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    Clinical Trial Results:
    A Randomized, Double-blind, Phase 3 Study of ABP 501 Efficacy and Safety Compared to Adalimumab in Subjects with Moderate to Severe Rheumatoid Arthritis

    Summary
    EudraCT number
    2013-000525-31
    Trial protocol
    GB   CZ   ES   DE   HU   PL   BG   RO  
    Global end of trial date
    19 Nov 2014

    Results information
    Results version number
    v1(current)
    This version publication date
    25 Jun 2016
    First version publication date
    25 Jun 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    20120262
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01970475
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Amgen, Inc.
    Sponsor organisation address
    One Amgen Center Drive, Thousand Oaks, CA, United States, 91320
    Public contact
    IHQ Medical Info-Clinical Trials, Amgen (Europe) GmbH, Medinfointernational@amgen.com
    Scientific contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, Medinfointernational@amgen.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
    19 Nov 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Nov 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective for this study is to assess the efficacy of ABP 501 compared with adalimumab.
    Protection of trial subjects
    This study was conducted in accordance with the Note for Guidance on GCP (ICH Harmonised Tripartite Guideline E6 [R1]; FDA CFR [21 CFR § 50, 56, 312]), the general guidelines indicated in the Declaration of Helsinki and all applicable regulatory requirements. This study was conducted in compliance with Institutional Review Board (IRB)/Independent Ethics Committee (IEC) and ICH GCP Guidelines - including Title 21 Part 56 of the US Code of Federal Regulations (CFR) relating to IRBs/IECs and GCP as described in the US FDA Code of Federal Regulations CFR (21 CFR § 50, 56, 312) - in accordance with applicable ICH regulations regarding clinical safety data management (E2A, E2B[R3]), European Community directives 2001/20, 2001/83, 2003/94 and 2005/28 as enacted into local law, and with ICH guidelines regarding scientific integrity (E4, E8, E9, and E10). In addition, this study was conducted in adherence to all local regulatory requirements, and requirements for data protection. Before initiating the study, the investigator/institution obtained written and dated approval/favorable opinion from the IRB/IEC for the study protocol/amendments, written informed consent form, any consent form updates, subject recruitment procedures (eg, advertisements), and any written information provided to subjects and a statement from the IRB/IEC that they comply with GCP requirements. The investigator explained the benefits and risks of participation in the study to each subject or the subject’s legally acceptable representative and obtained written informed consent before the subject entered the study and before initiation of any study related procedure.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    24 Oct 2013
    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
    Spain: 18
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    United States: 137
    Country: Number of subjects enrolled
    Bulgaria: 19
    Country: Number of subjects enrolled
    Canada: 7
    Country: Number of subjects enrolled
    Czech Republic: 58
    Country: Number of subjects enrolled
    Germany: 22
    Country: Number of subjects enrolled
    Hungary: 57
    Country: Number of subjects enrolled
    Mexico: 3
    Country: Number of subjects enrolled
    Poland: 197
    Country: Number of subjects enrolled
    Romania: 4
    Country: Number of subjects enrolled
    Russian Federation: 2
    Worldwide total number of subjects
    526
    EEA total number of subjects
    377
    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)
    402
    From 65 to 84 years
    124
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    This was a randomized, double-blind, active comparator-controlled study of adalimumab-naïve adults with moderate to severe rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX). This study was conducted at 92 centers in 12 countries.

    Pre-assignment
    Screening details
    Participants were randomized 1:1 to receive either ABP 501 or adalimumab at 40 mg every 2 weeks for 22 weeks. The assessment of the primary endpoint was at week 24, with a safety follow-up period through week 26. Randomization was stratified by geographic region and prior biologic use for RA (capped at 40% of the study population).

    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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    ABP 501
    Arm description
    Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.
    Arm type
    Experimental

    Investigational medicinal product name
    ABP 501
    Investigational medicinal product code
    ABP 501
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    40 mg subcutaneous injection every 2 weeks

    Arm title
    Adalimumab
    Arm description
    Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.
    Arm type
    Active comparator

    Investigational medicinal product name
    Adalimumab
    Investigational medicinal product code
    Other name
    Humira
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    40 mg subcutaneous injection every 2 weeks

    Number of subjects in period 1
    ABP 501 Adalimumab
    Started
    264
    262
    Completed
    243
    251
    Not completed
    21
    11
         Protocol violation
    1
    -
         Other - adverse event
    7
    3
         Consent withdrawn by subject
    11
    6
         Lost to follow-up
    2
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    ABP 501
    Reporting group description
    Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.

    Reporting group title
    Adalimumab
    Reporting group description
    Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.

    Reporting group values
    ABP 501 Adalimumab Total
    Number of subjects
    264 262 526
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    205 197 402
        From 65-84 years
    59 65 124
        85 years and over
    0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    55.4 ± 11.88 56.3 ± 11.47 -
    Gender categorical
    Units: Subjects
        Female
    214 212 426
        Male
    50 50 100
    Race
    Units: Subjects
        White
    251 249 500
        Black or African American
    9 12 21
        Asian
    3 0 3
        American Indian or Alaska Native
    0 0 0
        Native Hawaiian or Other Pacific Islander
    0 0 0
        Other
    1 1 2
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    33 25 58
        Not Hispanic or Latino
    230 236 466
        Not Allowed to Collect
    1 1 2
    Geographic Region
    Units: Subjects
        Eastern Europe
    169 168 337
        Western Europe
    22 20 42
        North America
    72 72 144
        Latin America
    1 2 3
    Prior Biological use for RA
    Units: Subjects
        Yes
    71 74 145
        No
    193 188 381
    Duration of RA
    Units: years
        arithmetic mean (standard deviation)
    9.41 ± 8.076 9.37 ± 8.047 -
    Disease Activity Score 28-C-Reactive Protein (DAS28-CRP)
    The DAS28-CRP is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: • The number of swollen and tender joints assessed using the 28-joint count; • C-reactive protein (CRP) level • Patient's global assessment of disease activity assessed on a score from 0 to 100 transformed from the result measured on a horizontal scale from 0 (no RA activity at all) to 10 (worst RA activity imaginable). The DAS28-CRP score ranges from approximately zero to ten. Higher scores indicate higher disease activity.
    Units: units on a scale
        arithmetic mean (standard deviation)
    5.66 ± 0.918 5.68 ± 0.911 -
    Swollen Joint Count
    Sixty-six joints were assessed and classified as swollen/not swollen by pressure and joint manipulation on physical examination.
    Units: joints
        arithmetic mean (standard deviation)
    14.7 ± 9.05 14.1 ± 7.98 -
    Tender Joint Count
    Sixty-eight joints were assessed and classified as tender/not tender by pressure and joint manipulation on physical examination.
    Units: joints
        arithmetic mean (standard deviation)
    24.3 ± 14.35 23.9 ± 13.49 -
    Subject Global Health Assessment
    The participant's overall assessment of their disease activity in the past week on a 0 to 10 horizontal scale. The left-hand extreme of the scale was described as "no RA activity at all" (symptom-free and no arthritis symptoms; score = 0) and the right-hand extreme as "worst RA activity imaginable" (maximum arthritis disease activity; score = 10).
    Units: units on a scale
        arithmetic mean (standard deviation)
    6.5 ± 1.92 6.6 ± 1.86 -
    Investigator Global Health Assessment
    The Investigator's assessment of the participant's current disease activity on a 0 to 10 horizontal scale. The left-hand extreme of the scale was described as "no activity at all" (symptom-free and no arthritis symptoms; score = 0) and the right-hand extreme as "worst activity imaginable" (maximum arthritis disease activity; score = 10).
    Units: units on a scale
        arithmetic mean (standard deviation)
    6.8 ± 1.29 6.7 ± 1.59 -
    Subject's assessment of disease related pain
    The subject's assessment of their current level of pain on a 100-mm horizontal visual analogue scale (VAS). The left-hand extreme of the line was described as "no pain at all" (score = 0) and the right-hand extreme as "worst pain imaginable" (score = 100).
    Units: mm
        arithmetic mean (standard deviation)
    58.3 ± 21.82 60.6 ± 22.37 -
    Health Assessment Questionnaire-Disability Index (HAQ-DI)
    The HAQ-DI is a questionnaire on which participants are asked to rate their level of difficulty on daily activities (dressing and grooming, arising, eating, and walking) and personal abilities (hygiene, reach, grip, and activity) as well as their use of aids, devices, or help from another person for these activities and disabilities. Responses are scored from 0 indicating no difficulty to 3 indicating inability to perform a task in that area. The overall score is the average of each of the 8 category scores and ranges from 0 (no disability) to 3 (very severe, high-dependency disability).
    Units: units on a scale
        arithmetic mean (standard deviation)
    1.4819 ± 0.61715 1.4976 ± 0.64743 -
    C-reactive Protein
    Units: mg/L
        arithmetic mean (standard deviation)
    13.881 ± 20.687 14.678 ± 19.3848 -

    End points

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    End points reporting groups
    Reporting group title
    ABP 501
    Reporting group description
    Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.

    Reporting group title
    Adalimumab
    Reporting group description
    Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.

    Primary: Percentage of Participants with an American College of Rheumatology (ACR) 20 Response at Week 24

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    End point title
    Percentage of Participants with an American College of Rheumatology (ACR) 20 Response at Week 24
    End point description
    A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in tender joint count; • ≥ 20% improvement in swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Subject's assessment of pain (measured on a 100 mm VAS); ◦ Subject's Global Health Assessment (measured on a horizontal scale from 0 to 10); ◦ Investigator's Global Health Assessment (measured on a horizontal scale from 0 to 10); ◦ Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; ◦ C-reactive protein level. For the primary analysis based on the full analysis set (all randomized participants), missing values were imputed using the last observation carried forward (LOCF) method.
    End point type
    Primary
    End point timeframe
    Baseline and Week 24
    End point values
    ABP 501 Adalimumab
    Number of subjects analysed
    264 [1]
    262 [2]
    Units: percentage of participants
        number (not applicable)
    74.6
    72.4
    Notes
    [1] - Participants who were randomized and had at least 1 post-baseline assessment up to Week 24 (n = 260)
    [2] - Participants who were randomized and had at least 1 post-baseline assessment up to Week 24 (n = 261)
    Statistical analysis title
    Analysis of ACR20 at Week 24
    Statistical analysis description
    Clinical equivalence for the primary endpoint, the risk ratio (RR) of ACR20 at week 24, was evaluated by comparing the 2-sided 90% confidence interval (CI) of the RR of ACR20 between ABP 501 and adalimumab with an equivalence margin of (0.738, 1/0.738). The 90% CI was estimated using a generalized linear model (specifically, a log-binomial regression model), adjusted for geographic region and prior biological use for RA as covariates in the model.
    Comparison groups
    ABP 501 v Adalimumab
    Number of subjects included in analysis
    526
    Analysis specification
    Pre-specified
    Analysis type
    equivalence
    Method
    Parameter type
    Risk ratio (RR)
    Point estimate
    1.039
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.954
         upper limit
    1.133

    Secondary: Change from Baseline in Disease Activity Score 28-C-Reactive Protein (DAS28-CRP)

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    End point title
    Change from Baseline in Disease Activity Score 28-C-Reactive Protein (DAS28-CRP)
    End point description
    The DAS28-CRP is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: • The number of swollen and tender joints assessed using the 28-joint count; • C-reactive protein (CRP) level • Patient's global assessment of disease activity assessed on a score from 0 to 100 transformed from the result measured on a horizontal scale from 0 (no RA activity at all) to 10 (worst RA activity imaginable). The DAS28-CRP score ranges from approximately zero to ten. Higher DAS28-CRP scores indicate higher disease activity. A repeated measures analysis with the DAS28-CRP change from baseline as the response and the stratification variables, visit, treatment, treatment-by-visit interaction and the baseline DAS28-CRP measurement as predictors in the model was performed.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2, 4, 8, 12, 18, and 24
    End point values
    ABP 501 Adalimumab
    Number of subjects analysed
    264 [3]
    262 [4]
    Units: units on a scale
    least squares mean (standard deviation)
        Week 2 (n = 254, 252)
    -1.01 ± 0.891
    -0.96 ± 0.89
        Week 4 (n = 255, 254)
    -1.45 ± 1.048
    -1.42 ± 0.979
        Week 8 (n = 247, 255)
    -1.79 ± 1.075
    -1.7 ± 1.093
        Week 12 (n = 245, 250)
    -2.04 ± 1.112
    -1.93 ± 1.171
        Week 18 (n = 244, 250)
    -2.3 ± 1.184
    -2.17 ± 1.189
        Week 24 (n = 243, 250)
    -2.32 ± 1.237
    -2.32 ± 1.209
    Notes
    [3] - Full analysis set with available data at each time point
    [4] - Full analysis set with available data at each time point
    No statistical analyses for this end point

    Secondary: Percentage of Participants with an ACR20 Response at Week 2 and Week 8

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    End point title
    Percentage of Participants with an ACR20 Response at Week 2 and Week 8
    End point description
    A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in tender joint count; • ≥ 20% improvement in swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Subject's assessment of pain (measured on a 100 mm VAS); ◦ Subject's Global Health Assessment (measured on a horizontal scale from 0 to 10); ◦ Investigator's Global Health Assessment (measured on a horizontal scale from 0 to 10); ◦ Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; ◦ C-reactive protein level.
    End point type
    Secondary
    End point timeframe
    Baseline and weeks 2 and 8
    End point values
    ABP 501 Adalimumab
    Number of subjects analysed
    264 [5]
    262 [6]
    Units: percentage of participants
    number (not applicable)
        Week 2 (n = 254, 257)
    35.4
    24.5
        Week 8 (n = 260, 261)
    63.5
    62.5
    Notes
    [5] - Full analysis set with LOCF
    [6] - Full analysis set with LOCF
    No statistical analyses for this end point

    Secondary: Percentage of Participants with an ACR50 Response at Week 24

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    End point title
    Percentage of Participants with an ACR50 Response at Week 24
    End point description
    A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in tender joint count; • ≥ 50% improvement in swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: ◦ Subject's assessment of pain (measured on a 100 mm VAS); ◦ Subject's Global Health Assessment (measured on a horizontal scale from 0 to 10); ◦ Investigator's Global Health Assessment (measured on a horizontal scale from 0 to 10); ◦ Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; ◦ C-reactive protein level.
    End point type
    Secondary
    End point timeframe
    Baseline and week 24
    End point values
    ABP 501 Adalimumab
    Number of subjects analysed
    244 [7]
    252 [8]
    Units: percentage of participants
        number (not applicable)
    49.2
    52
    Notes
    [7] - Full analysis set with available data
    [8] - Full analysis set with available data
    No statistical analyses for this end point

    Secondary: Percentage of Participants with an ACR70 Response at Week 24

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    End point title
    Percentage of Participants with an ACR70 Response at Week 24
    End point description
    A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in tender joint count; • ≥ 70% improvement in swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: ◦ Subject's assessment of pain (measured on a 100 mm VAS); ◦ Subject's Global Health Assessment (measured on a horizontal scale from 0 to 10); ◦ Investigator's Global Health Assessment (measured on a horizontal scale from 0 to 10); ◦ Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; ◦ C-reactive protein level.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 24
    End point values
    ABP 501 Adalimumab
    Number of subjects analysed
    246 [9]
    253 [10]
    Units: percentage of participants
        number (not applicable)
    26
    22.9
    Notes
    [9] - Full analysis set with available data
    [10] - Full analysis set with available data
    No statistical analyses for this end point

    Secondary: Number of Participants with Adverse Events

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    End point title
    Number of Participants with Adverse Events
    End point description
    Adverse events (AEs) were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 according to the following scale: 1 = mild; 2 = moderate; 3 = severe; 4 = life-threatening; 5 = fatal. A treatment-related AE is defined as an event where the answer to the question “is there a reasonable possibility that the event may have been caused by the Investigational Medicinal Product” was yes. A serious adverse event is defined as an AE that meets at least 1 of the following serious criteria: • fatal • life threatening (places the subject at immediate risk of death) • requires inpatient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • congenital anomaly/birth defect • other medically important serious event.
    End point type
    Secondary
    End point timeframe
    From the time of first treatment up to 28 days following the last dose of study treatment; 26 weeks.
    End point values
    ABP 501 Adalimumab
    Number of subjects analysed
    264
    262
    Units: participants
        Any adverse event
    132
    143
        Adverse event ≥ grade 3
    9
    17
        Treatment-related adverse event
    50
    56
        Treatment-related adverse event ≥ grade 3
    3
    2
        Serious adverse event
    10
    13
        AE leading to discontinuation of study drug
    5
    2
        TRAE leading to discontinuation of study drug
    4
    1
        AE leading to discontinuation from study
    7
    2
        TRAE leading to discontinuation from study
    5
    0
        Treatment-related serious adverse event
    4
    1
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Developed Antibodies to ABP 501 or Adalimumab

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    End point title
    Percentage of Participants Who Developed Antibodies to ABP 501 or Adalimumab
    End point description
    Two validated assays were used to detect the presence of anti-drug antibodies. Samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect anti-drug antibodies (ADA) against ABP 501 and adalimumab (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a non-cell based bioassay to determine neutralizing activity against ABP 501 or adalimumab (Neutralizing Antibody Assay). Developing antibody incidence is defined as a negative or no antibody result at baseline and a positive antibody result at a post-baseline time point.
    End point type
    Secondary
    End point timeframe
    Up to week 26
    End point values
    ABP 501 Adalimumab
    Number of subjects analysed
    264 [11]
    262 [12]
    Units: percentage of participants
    number (not applicable)
        Developing Binding Antibody
    38.3
    38.2
        Developing Neutralizing Antibody
    9.1
    11.1
    Notes
    [11] - Participants with at least 1 evaluable antibody test result (to either ABP 501 or adalimumab)
    [12] - Participants with at least 1 evaluable antibody test result (to either ABP 501 or adalimumab)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the time of first treatment but on or within 28 days following the last dose of study treatment; 26 weeks.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    ABP 501
    Reporting group description
    Participants received ABP 501 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.

    Reporting group title
    Adalimumab
    Reporting group description
    Participants received adalimumab 40 mg subcutaneously on day 1 and every 2 weeks thereafter until week 22.

    Serious adverse events
    ABP 501 Adalimumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 264 (3.79%)
    13 / 262 (4.96%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 264 (0.38%)
    0 / 262 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    1 / 264 (0.38%)
    0 / 262 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Humerus fracture
         subjects affected / exposed
    1 / 264 (0.38%)
    0 / 262 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    1 / 264 (0.38%)
    0 / 262 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 264 (0.00%)
    1 / 262 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 264 (0.00%)
    1 / 262 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 264 (0.00%)
    1 / 262 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    1 / 264 (0.38%)
    0 / 262 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 264 (0.00%)
    1 / 262 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wolff-Parkinson-White syndrome
         subjects affected / exposed
    0 / 264 (0.00%)
    1 / 262 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Corneal graft rejection
         subjects affected / exposed
    0 / 264 (0.00%)
    1 / 262 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypersensitivity
         subjects affected / exposed
    1 / 264 (0.38%)
    0 / 262 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    1 / 264 (0.38%)
    0 / 262 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 264 (0.38%)
    0 / 262 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Enterocolitis
         subjects affected / exposed
    1 / 264 (0.38%)
    0 / 262 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    0 / 264 (0.00%)
    1 / 262 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Foot deformity
         subjects affected / exposed
    0 / 264 (0.00%)
    1 / 262 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 264 (0.00%)
    1 / 262 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudarthrosis
         subjects affected / exposed
    0 / 264 (0.00%)
    1 / 262 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis perforated
         subjects affected / exposed
    1 / 264 (0.38%)
    0 / 262 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    0 / 264 (0.00%)
    1 / 262 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 264 (0.00%)
    1 / 262 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritoneal abscess
         subjects affected / exposed
    1 / 264 (0.38%)
    0 / 262 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 264 (0.38%)
    0 / 262 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia fungal
         subjects affected / exposed
    0 / 264 (0.00%)
    1 / 262 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 264 (0.76%)
    0 / 262 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    ABP 501 Adalimumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    17 / 264 (6.44%)
    19 / 262 (7.25%)
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    17 / 264 (6.44%)
    19 / 262 (7.25%)
         occurrences all number
    19
    21

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 Jun 2013
    • changed the primary endpoint to RR of ACR20 at week 24 (assuming an expected ACR20 response for both ABP 501 and adalimumab of 63% at week 24) between ABP 501 and adalimumab, with an equivalence margin of (0.738, 1/0.738) • changed the secondary efficacy criteria to the following: o DAS28-CRP change from baseline at weeks 2, 4, 8, 12, 18, and 24 o RR of ACR20 at weeks 2 and 8 o RR of ACR50 and ACR70 responses at week 24 • added efficacy assessments at weeks 2, 8, and 18 to support the secondary criteria • required study discontinuation in the case of pregnancy and removed the requirement for discontinuation for progressive disease • changed the Subject and Investigator Global Health Assessments to 0 to 10 horizontal scale (rather than VAS) and updated the description of the pain VAS to match the sample form

    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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