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    Clinical Trial Results:
    A Single-Arm, Open-Label Study To Assess The Immunogenicity, Safety, And Efficacy Of Etanercept Manufactured Using The High Capacity Process Administered To Subjects With Rheumatoid Arthritis

    Summary
    EudraCT number
    2013-004569-16
    Trial protocol
    HU   SK   DE   BG   GR   HR  
    Global end of trial date
    18 Jun 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    05 Apr 2017
    First version publication date
    05 Apr 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    B1801359
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02378506
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001  800­-718­-1021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001  800­-718­-1021, ClinicalTrials.gov_Inquiries@pfizer.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
    27 Jan 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Jun 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the immunogenicity of Etanercept manufactured using the high capacity process administered weekly in subjects with rheumatoid arthritis over 24 weeks.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    02 Apr 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Bulgaria: 19
    Country: Number of subjects enrolled
    Croatia: 19
    Country: Number of subjects enrolled
    Germany: 29
    Country: Number of subjects enrolled
    Greece: 4
    Country: Number of subjects enrolled
    Hungary: 13
    Country: Number of subjects enrolled
    Poland: 24
    Country: Number of subjects enrolled
    Serbia: 8
    Country: Number of subjects enrolled
    Slovakia: 39
    Country: Number of subjects enrolled
    South Africa: 32
    Worldwide total number of subjects
    187
    EEA total number of subjects
    147
    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)
    142
    From 65 to 84 years
    45
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    188 subjects were randomized, however only 187 were treated.

    Period 1
    Period 1 title
    Over All (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Etanercept
    Arm description
    Subjects with moderate to severe rheumatoid arthritis (RA), received subcutaneous Etanercept 50 milligram (mg) once weekly up to Week 24 and were followed up to Week 28.
    Arm type
    Experimental

    Investigational medicinal product name
    Etanercept
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received subcutaneous Etanercept 50 mg once weekly up to Week 24.

    Number of subjects in period 1
    Etanercept
    Started
    187
    Completed
    163
    Not completed
    24
         Death
    1
         Protocol deviation
    2
         Lack of efficacy
    3
         Consent withdrawn by subject
    4
         Adverse Event
    14

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Etanercept
    Reporting group description
    Subjects with moderate to severe rheumatoid arthritis (RA), received subcutaneous Etanercept 50 milligram (mg) once weekly up to Week 24 and were followed up to Week 28.

    Reporting group values
    Etanercept Total
    Number of subjects
    187 187
    Age Categorical
    Units: Subjects
        In utero
    0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0
        Newborns (0-27 days)
    0 0
        Infants and toddlers (28 days-23 months)
    0 0
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    142 142
        From 65-84 years
    45 45
        85 years and over
    0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    54.2 ± 12.89 -
    Gender Categorical
    Units: Subjects
        Female
    159 159
        Male
    28 28

    End points

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    End points reporting groups
    Reporting group title
    Etanercept
    Reporting group description
    Subjects with moderate to severe rheumatoid arthritis (RA), received subcutaneous Etanercept 50 milligram (mg) once weekly up to Week 24 and were followed up to Week 28.

    Primary: Percentage of Subjects With Positive Etanercept Anti-Drug Antibody (ADA) Status at Week 12

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    End point title
    Percentage of Subjects With Positive Etanercept Anti-Drug Antibody (ADA) Status at Week 12 [1]
    End point description
    Subjects who developed anti-drug antibodies after treatment with Etanercept were evaluated. Percentage of subjects with positive anti-drug antibodies were summarized. Analysis set included all subjects who had taken at least 1 dose of study medication and had at least 1 Etanercept anti-drug antibody evaluation. Here, ‘Number of Subjects Analyzed' (N) signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Week 12
    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: Only descriptive data was planned to be analyzed in this endpoint
    End point values
    Etanercept
    Number of subjects analysed
    158
    Units: percentage of subjects
        number (confidence interval 95%)
    1.9 (0.5 to 5)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Positive Etanercept Anti-Drug Antibody (ADA) Status at Week 24

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    End point title
    Percentage of Subjects With Positive Etanercept Anti-Drug Antibody (ADA) Status at Week 24 [2]
    End point description
    Subjects who developed anti-drug antibodies after treatment with Etanercept were evaluated. Percentage of subjects with positive anti-drug antibodies were summarized. Analysis set included all subjects who had taken at least 1 dose of study medication and had at least 1 Etanercept anti-drug antibody evaluation. Here, ‘N’ signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Week 24
    Notes
    [2] - 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: Only descriptive data was planned to be analyzed in this endpoint
    End point values
    Etanercept
    Number of subjects analysed
    175
    Units: percentage of subjects
        number (confidence interval 95%)
    2.9 (1.1 to 6.1)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Positive Etanercept Anti-Drug Antibody (ADA) Status: Throughout Study Treatment

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    End point title
    Percentage of Subjects With Positive Etanercept Anti-Drug Antibody (ADA) Status: Throughout Study Treatment [3]
    End point description
    Subjects who developed anti-drug antibodies after treatment with Etanercept were evaluated. Percentage of subjects with positive anti-drug antibodies were summarized. Analysis set included all subjects who had taken at least 1 dose of study medication and had at least 1 Etanercept anti-drug antibody evaluation.
    End point type
    Primary
    End point timeframe
    Baseline up to Week 24
    Notes
    [3] - 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: Only descriptive data was planned to be analyzed in this endpoint
    End point values
    Etanercept
    Number of subjects analysed
    176
    Units: percentage of subjects
        number (confidence interval 95%)
    4.5 (2.2 to 8.4)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Positive Etanercept Neutralizing Anti-drug Antibody Status: Throughout Study Treatment

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    End point title
    Percentage of Subjects With Positive Etanercept Neutralizing Anti-drug Antibody Status: Throughout Study Treatment
    End point description
    Percentage of subjects with positive Etanercept neutralizing anti-drug antibodies were summarized. Analysis set included all subjects who had taken at least 1 dose of study medication and had at least 1 Etanercept anti-drug antibody evaluation.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) up to Week 24
    End point values
    Etanercept
    Number of subjects analysed
    176
    Units: percentage of subjects
        number (confidence interval 95%)
    0 (0 to 1.4)
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

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    End point title
    Number of Subjects With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events. Safety population included all subjects who had taken at least 1 dose of study medication.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) up to Week 28 (Follow-up)
    End point values
    Etanercept
    Number of subjects analysed
    187
    Units: subjects
    number (not applicable)
        AEs
    90
        SAEs
    9
    No statistical analyses for this end point

    Secondary: Number of Subjects With Investigator-Identified Serious Infections

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    End point title
    Number of Subjects With Investigator-Identified Serious Infections
    End point description
    Infection was considered as serious by investigator for any of the following outcomes: death; life-threatening; required initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity or congenital anomaly/birth defect. Safety population included all subjects who had taken at least 1 dose of study medication.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) up to Week 28 (Follow-up)
    End point values
    Etanercept
    Number of subjects analysed
    187
    Units: subjects
        number (not applicable)
    3
    No statistical analyses for this end point

    Secondary: Number of Subjects With Injection Site Reactions

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    End point title
    Number of Subjects With Injection Site Reactions
    End point description
    Injection site reactions included injection site erythema, swelling, pain, and warmth. Safety population included all subjects who had taken at least 1 dose of study medication.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) up to Week 28 (Follow-up)
    End point values
    Etanercept
    Number of subjects analysed
    187
    Units: subjects
        number (not applicable)
    27
    No statistical analyses for this end point

    Secondary: Number of Subjects With Grade 3 and 4 Clinical Laboratory Abnormalities

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    End point title
    Number of Subjects With Grade 3 and 4 Clinical Laboratory Abnormalities
    End point description
    Laboratory abnormalities (national cancer institute toxicity criteria version 4.0), Grade 3: neutrophil (>=0.5, <1.0 10^9/L), lymphocyte (<0.5 10^9/L), hemoglobin (Hb) (<80, >=65 gram per liter [g/L]), platelet (<50.0, >=25.0 10^9/L), white blood count (WBC) (<2.0, >=1.0 10^9/L); alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) (>5.0*upper range [UR], <=20.0*UR unit per liter [U/L]); bilirubin (>1.5*UR, <=3.0*UR micromole per liter [mcmol/L]); creatinine (>3.0*UR, <=6.0* UR mcmol/L); albumin (<20.0 g/L), urea (>3.0* UR, <=4.0* UR g/L); potassium (K)-high, low (>6.0, <=7.0 or <3.0, >=2.5 mcmol/L); sodium (Na)-high, low (>155, <=160 or <130, >=120 mcmol/L) and Grade 4: neutrophil(<0.5 10^9/L), Hb(<65 g/L); platelet(<25.0 10^9/L); WBC(<1.0 10^9/L); AP, AST, ALT(>20.0*UR U/L); bilirubin(>3.0* UR mcmol/L); creatinine(>6.0* UR mcmol/L); urea(>4.0* UR g/L); K-high, low(>7.0 or <2.5 mcmol/L); Na-high, low(>160 or <120 mcmol/L). Safety population.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) up to Week 28 (Follow-up)
    End point values
    Etanercept
    Number of subjects analysed
    187
    Units: subjects
        number (not applicable)
    5
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieving American College of Rheumatology 20% (ACR20) Response

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    End point title
    Percentage of Subjects Achieving American College of Rheumatology 20% (ACR20) Response
    End point description
    ACR20 responder: subjects with 20% improvement in tender, swollen 28-joint counts, 20% improvement in at least 3 of 5 measures: subject global assessment of arthritis (subject assessed overall arthritis, score: 0 [no arthritis] to 10 [extreme arthritis], higher score=more arthritis); physician global assessment of arthritis (physician judged subject’s overall arthritis, score: 0 [no arthritis] to 10 [extreme arthritis], higher score=more arthritis); subject pain visual analogue scale (VAS) (subject assessed arthritis pain by 100 millimeter (mm) VAS, score: 0 mm [no pain] to 100 mm [extreme pain], higher score=more pain); health assessment questionnaire-disability index (functional disability evaluation, score: 0 [no difficulty] to 3 [extreme difficulty], higher score=more disability); C-reactive protein. Percentage of subjects with ACR20 response were reported. mITT. n = number of subjects evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Week 4, 12, 24
    End point values
    Etanercept
    Number of subjects analysed
    187
    Units: percentage of subjects
    number (confidence interval 95%)
        Week 4 (n =186)
    55.9 (48.7 to 62.9)
        Week 12 (n =179)
    76.5 (69.9 to 82.3)
        Week 24 (n =161)
    82 (75.5 to 87.3)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieving American College of Rheumatology 50% (ACR50) Response

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    End point title
    Percentage of Subjects Achieving American College of Rheumatology 50% (ACR50) Response
    End point description
    ACR50 responder: subjects with 50% improvement in tender, swollen 28-joint counts, 50% improvement in at least 3 of 5 measures: subject global assessment of arthritis (subject assessed overall arthritis, score: 0 [no arthritis] to 10 [extreme arthritis], higher score=more arthritis); physician global assessment of arthritis (physician judged subject’s overall arthritis, score: 0 [no arthritis] to 10 [extreme arthritis], higher score=more arthritis); subject pain visual analogue scale (VAS) (subject assessed arthritis pain by 100 millimeter (mm) VAS, score: 0 mm [no pain] to 100 mm [extreme pain], higher score=more pain); health assessment questionnaire-disability index (functional disability evaluation, score: 0 [no difficulty] to 3 [extreme difficulty], higher score=more disability); C-reactive protein. Percentage of subjects with ACR50 response were reported. mITT. n = number of subjects evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Week 4, 12, 24
    End point values
    Etanercept
    Number of subjects analysed
    187
    Units: percentage of subjects
    number (confidence interval 95%)
        Week 4 (n =186)
    16.1 (11.4 to 21.9)
        Week 12 (n =179)
    36.3 (29.5 to 43.5)
        Week 24 (n =161)
    57.8 (50.1 to 65.2)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieving American College of Rheumatology 70% (ACR70) Response

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    End point title
    Percentage of Subjects Achieving American College of Rheumatology 70% (ACR70) Response
    End point description
    ACR70 responder: subjects with 70% improvement in tender, swollen 28-joint counts, 70% improvement in at least 3 of 5 measures: subject global assessment of arthritis (subject assessed overall arthritis, score: 0 [no arthritis] to 10 [extreme arthritis], higher score=more arthritis); physician global assessment of arthritis (physician judged subject’s overall arthritis, score: 0 [no arthritis] to 10 [extreme arthritis], higher score=more arthritis); subject pain visual analogue scale (VAS) (subject assessed arthritis pain by 100 millimeter (mm) VAS, score: 0 mm [no pain] to 100 mm [extreme pain], higher score=more pain); health assessment questionnaire-disability index (functional disability evaluation, score: 0 [no difficulty] to 3 [extreme difficulty], higher score=more disability); C-reactive protein. Percentage of subjects with ACR70 response were reported. mITT. n = number of subjects evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Week 4, 12, 24
    End point values
    Etanercept
    Number of subjects analysed
    187
    Units: percentage of subjects
    number (confidence interval 95%)
        Week 4 (n =186)
    3.2 (1.4 to 6.5)
        Week 12 (n =179)
    13.4 (9 to 19)
        Week 24 (n =161)
    26.7 (20.3 to 33.9)
    No statistical analyses for this end point

    Secondary: Change From Baseline in Disease Activity Scale Based on 28 Joint Count Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Week 4, 12 and 24

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    End point title
    Change From Baseline in Disease Activity Scale Based on 28 Joint Count Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Week 4, 12 and 24
    End point description
    DAS28: measure of disease activity in subjects with rheumatoid arthritis. DAS28¬4 (ESR) was calculated from number of swollen joints (SJC) and tender joints (TJC ) using the 28 joints count, erythrocyte sedimentation rate (millimeter per hour [mm/hour]) and subject's general health visual analog scale assessment (scores: 0 mm [very well] to 100 mm [extremely bad], higher scores indicate worse health condition). Total DAS28¬4 (ESR) score: 0 (none) to 10 (extreme disease activity), higher scores indicate more disease activity. DAS28-4 (ESR) less than (<) 2.6= remission, <3.2= low disease activity, greater than or equal to (>=) 3.2 to 5.1= moderate disease activity and >5.1= high disease activity. Modified intent-to-treat (mITT) population included all subjects who had taken at least 1 dose of study medication. Here, “n” signifies number of subjects evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, 12, 24
    End point values
    Etanercept
    Number of subjects analysed
    187
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n =187)
    6.2 ± 0.93
        Change at Week 4 (n =186)
    -1.5 ± 1.04
        Change at Week 12 (n =180)
    -2.3 ± 1.19
        Change at Week 24 (n =162)
    -2.8 ± 1.27
    No statistical analyses for this end point

    Secondary: Change From Baseline in Disease Activity Scale Based on 28 Joint Count C-Reactive Protein (4 Variables) (DAS28-4 [CRP]) at Week 4, 12 and 24

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    End point title
    Change From Baseline in Disease Activity Scale Based on 28 Joint Count C-Reactive Protein (4 Variables) (DAS28-4 [CRP]) at Week 4, 12 and 24
    End point description
    DAS28 is a measure of disease activity in subjects with rheumatoid arthritis. DAS28-4 (CRP) was calculated from the number of swollen joints and tender joints using the 28 joints count, C-Reactive protein (milligram per liter [mg/L]) and subject's general health visual analog scale assessment (scores ranging 0 mm [very well] to 100 mm [extremely bad], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 10 (extreme disease activity), higher scores indicate more disease activity. DAS28-4 (CRP) less than (<) 2.6= remission, <3.2= low disease activity, greater than or equal to (≥) 3.2 to 5.1= moderate disease activity and >5.1= high disease activity. mITT population included all subjects who had taken at least 1 dose of study medication. Here, “n” signifies number of subjects evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, 12, 24
    End point values
    Etanercept
    Number of subjects analysed
    187
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n =187)
    5.4 ± 0.91
        Change at Week 4 (n =187)
    -1.5 ± 1.02
        Change at Week 12 (n =179)
    -2.2 ± 1.09
        Change at Week 24 (n =162)
    -2.5 ± 1.17
    No statistical analyses for this end point

    Secondary: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 4, 12 and 24

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    End point title
    Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 4, 12 and 24
    End point description
    HAQ-DI assesses the degree of difficulty a subject has experienced during the past week in 8 domains of daily living activities: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each item scored on 4-point scale from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities. mITT population included all subjects who had taken at least 1 dose of study medication. Here, “n” signifies number of subjects evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, 12, 24
    End point values
    Etanercept
    Number of subjects analysed
    187
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n =186)
    1.3 ± 0.58
        Change at Week 4 (n =186)
    -0.3 ± 0.39
        Change at Week 12 (n =179)
    -0.4 ± 0.48
        Change at Week 24 (n =161)
    -0.5 ± 0.56
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline (Day 1) up to Week 28 (follow-up)
    Adverse event reporting additional description
    The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as non serious in another subject, or one subject may have experienced both a serious and non serious event during the study.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Etanercept
    Reporting group description
    Subjects with moderate to severe rheumatoid arthritis (RA), received subcutaneous Etanercept 50 milligram (mg) once weekly up to Week 24 and were followed up to Week 28.

    Serious adverse events
    Etanercept
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 187 (4.81%)
         number of deaths (all causes)
    1
         number of deaths resulting from adverse events
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Cardiac failure acute
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Major depression
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Calculus ureteric
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    Urticaria
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Metatarsalgia
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Diverticulitis
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Etanercept
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    85 / 187 (45.45%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Hypertension
         subjects affected / exposed
    4 / 187 (2.14%)
         occurrences all number
    4
    Surgical and medical procedures
    Tooth extraction
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    5 / 187 (2.67%)
         occurrences all number
    5
    Influenza like illness
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Injection site erythema
         subjects affected / exposed
    20 / 187 (10.70%)
         occurrences all number
    46
    Injection site nodule
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    5
    Injection site pruritus
         subjects affected / exposed
    7 / 187 (3.74%)
         occurrences all number
    7
    Injection site rash
         subjects affected / exposed
    2 / 187 (1.07%)
         occurrences all number
    5
    Injection site reaction
         subjects affected / exposed
    5 / 187 (2.67%)
         occurrences all number
    5
    Injection site swelling
         subjects affected / exposed
    3 / 187 (1.60%)
         occurrences all number
    9
    Injection site urticaria
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Injection site vesicles
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Malaise
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Peripheral swelling
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Depression
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Impulsive behaviour
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Reproductive system and breast disorders
    Amenorrhoea
    Additional description: This event was gender specific.
         subjects affected / exposed [1]
    1 / 159 (0.63%)
         occurrences all number
    1
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Contusion
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    2
    Fall
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Foot fracture
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Ligament sprain
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 187 (1.07%)
         occurrences all number
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Blood pressure diastolic abnormal
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Neutrophil count decreased
         subjects affected / exposed
    2 / 187 (1.07%)
         occurrences all number
    2
    Platelet count decreased
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Vitamin D decreased
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    White blood cell count decreased
         subjects affected / exposed
    3 / 187 (1.60%)
         occurrences all number
    3
    Cardiac disorders
    Sinus bradycardia
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Tachycardia
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    2 / 187 (1.07%)
         occurrences all number
    2
    Cough
         subjects affected / exposed
    2 / 187 (1.07%)
         occurrences all number
    2
    Upper-airway cough syndrome
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Neutropenia
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Thrombocytopenia
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Nervous system disorders
    Cerebrovascular disorder
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Headache
         subjects affected / exposed
    5 / 187 (2.67%)
         occurrences all number
    5
    Migraine
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Neuralgia
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Paraesthesia
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Eye disorders
    Retinal detachment
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    3 / 187 (1.60%)
         occurrences all number
    3
    Stomatitis
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Hepatobiliary disorders
    Hepatic cyst
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Hepatic steatosis
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Dermatitis allergic
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    2
    Erythema
         subjects affected / exposed
    4 / 187 (2.14%)
         occurrences all number
    4
    Pruritus
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Pruritus generalised
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Psoriasis
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Rash
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Rash macular
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Rash pruritic
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Skin fissures
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 187 (1.60%)
         occurrences all number
    3
    Back pain
         subjects affected / exposed
    2 / 187 (1.07%)
         occurrences all number
    2
    Joint instability
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Muscle spasms
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Myalgia
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Rheumatoid arthritis
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Iron deficiency
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Infections and infestations
    Asymptomatic bacteriuria
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Bronchitis
         subjects affected / exposed
    3 / 187 (1.60%)
         occurrences all number
    3
    Fungal skin infection
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Gastroenteritis
         subjects affected / exposed
    2 / 187 (1.07%)
         occurrences all number
    2
    Genitourinary tract infection
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Gingivitis
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Herpes zoster
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Influenza
         subjects affected / exposed
    2 / 187 (1.07%)
         occurrences all number
    2
    Nasopharyngitis
         subjects affected / exposed
    13 / 187 (6.95%)
         occurrences all number
    16
    Otitis media acute
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Pneumonia
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Rhinitis
         subjects affected / exposed
    1 / 187 (0.53%)
         occurrences all number
    1
    Tonsillitis
         subjects affected / exposed
    2 / 187 (1.07%)
         occurrences all number
    2
    Upper respiratory tract infection
         subjects affected / exposed
    13 / 187 (6.95%)
         occurrences all number
    14
    Urinary tract infection
         subjects affected / exposed
    4 / 187 (2.14%)
         occurrences all number
    4
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This event was gender specific

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    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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