonia: 17
    Country: Number of subjects enrolled
    Germany: 92
    Country: Number of subjects enrolled
    Poland: 331
    Country: Number of subjects enrolled
    South Africa: 329
    Country: Number of subjects enrolled
    Romania: 54
    Country: Number of subjects enrolled
    United Kingdom: 73
    Worldwide total number of subjects
    1650
    EEA total number of subjects
    494
    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)
    1005
    From 65 to 84 years
    637
    85 years and over
    8

    Subject disposition

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    Recruitment
    Recruitment details
    A total of 4531 subjects were screened, of which 1650 subjects were randomised.

    Pre-assignment
    Screening details
    The study consisted of a screening period of up to 30 days, a 7-10-day pre-randomisation/washout period (7 days +3 day window), a 24-week treatment period (with last Q4W dose of study drug administered at week 20), a 20-week follow-up period, and a final phone call approximately 52 weeks after the last subcutaneous (SC) dose of study drug.

    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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Subjects who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo matched to NSAIDs
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received oral dose of placebo matched to NSAID BID up to 24 weeks.

    Investigational medicinal product name
    Placebo matched to Fasinumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received SC injections of placebo matched to Fasinumab in the abdomen, thigh or upper arm up to 24 weeks.

    Arm title
    NSAIDs
    Arm description
    Subjects received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Diclofenac
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 75 mg of Diclofenac BID up to 24 weeks.

    Investigational medicinal product name
    Celecoxib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects received 200 mg of Celecoxib QD up to 24 weeks.

    Arm title
    Fasinumab 1 mg
    Arm description
    Subjects received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
    Arm type
    Experimental

    Investigational medicinal product name
    Fasinumab
    Investigational medicinal product code
    REGN475
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks.

    Arm title
    Fasinumab 3 mg
    Arm description
    Subjects received SC injection of Fasinumab at a dose of 3 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID
    Arm type
    Experimental

    Investigational medicinal product name
    Fasinumab
    Investigational medicinal product code
    REGN475
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received SC injection of Fasinumab at a dose of 3 mg Q4W up to 24 weeks.

    Arm title
    Fasinumab 6 mg
    Arm description
    Subjects received SC injection of Fasinumab at a dose of 6 mg Q8W up to 24 weeks, alternating with Q8W placebo injections. Subjects received placebo injections at the Q4W study visits where study drug was not administered and NSAID-matching placebo oral, BID
    Arm type
    Experimental

    Investigational medicinal product name
    Fasinumab
    Investigational medicinal product code
    REGN475
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received SC injection of Fasinumab at a dose of 6 mg Q8W up to 24 weeks.

    Number of subjects in period 1
    Placebo NSAIDs Fasinumab 1 mg Fasinumab 3 mg Fasinumab 6 mg
    Started
    308
    612
    612
    59
    59
    Completed
    238
    471
    463
    42
    42
    Not completed
    70
    141
    149
    17
    17
         Other Unspecified
    -
    1
    -
    -
    -
         Death
    1
    2
    -
    -
    -
         Protocol deviation
    8
    10
    5
    -
    2
         Physician decision
    6
    10
    6
    9
    10
         Lack of efficacy
    17
    16
    20
    -
    -
         Adverse event, non-fatal
    4
    20
    17
    1
    -
         Consent withdrawn by subject
    26
    58
    66
    3
    5
         Lost to follow-up
    8
    24
    35
    4
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Subjects who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.

    Reporting group title
    NSAIDs
    Reporting group description
    Subjects received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks.

    Reporting group title
    Fasinumab 1 mg
    Reporting group description
    Subjects received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID

    Reporting group title
    Fasinumab 3 mg
    Reporting group description
    Subjects received SC injection of Fasinumab at a dose of 3 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID

    Reporting group title
    Fasinumab 6 mg
    Reporting group description
    Subjects received SC injection of Fasinumab at a dose of 6 mg Q8W up to 24 weeks, alternating with Q8W placebo injections. Subjects received placebo injections at the Q4W study visits where study drug was not administered and NSAID-matching placebo oral, BID

    Reporting group values
    Placebo NSAIDs Fasinumab 1 mg Fasinumab 3 mg Fasinumab 6 mg Total
    Number of subjects
    308 612 612 59 59 1650
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    62.0 ± 9.30 62.3 ± 9.41 62.1 ± 9.13 62.8 ± 9.38 61.5 ± 9.55 -
    Gender categorical
    Units: Subjects
        Female
    222 418 436 36 34 1146
        Male
    86 194 176 23 25 504
    Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score
    WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in the past 48 hours. It was calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (higher pain), where higher scores indicated higher pain.
    Units: Score on a Scale
        arithmetic mean (standard deviation)
    6.4 ± 1.39 6.4 ± 1.34 6.5 ± 1.32 6.4 ± 1.40 6.5 ± 1.28 -
    WOMAC Physical Function Subscale Scores
    WOMAC physical function subscale:17-item questionnaire used to assess degree of difficulty experienced due to OA in index joint during past 48 hours. It was calculated as mean of scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated maximum difficulty.
    Units: Score on a Scale
        arithmetic mean (standard deviation)
    6.40 ± 1.495 6.32 ± 1.418 6.39 ± 1.462 6.50 ± 1.350 6.34 ± 1.392 -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Subjects who received subcutaneous (SC) injection of placebo matched to Fasinumab every 4 weeks (Q4W) or every 8 weeks (Q8W) alternatively or oral placebo matched to NSAID twice daily (BID) up to 24 weeks.

    Reporting group title
    NSAIDs
    Reporting group description
    Subjects received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks.

    Reporting group title
    Fasinumab 1 mg
    Reporting group description
    Subjects received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID

    Reporting group title
    Fasinumab 3 mg
    Reporting group description
    Subjects received SC injection of Fasinumab at a dose of 3 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID

    Reporting group title
    Fasinumab 6 mg
    Reporting group description
    Subjects received SC injection of Fasinumab at a dose of 6 mg Q8W up to 24 weeks, alternating with Q8W placebo injections. Subjects received placebo injections at the Q4W study visits where study drug was not administered and NSAID-matching placebo oral, BID

    Primary: Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Scores up to Week 24 in Subjects Treated With Fasinumab Compared to Placebo

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    End point title
    Change From Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Scores up to Week 24 in Subjects Treated With Fasinumab Compared to Placebo [1]
    End point description
    WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in past 48 hours. It was calculated as the mean of the scores from the 5 individual questions scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (higher pain), where higher scores indicated higher pain. Here, “Number of Subjects Analysed” signifies those subjects who were evaluable for this endpoint. The modified full analysis set (mFAS) includes all randomized subjects in the FAS but excludes subjects from four sites for which there were potential concerns regarding data quality, identified prior to database lock.
    End point type
    Primary
    End point timeframe
    Baseline up to Week 24
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only fasinumab 1 mg and placebo were evaluated in this endpoint. The fasinumab 3 mg and 6 mg arms were not evaluated as they were discontinued early in the study.
    End point values
    Placebo Fasinumab 1 mg
    Number of subjects analysed
    208
    439
    Units: Score on a Scale
    least squares mean (standard error)
        FAS (n=208, 439)
    -2.21 ± 0.165
    -2.84 ± 0.127
        mFAS (n=173, 372)
    -2.01 ± 0.182
    -2.78 ± 0.141
    Statistical analysis title
    Pooled Placebo vs Fasinumab 1 mg
    Statistical analysis description
    Analyses were based on a multiple imputation approach using an Mixed-Effect Model With Repeated Measure (MMRM) model with baseline randomization strata, baseline, treatment, visit and treatment by-visit interaction.
    Comparison groups
    Placebo v Fasinumab 1 mg
    Number of subjects included in analysis
    647
    Analysis specification
    Pre-specified
    Analysis type
    superiority [2]
    P-value
    = 0.0003 [3]
    Method
    MMRM
    Parameter type
    Least Square (LS) Mean Difference
    Point estimate
    -0.63
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.971
         upper limit
    -0.286
    Notes
    [2] - FAS
    [3] - Threshold for significance at 0.05 level.
    Statistical analysis title
    Pooled Placebo vs Fasinumab 1 mg (mFAS)
    Statistical analysis description
    Analyses were based on a multiple imputation approach using a MMRM model with baseline, randomization strata, baseline, treatment, visit and treatment by-visit interaction
    Comparison groups
    Placebo v Fasinumab 1 mg
    Number of subjects included in analysis
    647
    Analysis specification
    Pre-specified
    Analysis type
    superiority [4]
    P-value
    > 0.0001 [5]
    Method
    MMRM
    Parameter type
    Least Square (LS) Mean Difference
    Point estimate
    -0.77
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.154
         upper limit
    -0.383
    Notes
    [4] - Subjects in mFAS analysis = 545
    [5] - Threshold for significance at 0.05 level.

    Primary: Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Subjects Treated With Fasinumab Compared to Placebo

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    End point title
    Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Subjects Treated With Fasinumab Compared to Placebo [6]
    End point description
    Physical function referred to subject's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale was a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated maximum difficulty. Here, “Number of Subjects Analysed” signifies those subjects who were evaluable for this endpoint. The modified full analysis set (mFAS) includes all randomized subjects in the FAS but excludes subjects from four sites for which there were potential concerns regarding data quality, identified prior to database lock.
    End point type
    Primary
    End point timeframe
    Baseline up to Week 24
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The fasinumab 3 mg and 6 mg arms were not evaluated as they were discontinued early in the study.
    End point values
    Placebo Fasinumab 1 mg
    Number of subjects analysed
    207
    439
    Units: Score on a Scale
    least squares mean (standard error)
        FAS (n=208, 439)
    -2.02 ± 0.164
    -2.65 ± 0.125
        mFAS (n=173, 372)
    -1.80 ± 0.180
    -2.62 ± 0.138
    Statistical analysis title
    Pooled Placebo vs Fasinumab 1 mg
    Statistical analysis description
    Analyses were based on a multiple imputation approach using an Mixed-Effect Model With Repeated Measure (MMRM) model with baseline randomization strata, baseline, treatment, visit and treatment by-visit interaction.
    Comparison groups
    Placebo v Fasinumab 1 mg
    Number of subjects included in analysis
    646
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0003 [7]
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    -0.64
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.981
         upper limit
    -0.29
    Notes
    [7] - Threshold for significance at 0.05 level.
    Statistical analysis title
    Pooled Placebo vs Fasinumab 1 mg (mFAS)
    Statistical analysis description
    Analyses were based on a multiple imputation approach using an Mixed-Effect Model With Repeated Measure (MMRM) model with baseline randomization strata, baseline, treatment, visit and treatment by-visit interaction.
    Comparison groups
    Placebo v Fasinumab 1 mg
    Number of subjects included in analysis
    646
    Analysis specification
    Pre-specified
    Analysis type
    superiority [8]
    P-value
    < 0.0001 [9]
    Method
    MMRM
    Parameter type
    Least Square (LS) Mean Difference
    Point estimate
    -0.82
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.198
         upper limit
    -0.443
    Notes
    [8] - Subjects in mFAS analysis = 545
    [9] - Threshold for significance at 0.05 level

    Secondary: Percentage of Subjects With Greater Than or Equal to (≥) 30 Percent (%) Reduction From Baseline up to Week 24 in WOMAC Pain Subscale Score in Subjects Treated With Fasinumab Compared to Placebo

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    End point title
    Percentage of Subjects With Greater Than or Equal to (≥) 30 Percent (%) Reduction From Baseline up to Week 24 in WOMAC Pain Subscale Score in Subjects Treated With Fasinumab Compared to Placebo [10]
    End point description
    WOMAC pain subscale was a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index knee during past 48 hours. It was calculated as mean of the scores from 5 individual questions scored on a NRS of 0 (minimum pain) to 10 (maximum pain), where higher scores indicate more pain.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 24
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The fasinumab 3 mg and 6 mg arms were not evaluated as they were discontinued early in the study.
    End point values
    Placebo Fasinumab 1 mg
    Number of subjects analysed
    308
    612
    Units: Percentage of Subjects
        number (not applicable)
    48.7
    59.8
    Statistical analysis title
    Pooled Placebo vs Fasinumab 1 mg
    Statistical analysis description
    A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.05 level. Analyses are based on Cochran-Mantel-Haenszel model.
    Comparison groups
    Fasinumab 1 mg v Placebo
    Number of subjects included in analysis
    920
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0013 [11]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.581
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.195
         upper limit
    2.092
    Notes
    [11] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in Patient Global Assessment (PGA) Score up to Week 24 in Subjects Treated With Fasinumab Compared to Placebo

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    End point title
    Change From Baseline in Patient Global Assessment (PGA) Score up to Week 24 in Subjects Treated With Fasinumab Compared to Placebo [12]
    End point description
    The PGA was a patient-rated assessment of current disease state on a 5-point Likert scale where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (Severe symptoms and inability to carry out most normal activities) and, 5 =very poor (Very severe symptoms which were intolerable and inability to carry out all normal activities). Higher score indicated severe condition. Here, “Number of Subjects Analysed” signifies those subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 24
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only fasinumab 1 mg and placebo were evaluated in this endpoint. The fasinumab 3 mg and 6 mg arms were not evaluated as they were discontinued early in the study.
    End point values
    Placebo Fasinumab 1 mg
    Number of subjects analysed
    214
    440
    Units: Score on a Scale
        least squares mean (standard error)
    -0.66 ± 0.063
    -0.81 ± 0.047
    Statistical analysis title
    Pooled Placebo vs Fasinumab 1 mg
    Statistical analysis description
    A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when the previous endpoint was statistically significant at 0.05 level. Analyses are based on a multiple imputation approach using Mixed-Effect Model With Repeated Measure (MMRM) model.
    Comparison groups
    Placebo v Fasinumab 1 mg
    Number of subjects included in analysis
    654
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0365 [13]
    Method
    MMRM
    Parameter type
    LS Mean Difference
    Point estimate
    -0.14
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.28
         upper limit
    -0.009
    Notes
    [13] - Threshold for significance at 0.05 level.

    Secondary: Change From Baseline in WOMAC Pain Subscale Scores up to Week 24 in Subjects Treated With Fasinumab Compared to Subjects Treated With NSAIDs

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    End point title
    Change From Baseline in WOMAC Pain Subscale Scores up to Week 24 in Subjects Treated With Fasinumab Compared to Subjects Treated With NSAIDs [14]
    End point description
    WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis in the index joint (knee or hip) in the past 48 hours. It is calculated as the mean of the scores from the 5 individual questions scored on a NRS of 0 (no pain) to 10 (higher pain), where higher scores indicated higher pain. Here, “Number of Subjects Analysed” signifies those subjects who were evaluable for this endpoint. The modified full analysis set (mFAS) includes all randomized subjects in the FAS but excludes subjects from four sites for which there were potential concerns regarding data quality, identified prior to database lock.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 24
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only fasinumab 1 mg and NSAIDs were evaluated in this endpoint. The fasinumab 3 mg and 6 mg arms were not evaluated as they were discontinued early in the study.
    End point values
    NSAIDs Fasinumab 1 mg
    Number of subjects analysed
    426
    439
    Units: Score on a Scale
    least squares mean (standard error)
        FAS (n=426, 439)
    -2.60 ± 0.128
    -2.84 ± 0.127
        mFAS (n=363, 372)
    -2.48 ± 0.140
    -2.78 ± 0.141
    No statistical analyses for this end point

    Secondary: Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Subjects Treated With Fasinumab Compared to Subjects Treated With NSAIDs

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    End point title
    Change From Baseline in WOMAC Physical Function Subscale Scores up to Week 24 in Subjects Treated With Fasinumab Compared to Subjects Treated With NSAIDs [15]
    End point description
    Physical function referred to subject's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale was a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimum difficulty) to 10 (maximum difficulty), where higher scores indicated maximum difficulty. Here, “Number of Subjects Analysed” signifies those subjects who were evaluable for this endpoint. The modified full analysis set (mFAS) includes all randomized subjects in the FAS but excludes subjects from four sites for which there were potential concerns regarding data quality, identified prior to database lock.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 24
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only fasinumab 1 mg and NSAIDs were evaluated in this endpoint. The fasinumab 3 mg and 6 mg arms were not evaluated as they were discontinued early in the study.
    End point values
    NSAIDs Fasinumab 1 mg
    Number of subjects analysed
    426
    439
    Units: Score on a Scale
    least squares mean (standard error)
        FAS (n=426, 439)
    -2.33 ± 0.127
    -2.65 ± 0.125
        mFAS (n=364, 372)
    -2.26 ± 0.140
    -2.62 ± 0.138
    No statistical analyses for this end point

    Secondary: Change From Baseline in PGA Score up to Week 24 in Subjects Treated With Fasinumab Compared to Subjects Treated With NSAIDs

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    End point title
    Change From Baseline in PGA Score up to Week 24 in Subjects Treated With Fasinumab Compared to Subjects Treated With NSAIDs [16]
    End point description
    The PGA was a patient-rated assessment of current disease state on a 5-point Likert scale where 1 = very good (asymptomatic and no limitation of normal activities), 2 = good (mild symptoms and no limitation of normal activities), 3 = fair (moderate symptoms and limitation of some normal activities), 4 = poor (Severe symptoms and inability to carry out most normal activities) and, 5 =very poor (Very severe symptoms which were intolerable and inability to carry out all normal activities). Higher score indicated severe condition. Here, “Number of Subjects Analysed” signifies those subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 24
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only fasinumab 1 mg and NSAIDs were evaluated in this endpoint. The fasinumab 3 mg and 6 mg arms were not evaluated as they were discontinued early in the study.
    End point values
    NSAIDs Fasinumab 1 mg
    Number of subjects analysed
    427
    440
    Units: Score on a Scale
        least squares mean (standard error)
    -0.75 ± 0.048
    -0.81 ± 0.047
    No statistical analyses for this end point

    Secondary: Change From Baseline in Weekly Average Walking Index Joint Pain Score up to Week 24 by Using the Numeric Rating Scale (NRS) Pain Scale

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    End point title
    Change From Baseline in Weekly Average Walking Index Joint Pain Score up to Week 24 by Using the Numeric Rating Scale (NRS) Pain Scale [17]
    End point description
    Subjects reported weekly average walking index joint pain based on NRS. The NRS was nationally recognized numeric scale from 0 to 10, where 0 would demonstrate no pain, 1 to 3 would demonstrate mild pain, 4 to 6 would be moderate pain, 7 to 9 would be severe pain and 10 would be the worst pain possible. Higher score indicated greater pain. Here, “Number of Subjects Analysed” signifies those subjects who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 24
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The fasinumab 3 mg and 6 mg arms were not evaluated as they were discontinued early in the study.
    End point values
    Placebo NSAIDs Fasinumab 1 mg
    Number of subjects analysed
    231
    449
    470
    Units: Score on a Scale
        least squares mean (standard error)
    -1.85 ± 0.130
    -2.13 ± 0.101
    -2.51 ± 0.100
    No statistical analyses for this end point

    Secondary: Serum Concentrations of Functional Fasinumab

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    End point title
    Serum Concentrations of Functional Fasinumab [18]
    End point description
    Serum concentrations of functional Fasinumab were reported. Pharmacokinetic (PK) analysis set included all treated subjects who received any study drug and who had at least 1 non-missing drug concentration result following the first study dose. Here, Number of Subjects Analysed” = subjects who were evaluable for this endpoint and “n = subjects who were evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    At Weeks 0, 4, 8, 16, 24 and 44
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only fasinumab 1 mg was evaluated in this endpoint and the fasinumab 3 mg and 6 mg arms were not evaluated as they were discontinued early in the study.
    End point values
    Fasinumab 1 mg
    Number of subjects analysed
    586
    Units: Milligrams per Liter (mg/L)
    arithmetic mean (standard deviation)
        Week 0: (n = 586)
    0.000155 ± 0.002
        Week 4: (n = 570)
    0.0469 ± 0.0179
        Week 8: (n = 543)
    0.0644 ± 0.0275
        Week 16: (n = 502)
    0.0738 ± 0.0380
        Week 24: (n = 465)
    0.0713 ± 0.0379
        Week 44: (n = 186)
    0.000349 ± 0.00476
    No statistical analyses for this end point

    Secondary: Number of Subjects With At-least One Positive Anti-Drug Antibody (ADA) Development

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    End point title
    Number of Subjects With At-least One Positive Anti-Drug Antibody (ADA) Development [19]
    End point description
    Immunogenicity was characterized by ADA responses & titers. Responses categories: Pre-existing immunoreactivity - ADA positive response at baseline with all post first dose negative results or positive response at baseline with all post first dose ADA responses < 9-fold over baseline titer levels; Treatment-boosted response - positive response in the assay post first dose, ≥ 9-fold over baseline titer levels, when baseline results are positive; Treatment-emergent response - ADA positive response post first dose when baseline results = negative or missing. ADA analysis set included all subjects who received any study drug and had at least 1 non-missing ADA result following the first dose of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline up to follow-up period (Week 44)
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The fasinumab 3 mg and 6 mg arms were not evaluated as they were discontinued early in the study.
    End point values
    Placebo NSAIDs Fasinumab 1 mg
    Number of subjects analysed
    291
    568
    569
    Units: Subjects
        Pre-Existing Immunoreactivity
    10
    9
    15
        Treatment-Boosted Response
    0
    0
    0
        Treatment-Emergent Response
    3
    1
    4
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to week 72
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Subjects received SC injection of placebo matched to Fasinumab Q4W or Q8W or oral placebo matched to NSAID BID up to 24 weeks. At time of dosing, two subjects from NSAID cohort received placebo.

    Reporting group title
    NSAIDs
    Reporting group description
    Subjects received oral capsule of Diclofenac at a dose of 75 mg BID or oral capsule of Celecoxib at a dose of 200 mg once daily (QD) up to 24 weeks.

    Reporting group title
    Fasinumab 1mg Q4W
    Reporting group description
    Subjects received SC injection of Fasinumab at a dose of 1 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID

    Reporting group title
    Fasinumab 3mg Q4W
    Reporting group description
    Subjects received SC injection of Fasinumab at a dose of 3 mg Q4W up to 24 weeks and NSAID-matching placebo oral, BID

    Reporting group title
    Fasinumab 6mg Q8W
    Reporting group description
    Subjects received SC injection of Fasinumab at a dose of 6 mg Q8W up to 24 weeks, alternating with Q8W placebo injections. Subjects received placebo injections at the Q4W study visits where study drug was not administered and NSAID-matching placebo oral, BID

    Serious adverse events
    Placebo NSAIDs Fasinumab 1mg Q4W Fasinumab 3mg Q4W Fasinumab 6mg Q8W
    Total subjects affected by serious adverse events
         subjects affected / exposed
    20 / 309 (6.47%)
    45 / 609 (7.39%)
    35 / 609 (5.75%)
    5 / 58 (8.62%)
    2 / 59 (3.39%)
         number of deaths (all causes)
    0
    3
    1
    0
    0
         number of deaths resulting from adverse events
    Vascular disorders
    Arteriosclerosis
         subjects affected / exposed
    1 / 309 (0.32%)
    0 / 609 (0.00%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 309 (0.32%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Varicose vein
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Joint arthroplasty
         subjects affected / exposed
    1 / 309 (0.32%)
    3 / 609 (0.49%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Knee arthroplasty
         subjects affected / exposed
    1 / 309 (0.32%)
    4 / 609 (0.66%)
    2 / 609 (0.33%)
    1 / 58 (1.72%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip arthroplasty
         subjects affected / exposed
    1 / 309 (0.32%)
    3 / 609 (0.49%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Prostate cancer
         subjects affected / exposed
    0 / 309 (0.00%)
    2 / 609 (0.33%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive papillary breast carcinoma
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Impaired healing
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depressed mood
         subjects affected / exposed
    1 / 309 (0.32%)
    0 / 609 (0.00%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine prolapse
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cyst
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Concussion
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 309 (0.32%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fractured sacrum
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Accidental overdose
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 309 (0.32%)
    0 / 609 (0.00%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon injury
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 309 (0.32%)
    2 / 609 (0.33%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 309 (0.32%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    0 / 609 (0.00%)
    1 / 58 (1.72%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 309 (0.32%)
    0 / 609 (0.00%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Amnesia
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 309 (0.00%)
    2 / 609 (0.33%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 309 (0.32%)
    0 / 609 (0.00%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Trigeminal neuralgia
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudostroke
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal detachment
         subjects affected / exposed
    1 / 309 (0.32%)
    0 / 609 (0.00%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo positional
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastritis
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    2 / 609 (0.33%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    1 / 309 (0.32%)
    0 / 609 (0.00%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    1 / 309 (0.32%)
    0 / 609 (0.00%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device loosening
         subjects affected / exposed
    1 / 309 (0.32%)
    0 / 609 (0.00%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device dislocation
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    1 / 58 (1.72%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    3 / 309 (0.97%)
    6 / 609 (0.99%)
    1 / 609 (0.16%)
    1 / 58 (1.72%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoporotic fracture
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rapidly progressive osteoarthritis
         subjects affected / exposed
    2 / 309 (0.65%)
    0 / 609 (0.00%)
    8 / 609 (1.31%)
    2 / 58 (3.45%)
    2 / 59 (3.39%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 9
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 309 (0.00%)
    2 / 609 (0.33%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal synovial cyst
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendonitis
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint range of motion decreased
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal stenosis
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subchondral insufficiency fracture
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    0 / 609 (0.00%)
    1 / 58 (1.72%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 309 (0.00%)
    2 / 609 (0.33%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection staphylococcal
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 309 (0.00%)
    1 / 609 (0.16%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 309 (0.32%)
    0 / 609 (0.00%)
    0 / 609 (0.00%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningitis viral
         subjects affected / exposed
    0 / 309 (0.00%)
    0 / 609 (0.00%)
    1 / 609 (0.16%)
    0 / 58 (0.00%)
    0 / 59 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Placebo NSAIDs Fasinumab 1mg Q4W Fasinumab 3mg Q4W Fasinumab 6mg Q8W
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    121 / 309 (39.16%)
    263 / 609 (43.19%)
    261 / 609 (42.86%)
    17 / 58 (29.31%)
    15 / 59 (25.42%)
    Injury, poisoning and procedural complications
    Ligament sprain
         subjects affected / exposed
    2 / 309 (0.65%)
    4 / 609 (0.66%)
    5 / 609 (0.82%)
    0 / 58 (0.00%)
    3 / 59 (5.08%)
         occurrences all number
    2
    4
    5
    0
    3
    Muscle strain
         subjects affected / exposed
    0 / 309 (0.00%)
    4 / 609 (0.66%)
    6 / 609 (0.99%)
    3 / 58 (5.17%)
    1 / 59 (1.69%)
         occurrences all number
    0
    5
    7
    3
    1
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    3 / 309 (0.97%)
    5 / 609 (0.82%)
    5 / 609 (0.82%)
    3 / 58 (5.17%)
    3 / 59 (5.08%)
         occurrences all number
    3
    5
    5
    3
    3
    Nervous system disorders
    Headache
         subjects affected / exposed
    48 / 309 (15.53%)
    107 / 609 (17.57%)
    95 / 609 (15.60%)
    2 / 58 (3.45%)
    2 / 59 (3.39%)
         occurrences all number
    113
    210
    224
    2
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    36 / 309 (11.65%)
    78 / 609 (12.81%)
    82 / 609 (13.46%)
    4 / 58 (6.90%)
    3 / 59 (5.08%)
         occurrences all number
    53
    102
    109
    7
    3
    Back pain
         subjects affected / exposed
    17 / 309 (5.50%)
    44 / 609 (7.22%)
    46 / 609 (7.55%)
    1 / 58 (1.72%)
    1 / 59 (1.69%)
         occurrences all number
    17
    60
    51
    1
    1
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    25 / 309 (8.09%)
    35 / 609 (5.75%)
    50 / 609 (8.21%)
    1 / 58 (1.72%)
    2 / 59 (3.39%)
         occurrences all number
    29
    39
    57
    1
    2
    Nasopharyngitis
         subjects affected / exposed
    22 / 309 (7.12%)
    38 / 609 (6.24%)
    29 / 609 (4.76%)
    2 / 58 (3.45%)
    1 / 59 (1.69%)
         occurrences all number
    26
    44
    35
    2
    1
    Upper respiratory tract infection
         subjects affected / exposed
    15 / 309 (4.85%)
    30 / 609 (4.93%)
    30 / 609 (4.93%)
    3 / 58 (5.17%)
    1 / 59 (1.69%)
         occurrences all number
    18
    31
    33
    3
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 May 2018
    To incorporate an urgent safety measure, which requires discontinuing the 3 mg Q4W and 6 mg Q8W dose regimens. The recommendation by the independent Data Monitoring Committee (DMC) to discontinue these dose regimens was made following a review of unblinded data from an ongoing study in the fasinumab phase 3 osteoarthritis program (R475-PN-1523) and was based on an imbalance in clinically relevant adverse events including time to total joint replacement, peripheral edema, arthralgia and a trend towards early fractures in the 6 mg Q8W group. Based on the independent DMC review, study of lower dose levels (eg, 1 mg Q4W) may continue to be evaluated in this population. With this amendment, subjects randomised to the 3 mg Q4W or 6 mg Q8W dose regimens will be permanently discontinued from study drug but encouraged to otherwise complete all remaining study visits and study procedures in the follow up period and the end of study phone call.
    11 Jul 2018
    Updated reasons for permanent discontinuation of study drug to ensure subjects enrolled under earlier protocol version were immediately discontinued from study drug and moved to follow-up period if they met updated exclusion criteria or were taking newly added prohibited medications.

    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.
    5/2018: Urgent safety measure to stop dosing Fasinumab 3 & 6mg, to prevent further randomisation to these regimens across Fasinumab program. Subjects randomised to fasinumab 3 & 6mg discontinued from study drug & moved directly into follow-up period.
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