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    Clinical Trial Results:
    An Open-label Extension Study to Compare the Long-term Efficacy, Safety, Immunogenicity and Pharmacokinetics of FKB327 and Humira® in Patients with Rheumatoid Arthritis on Concomitant Methotrexate

    Summary
    EudraCT number
    2014-000110-61
    Trial protocol
    DE   CZ   ES  
    Global end of trial date
    28 Jan 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    03 Jan 2019
    First version publication date
    03 Jan 2019
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    FKB327-003
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02405780
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    FUJIFILM KYOWA KIRIN BIOLOGICS Co., Ltd.
    Sponsor organisation address
    1-6-1 Ohtemachi, Chiyoda-ku, Tokyo, Japan, 100-8185
    Public contact
    Clinical Trial Information, Fujifilm Kyowa Kirin Biologics Co., Ltd., EU Branch, +44 1896668173, Clinical-Trials@fk-b.com
    Scientific contact
    Clinical Trial Information, Fujifilm Kyowa Kirin Biologics Co., Ltd., EU Branch, +44 1896668173, Clinical-Trials@fk-b.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
    28 Jan 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Jan 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Jan 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Primary: • To compare the safety of long-term treatment with FKB327 and Humira in patients with rheumatoid arthritis (RA). Secondary: • To compare the efficacy of long term treatment with FKB327 and Humira. • To compare the proportions of RA patients developing anti-drug antibodies (ADAs) on long term treatment with FKB327 and Humira. • To compare the pharmacokinetics (PK) of long term treatment with FKB327 and Humira. • To evaluate safety, changes in efficacy, changes in PK and immunogenicity in patients switching from Humira in the preceding FKB327-002 double-blind study to FKB327 in the open label extension (OLE) study, and of patients who were switched from FKB327 to Humira, respectively. • To evaluate safety, changes in efficacy, changes in PK and immunogenicity in patients switching from FKB327 in the preceding FKB327-002 double-blind study to Humira in the OLE study, and then switched back to FKB327 in the second part of the OLE study (from Week 30; double switch).
    Protection of trial subjects
    The study was performed in compliance with the European Union (EU) Directives 2001/20/EC and 2015/28/EC and the Declaration of Helsinki (South Africa Revision 1996) Good Manufacturing Practice (GMP) and Good Clinical Practice. The study protocol, informed consent form, and amendments were reviewed and approved by each Independent Ethics Committee (IEC)/Institutional Review Board (IRB). The study did not start at a given investigational site before the IEC/IRB had given written approval or a favourable opinion. All subjects provided written informed consent before any study-specific procedures or assessments were performed. Subjects were free to refuse entry into the study and were free to withdraw from the study at any time without prejudice to future treatment.
    Background therapy
    FKB327 or Humira 40 mg every other week, as subjects were only eligible for entry to the study if they were currently participating in the double blind study FKB327-002. Methotrexate (MTX) represents the conventional disease modifying anti-rheumatic drug (DMARD) of choice for Rheumatoid Arthritis (RA) treatment and is thought to act by decreasing the activity of the immune system. MTX was administered with folate therapy to counter down the know adverse effects of MTX treatment. In line with clinical practice, stable background doses of oral steroids and non-steroidal anti-inflammatory drugs (NSAIDs) were permitted during the study although they were not compulsory.
    Evidence for comparator
    Adalimumab is a recombinant human monoclonal antibody against Tumor Necrosing Factor (TNF) α. It neutralises the biological activity of TNF- α by blocking its interaction with TNF- α cell surface receptors. TNF- α is a naturally occurring cytokine produced by many different cell types, including macrophages, mast cells and T-cells. High concentrations of TNF- α lead to inflammation and injury, and TNF- α has been implicated as an important pro-inflammatory cytokine involved in the parthenogenesis of numerous autoimmune diseases, such as RA, psoriasis (Ps), Crohn’s disease (CD) and ulcerative colitis (UC). Adalimumab was first approved for treatment of RA in September 2003 in the European Union (EU), and was subsequently launched globally under the brand name Humira. Humira is currently indicated in the EU in the adult population for RA, Ps, Psoriatic Arthritis (PsA), Ankylosing Spondylitis (AS) axial spondyloarthritis (without radiographic evidence of AS), CD, UC, hidradentis suppurativa (HS) and non-infectious uveitis. Approved indication in the paediatric population are polyarticular juvenile idiopathic arthritis in children from 2 years of age, active enthesitis-related arthritis from 6 years of age, severe chronic plaque psoriasis from 4 years of age, moderately to severe CD from 6 years of age and moderate to severe HS in adolescents from 12 years of age.
    Actual start date of recruitment
    01 Jun 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
    Poland: 124
    Country: Number of subjects enrolled
    Romania: 23
    Country: Number of subjects enrolled
    Spain: 9
    Country: Number of subjects enrolled
    Czech Republic: 64
    Country: Number of subjects enrolled
    Germany: 22
    Country: Number of subjects enrolled
    Chile: 40
    Country: Number of subjects enrolled
    Peru: 84
    Country: Number of subjects enrolled
    Russian Federation: 96
    Country: Number of subjects enrolled
    United States: 71
    Country: Number of subjects enrolled
    Canada: 5
    Country: Number of subjects enrolled
    Ukraine: 107
    Worldwide total number of subjects
    645
    EEA total number of subjects
    242
    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)
    540
    From 65 to 84 years
    103
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    The study was conducted at 92 sites, with 11 countries in Europe, North America, and Rest of World recruiting patients into the study. In total, 645 patients with RA who completed study FKB327-002 and, in the Investigator's opinion, showed a clinical response to treatment during FKB327-002 were screened and entered the FKB327-003 study.

    Pre-assignment
    Screening details
    Patients who received FKB327 in Study FKB327-002 were re-randomised to FKB327 or Humira in a 2:1 ratio and patients who received Humira in Study FKB327-002 were re-randomised to Humira or FKB327 in a 2:1 ratio.

    Period 1
    Period 1 title
    Period I
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded
    Blinding implementation details
    This was an open-label study throughout.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    FKB327-FKB327
    Arm description
    This arm included patients who were treated with FKB327 in the preceding Study FKB327-002 and were randomised to continue on FKB327 treatment during Period I in Study FKB327-003.
    Arm type
    Experimental

    Investigational medicinal product name
    adalimumab (FKB327)
    Investigational medicinal product code
    FKB327
    Other name
    Hulio
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    The dose administered was one (1) subcutaneous injection of 40 mg/0.8 mL every other week.

    Arm title
    Humira-FKB327
    Arm description
    This arm included patients who were treated with the reference product Humira in the preceding Study FKB327-002 and were randomised to FKB327 treatment during Period I in Study FKB327-003.
    Arm type
    Experimental

    Investigational medicinal product name
    adalimumab (FKB327)
    Investigational medicinal product code
    FKB327
    Other name
    Hulio
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    The dose administered was one (1) subcutaneous injection of 40 mg/0.8 mL every other week.

    Arm title
    FKB327-Humira
    Arm description
    This arm included patients who were treated with FKB327 in the preceding Study FKB327-002 and were randomised to the reference product Humira during Period I in Study FKB327-003.
    Arm type
    Active comparator

    Investigational medicinal product name
    adalimumab (Humira)
    Investigational medicinal product code
    Humira
    Other name
    Humira
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    The dose administered was one (1) subcutaneous injection of 40 mg/ 0.8 mL every other week.

    Arm title
    Humira-Humira
    Arm description
    This arm included patients who were treated with the reference product Humira in the preceding Study FKB327-002 and were randomised to continue on Humira during Period I in Study FKB327-003.
    Arm type
    Active comparator

    Investigational medicinal product name
    adalimumab (Humira)
    Investigational medicinal product code
    Humira
    Other name
    Humira
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    The dose administered was one (1) subcutaneous injection of 40 mg/0.8 mL every other week.

    Number of subjects in period 1
    FKB327-FKB327 Humira-FKB327 FKB327-Humira Humira-Humira
    Started
    216
    108
    108
    213
    Completed
    189
    93
    100
    190
    Not completed
    27
    15
    8
    23
         Protocol deviation
    8
    8
    6
    11
         Adverse event, serious fatal
    -
    1
    -
    1
         Adverse event, non-fatal
    8
    2
    -
    6
         Medical reason
    1
    -
    1
    1
         Consent withdrawn by subject
    9
    3
    1
    4
         Screening failure
    1
    1
    -
    -
    Period 2
    Period 2 title
    Period II
    Is this the baseline period?
    No
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    FKB327-FKB327-FKB327
    Arm description
    This treatment arm included patients that had been treated with FKB327 in the preceding study FKB327-002 and were continued on FKB327 in Period I of Study FKB327-003. At week 30, patients were transferred to continue on treatment with FKB327 (F-F-F) in Period II of Study FKB327-003.
    Arm type
    Experimental

    Investigational medicinal product name
    adalimumab (FKB327)
    Investigational medicinal product code
    FKB327
    Other name
    Hulio
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    The dose administered was one (1) subcutaneous injection of 40 mg/0.8 mL every other week using an auto-injector (pre-filled pen) or pre-filled syringe.

    Arm title
    Humira-FKB327-FKB327
    Arm description
    This treatment arm included patients that had been treated with the reference product in the preceding study FKB327-002 and were treated with FKB327 in Period I of Study FKB327-003. At week 30, patients were transferred to treatment with FKB327 (H-F-F) in Period II of Study FKB327-003.
    Arm type
    Experimental

    Investigational medicinal product name
    adalimumab (FKB327)
    Investigational medicinal product code
    FKB327
    Other name
    Hulio
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    The dose administered was one (1) subcutaneous injection of 40 mg/0.8 mL every other week using an auto-injector (pre-filled pen) or pre-filled syringe.

    Arm title
    FKB327-Humira-FKB327
    Arm description
    This treatment arm included patients that had been treated with FKB327 in the preceding study FKB327-002 and were treated with the reference product, Humira, in Period I of Study FKB327-003. At week 30, patients were transferred to treatment with FKB327 (F-H-F) in Period II of Study FKB327-003.
    Arm type
    Experimental

    Investigational medicinal product name
    adalimumab (FKB327)
    Investigational medicinal product code
    FKB327
    Other name
    Hulio
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    The dose administered was one (1) subcutaneous injection of 40 mg/0.8 mL every other week using an auto-injector (pre-filled pen) or pre-filled syringe.

    Arm title
    Humira-Humira-FKB327
    Arm description
    This treatment arm included patients that had been treated with the reference product Humira in the preceding study FKB327-002 and werecontinued on Humira in Period I of Study FKB327-003. At week 30, patients were transferred to treatment with FKB327 (H-H-F) in Period II of Study FKB327-003.
    Arm type
    Experimental

    Investigational medicinal product name
    adalimumab (FKB327)
    Investigational medicinal product code
    FKB327
    Other name
    Hulio
    Pharmaceutical forms
    Solution for injection in pre-filled pen
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    The dose administered was one (1) subcutaneous injection of 40 mg/0.8 mL every other week using an auto-injector (pre-filled pen) or pre-filled syringe.

    Number of subjects in period 2
    FKB327-FKB327-FKB327 Humira-FKB327-FKB327 FKB327-Humira-FKB327 Humira-Humira-FKB327
    Started
    189
    93
    100
    190
    Completed
    174
    81
    88
    172
    Not completed
    15
    12
    12
    18
         non-compliance with protocol
    5
    -
    -
    -
         Pregnancy
    -
    1
    -
    -
         Adverse event, serious fatal
    -
    2
    -
    1
         Adverse event, non-fatal
    3
    2
    5
    10
         non-compliance with study procedures
    -
    7
    2
    4
         Medical reason
    -
    -
    1
    -
         Consent withdrawn by subject
    7
    -
    4
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    FKB327-FKB327
    Reporting group description
    This arm included patients who were treated with FKB327 in the preceding Study FKB327-002 and were randomised to continue on FKB327 treatment during Period I in Study FKB327-003.

    Reporting group title
    Humira-FKB327
    Reporting group description
    This arm included patients who were treated with the reference product Humira in the preceding Study FKB327-002 and were randomised to FKB327 treatment during Period I in Study FKB327-003.

    Reporting group title
    FKB327-Humira
    Reporting group description
    This arm included patients who were treated with FKB327 in the preceding Study FKB327-002 and were randomised to the reference product Humira during Period I in Study FKB327-003.

    Reporting group title
    Humira-Humira
    Reporting group description
    This arm included patients who were treated with the reference product Humira in the preceding Study FKB327-002 and were randomised to continue on Humira during Period I in Study FKB327-003.

    Reporting group values
    FKB327-FKB327 Humira-FKB327 FKB327-Humira Humira-Humira Total
    Number of subjects
    216 108 108 213 645
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    183 96 92 169 540
        From 65-84 years
    32 12 16 43 103
        85 years and over
    1 0 0 1 2
    Gender categorical
    Units: Subjects
        Female
    162 83 85 171 501
        Male
    54 25 23 42 144
    Race
    Units: Subjects
        American Indian or Alaska Native
    1 0 0 1 2
        Asian
    1 1 0 0 2
        Black or African American
    1 2 1 2 6
        White
    187 90 90 185 552
        Other
    26 15 17 25 83
    Subject analysis sets

    Subject analysis set title
    Safety Analysis Set
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    The Safety Analysis Set comprised all patients who gave consent for this trial and who received at least 1 dose of randomised treatment. The Safety Analysis Set was used for all safety analyses.

    Subject analysis set title
    Full Analysis Set
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The Full Analysis Set (FAS) comprised all patients who received at least 1 dose of the randomised treatment and who had at least 1 evaluable efficacy measurement after their first does of randomised treatment. The FAS was used for all efficacy analysis.

    Subject analysis set title
    Pharmacokinetic Analysis Set
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    The Pharmacokinetic Analysis Set (PKAS) included all patients who received at least 1 dose of the randomised treatment and had at least 1 serum adalimumab concentration result after receiving randomised treatment in the FKB327-003 study.

    Subject analysis sets values
    Safety Analysis Set Full Analysis Set Pharmacokinetic Analysis Set
    Number of subjects
    645
    645
    630
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    540
    540
    530
        From 65-84 years
    103
    103
    98
        85 years and over
    2
    2
    2
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    Gender categorical
    Units: Subjects
        Female
    501
    501
    487
        Male
    144
    144
    143
    Race
    Units: Subjects
        American Indian or Alaska Native
    2
    2
    0
        Asian
    2
    2
    2
        Black or African American
    6
    6
    6
        White
    552
    552
    541
        Other
    83
    83
    81

    End points

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    End points reporting groups
    Reporting group title
    FKB327-FKB327
    Reporting group description
    This arm included patients who were treated with FKB327 in the preceding Study FKB327-002 and were randomised to continue on FKB327 treatment during Period I in Study FKB327-003.

    Reporting group title
    Humira-FKB327
    Reporting group description
    This arm included patients who were treated with the reference product Humira in the preceding Study FKB327-002 and were randomised to FKB327 treatment during Period I in Study FKB327-003.

    Reporting group title
    FKB327-Humira
    Reporting group description
    This arm included patients who were treated with FKB327 in the preceding Study FKB327-002 and were randomised to the reference product Humira during Period I in Study FKB327-003.

    Reporting group title
    Humira-Humira
    Reporting group description
    This arm included patients who were treated with the reference product Humira in the preceding Study FKB327-002 and were randomised to continue on Humira during Period I in Study FKB327-003.
    Reporting group title
    FKB327-FKB327-FKB327
    Reporting group description
    This treatment arm included patients that had been treated with FKB327 in the preceding study FKB327-002 and were continued on FKB327 in Period I of Study FKB327-003. At week 30, patients were transferred to continue on treatment with FKB327 (F-F-F) in Period II of Study FKB327-003.

    Reporting group title
    Humira-FKB327-FKB327
    Reporting group description
    This treatment arm included patients that had been treated with the reference product in the preceding study FKB327-002 and were treated with FKB327 in Period I of Study FKB327-003. At week 30, patients were transferred to treatment with FKB327 (H-F-F) in Period II of Study FKB327-003.

    Reporting group title
    FKB327-Humira-FKB327
    Reporting group description
    This treatment arm included patients that had been treated with FKB327 in the preceding study FKB327-002 and were treated with the reference product, Humira, in Period I of Study FKB327-003. At week 30, patients were transferred to treatment with FKB327 (F-H-F) in Period II of Study FKB327-003.

    Reporting group title
    Humira-Humira-FKB327
    Reporting group description
    This treatment arm included patients that had been treated with the reference product Humira in the preceding study FKB327-002 and werecontinued on Humira in Period I of Study FKB327-003. At week 30, patients were transferred to treatment with FKB327 (H-H-F) in Period II of Study FKB327-003.

    Subject analysis set title
    Safety Analysis Set
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    The Safety Analysis Set comprised all patients who gave consent for this trial and who received at least 1 dose of randomised treatment. The Safety Analysis Set was used for all safety analyses.

    Subject analysis set title
    Full Analysis Set
    Subject analysis set type
    Full analysis
    Subject analysis set description
    The Full Analysis Set (FAS) comprised all patients who received at least 1 dose of the randomised treatment and who had at least 1 evaluable efficacy measurement after their first does of randomised treatment. The FAS was used for all efficacy analysis.

    Subject analysis set title
    Pharmacokinetic Analysis Set
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    The Pharmacokinetic Analysis Set (PKAS) included all patients who received at least 1 dose of the randomised treatment and had at least 1 serum adalimumab concentration result after receiving randomised treatment in the FKB327-003 study.

    Primary: Safety - Summary of Adverse Events; Period I

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    End point title
    Safety - Summary of Adverse Events; Period I [1]
    End point description
    Each patient was counted only once within each System Organ Class (SOC) and Preferred Term (PT). A patients may have had multiple events counted. Death is defined as the fatal outcome of an (S) AE. Treatment Emergent Adverse Events (TEAE) defined as AEs that started or increased in severity after the first study medication administration and counted under the treatment arm in which they started.
    End point type
    Primary
    End point timeframe
    Period I: From Baseline visit week 0 through to week 30
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No formal statistical analysis is provided for this end point. Summary statistics only are presented.
    End point values
    FKB327-FKB327 Humira-FKB327 FKB327-Humira Humira-Humira Safety Analysis Set
    Number of subjects analysed
    216
    108
    108
    213
    645
    Units: number of patients
    number (not applicable)
        Deaths
    0
    1
    0
    1
    2
        Treatment Emergent Deaths
    0
    1
    0
    1
    2
        At least 1 TEAE
    103
    59
    59
    117
    338
        At least 1 severe TEAE
    5
    3
    2
    2
    12
        At least 1 treatment related TEAE
    39
    27
    21
    49
    136
        Premature disc. of treatment due to a TEAE
    10
    4
    0
    11
    25
        Treatment Disc. due to a TESAE
    0
    0
    0
    2
    2
        Treatment interruption due to a TEAE
    19
    14
    9
    20
    62
        Treatment interruption due to a TESAE
    3
    4
    2
    2
    11
        At least 1 TESAE
    5
    5
    7
    7
    24
        Number of TESAE
    7
    9
    9
    7
    32
        At leaset 1 SAE
    5
    5
    7
    7
    24
    No statistical analyses for this end point

    Primary: Vital signs

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    End point title
    Vital signs [2]
    End point description
    Vital signs = blood pressure, pulse and temperature measurements forms part of the continuous safety measurements for the study primary safety endpoint. Blood pressure and pulse rate were measured prior to dosing after the patient had rested in a supine or semi-recumbent position for at least 5 minutes. Vital signs parameters with change from Baseline_002 were summarised by treatment sequence over the whole study period as well as by treatment for each period (Period I and Period II) for each visit. Baseline_002 is defined as the last non-missing measurement collected prior to the first study medication administration at Week 0 from FKB327-002. RESULTS: There were no trends in changes from Baseline/Week 0 for any of the vital signs parameters. TEAEs related to changes in vital signs parameters occurred in a small number of patients, with hypertension/increased blood pressure being the most commonly reported event.
    End point type
    Primary
    End point timeframe
    Weeks 0, 4, 8, 12, 24 and 80/EOT (Period I and II)
    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: No formal statistical analysis is provided for this end point. Summary statistics only are presented.
    End point values
    Safety Analysis Set
    Number of subjects analysed
    645
    Units: various
    645
    No statistical analyses for this end point

    Primary: Clinical Laboratory Tests

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    End point title
    Clinical Laboratory Tests [3]
    End point description
    RESULTS: There were no clinically relevant changes from Baseline/Week 0 in mean values for any of the haematology, biochemistry or urinalysis parameters. Although there were increases and/or decreases in mean values for several of the laboratory parameters throughout the study, but no clear pattern and the changes were comparable on treatment with FKB327 and Humira. The most commonly reported laboratory-related TEAE was anaemia, which was experienced by 5 patients receiving FKB327 and 4 patients receiving Humira during Period I and by a further 11 patients receiving FKB327 during Period II. Commonly reported TEAEs related to liver function test abnormalities were experienced by a similar incidence of patients receiving FKB327 and Humira during Period I. Neutropaenia and leukopenia were both experienced by 3 patients receiving FKB327 and 1 patient receiving Humira during Period I.
    End point type
    Primary
    End point timeframe
    Weeks 0, 4, 8, 12, 24, 30 (Period I) and weeks 42, 54, 66, 76 and 80/EOT (Period II).
    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: No formal statistical analysis is provided for this end point. Summary statistics only are presented.
    End point values
    Safety Analysis Set
    Number of subjects analysed
    645
    Units: various
    645
    No statistical analyses for this end point

    Secondary: ACR20; Summary of Response rate over time: Period I

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    End point title
    ACR20; Summary of Response rate over time: Period I
    End point description
    The ACR response criteria was derived and used as secondary efficacy variables. These criteria look at improvement in tender joint count (TJC), swollen joint count (SJC) (68/66-joint count) and improvement in at least 3 of the following 5 other specified ACR Core Data Set elements: - Acute phase reactant (CRP). - Patient global assessment of disease activity. - Physician global assessment of disease activity. - Patient pain scale (VAS). - Disability/functional questionnaire (patient completed Health Assessment Questionnaire -Disability Index (HAQ-DI)) An ACR20 positive response means that the patient achieved a 20% improvement in tender and swollen joint counts and a 20% improvement in at least 3 of the other 5 Core Data Set elements listed above.
    End point type
    Secondary
    End point timeframe
    Weeks 0, 4, 8, 12 and 24 (Period I)
    End point values
    FKB327-FKB327 Humira-FKB327 FKB327-Humira Humira-Humira Full Analysis Set
    Number of subjects analysed
    216 [4]
    108 [5]
    108 [6]
    212 [7]
    644 [8]
    Units: percentage of participants
    number (confidence interval 95%)
        week 0
    75.5 (69.2 to 81.0)
    75.9 (66.7 to 83.6)
    80.6 (71.8 to 87.5)
    82.5 (76.8 to 87.4)
    78.7 (75.4 to 81.8)
        week 4
    81.4 (75.5 to 86.4)
    78.5 (69.5 to 85.9)
    79.0 (70.0 to 86.4)
    79.3 (73.2 to 84.6)
    79.8 (76.5 to 82.9)
        week 8
    78.0 (71.8 to 83.5)
    76.0 (66.6 to 83.8)
    81.6 (72.7 to 88.5)
    84.8 (79.1 to 89.4)
    80.5 (77.2 to 83.6)
        week 12
    78.8 (72.5 to 84.2)
    79.6 (70.5 to 86.9)
    87.3 (79.2 to 93.0)
    84.2 (78.5 to 89.0)
    82.2 (78.9 to 85.1)
        week 24
    82.2 (76.2 to 87.3)
    78.9 (69.4 to 86.6)
    83.0 (74.2 to 89.8)
    88.9 (83.7 to 92.9)
    84.1 (80.9 to 86.9)
    Notes
    [4] - subjects analysed at w 4 - 210; w 8 - 205; w 12 - 203; w 24 - 197
    [5] - subjects analysed at w 4 - 107; w 8 - 104; w 12 - 103; w 24 - 95
    [6] - subjects analysed at w 4 - 105; w 8 - 103; w 12 - 102; w 24 - 100
    [7] - subjects analysed at w 4 - 208; w 8 - 204; w 12 - 203 - w 24 - 198
    [8] - subjects analysed at w 4 - 630; w 8 - 616; w 12 - 611; w 24 - 590
    No statistical analyses for this end point

    Secondary: ACR20; Summary of Response rate over time: Period II

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    End point title
    ACR20; Summary of Response rate over time: Period II
    End point description
    In period II all patients received FKB327. Long-term efficacy was evaluated up to week 80 and efficacy was evaluated for patients who switched treatment from FKB327 or Humira in Study FKB327-002 to Humira in Study FKB327-003 and back to FKB327 in Period II. The ACR20 response criteria over time is defined as a 20% improvement in tender joint count, swollen joint count (68/66 joint count) and improvement in at least 3 of the following 5 other specified ACR Core Data Set elements from Baseline (Week 0 of study FKB327-002): • Acute phase reactant (CRP). • Patient global assessment of disease activity. • Physician global assessment of disease activity. • Patient pain scale. • Disability/functional questionnaire (patient completed HAQ-DI)
    End point type
    Secondary
    End point timeframe
    Weeks 30, 42, 54, 66, 76, and 80 (Period II)
    End point values
    FKB327-FKB327-FKB327 Humira-FKB327-FKB327 FKB327-Humira-FKB327 Humira-Humira-FKB327 Full Analysis Set
    Number of subjects analysed
    185 [9]
    92 [10]
    98 [11]
    189 [12]
    564 [13]
    Units: percentage of participants
    number (confidence interval 100%)
        week 30
    83.2 (77.1 to 88.3)
    85.9 (77.0 to 92.3)
    83.7 (74.8 to 90.4)
    83.6 (77.5 to 88.6)
    83.9 (80.6 to 86.8)
        week 42
    84.8 (78.8 to 89.6)
    90.0 (81.9 to 95.3)
    82.3 (73.2 to 89.3)
    87.7 (82.1 to 92.0)
    86.2 (83.0 to 88.9)
        week 54
    82.8 (76.5 to 88.0)
    85.6 (76.6 to 92.1)
    83.9 (74.8 to 90.7)
    84.4 (78.3 to 89.4)
    84.0 (80.6 to 87.0)
        week 66
    80.5 (73.8 to 86.1)
    88.1 (79.2 to 94.1)
    82.0 (72.5 to 89.4)
    85.7 (79.6 to 90.5)
    83.7 (80.3 to 86.8)
        week 76
    80.0 (73.3 to 85.7)
    87.7 (78.5 to 93.9)
    85.6 (76.6 to 92.1)
    85.5 (79.3 to 90.4)
    84.0 (80.5 to 87.0)
        week 80
    76.9 (69.9 to 82.9)
    76.5 (65.8 to 85.2)
    81.8 (72.2 to 89.2)
    82.4 (75.8 to 87.8)
    79.5 (75.7 to 82.9)
    Notes
    [9] - subjects analysed at w 42 - 184; w 54 - 180; w 66 - 174 - w 76 - 175; w 80 - 173
    [10] - subjects analysed at w 42 - 90; w 54 - 90; w 66 - 84; w 76 - 81; w 80 - 81
    [11] - subjects analysed at w 42 - 96; w 54 - 93; w 66 - 89; w 76 - 90; w 80 - 88
    [12] - subjects analysed at w 42 - 187; w 54 - 180; w 66 - 175; w 76 - 172; w 80 - 170
    [13] - subjects analysed at w 42- 557; w 54 - 543; w 66 - 522; w 76 - 518; w 80 - 512
    No statistical analyses for this end point

    Secondary: ACR50 Summary of response rate over time: Period I

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    End point title
    ACR50 Summary of response rate over time: Period I
    End point description
    The ACR50 response criteria over time is defined as a 50% improvement in tender joint count, swollen joint count (68/66 joint count) and improvement in at least 3 of the following 5 other specified ACR Core Data Set elements from Baseline (Week 0 of study FKB327-002): • Acute phase reactant (CRP). • Patient global assessment of disease activity. • Physician global assessment of disease activity. • Patient pain scale. • Disability/functional questionnaire (patient completed HAQ-DI)
    End point type
    Secondary
    End point timeframe
    Weeks 0, 4, 8, 12 and 24 (Period I)
    End point values
    FKB327-FKB327 Humira-FKB327 FKB327-Humira Humira-Humira Full Analysis Set
    Number of subjects analysed
    215 [14]
    108 [15]
    108 [16]
    212 [17]
    643 [18]
    Units: percentage of patients
    number (confidence interval 100%)
        week 0
    48.4 (41.5 to 55.3)
    46.3 (36.7 to 56.2)
    48.1 (38.4 to 58.0)
    51.4 (44.5 to 58.3)
    49.0 (45.1 to 52.9)
        week 4
    52.1 (45.2 to 59.0)
    48.6 (38.8 to 58.5)
    47.6 (37.8 to 57.6)
    55.3 (48.3 to 62.2)
    51.8 (47.8 to 55.8)
        week 8
    51.7 (44.6 to 58.7)
    49.0 (39.1 to 59.0)
    51.5 (41.4 to 61.4)
    60.8 (53.7 to 67.5)
    54.2 (50.2 to 58.2)
        week 12
    52.5 (45.3 to 59.5)
    53.4 (43.3 to 63.3)
    52.0 (41.8 to 62.0)
    64.5 (57.5 to 71.1)
    56.6 (52.5 to 60.5)
        week 24
    57.9 (50.6 to 64.9)
    51.6 (41.1 to 62.0)
    56.0 (45.7 to 65.9)
    63.8 (56.7 to 70.5)
    58.5 (54.5 to 62.5)
    Notes
    [14] - subjects analysed at week 4 - 211; w 8 - 205; w 12 - 202; w 24 - 197
    [15] - subjects analysed at week 4 - 107; w 8 - 104; w 12 - 103; w 24 - 95
    [16] - subjects analysed at week 4 - 105; w 8 - 103; w 12 - 102; w 24 - 100
    [17] - subjects analysed at week 4 - 208; w 8 - 204; w 12 - 203; w 24 - 199
    [18] - Subjects analysed at week 4 - 631; w 8 - 616; w 12 - 610; w 24 - 591
    No statistical analyses for this end point

    Secondary: ACR50 Summary of response rate over time: Period II

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    End point title
    ACR50 Summary of response rate over time: Period II
    End point description
    The ACR50 response criteria over time is defined as a 50% improvement in tender joint count, swollen joint count (68/66 joint count) and improvement in at least 3 of the following 5 other specified ACR Core Data Set elements from Baseline (Week 0 of study FKB327-002): • Acute phase reactant (CRP). • Patient global assessment of disease activity. • Physician global assessment of disease activity. • Patient pain scale. • Disability/functional questionnaire (patient completed HAQ-DI)
    End point type
    Secondary
    End point timeframe
    Weeks 30, 42, 54, 66, 76 and 80 (Period II)
    End point values
    FKB327-FKB327-FKB327 Humira-FKB327-FKB327 FKB327-Humira-FKB327 Humira-Humira-FKB327 Full Analysis Set
    Number of subjects analysed
    185 [19]
    92 [20]
    98 [21]
    189 [22]
    564 [23]
    Units: percentage of patients
    number (confidence interval 100%)
        Week 30
    60.5 (53.1 to 67.6)
    54.3 (43.6 to 64.8)
    58.2 (47.8 to 68.1)
    59.8 (52.4 to 66.8)
    58.9 (54.7 to 63.0)
        Week 42
    61.4 (54.0 to 68.5)
    60.0 (49.1 to 70.2)
    49.0 (38.6 to 59.4)
    61.5 (54.1 to 68.5)
    59.1 (54.9 to 63.2)
        Week 54
    58.9 (51.3 to 66.2)
    48.9 (38.2 to 59.7)
    51.1 (40.4 to 61.7)
    61.1 (53.6 to 68.3)
    56.6 (52.4 to 60.9)
        Week 66
    63.2 (55.6 to 70.4)
    54.8 (43.5 to 65.7)
    53.9 (43.0 to 64.6)
    65.1 (57.6 to 72.2)
    60.9 (56.6 to 65.1)
        Week76
    61.7 (54.1 to 68.9)
    53.1 (41.7 to 64.3)
    65.6 (54.8 to 75.3)
    62.4 (54.8 to 69.7)
    61.3 (56.9 to 65.5)
        Week 80
    59.0 (51.2 to 66.4)
    53.1 (41.7 to 64.3)
    53.4 (42.5 to 64.1)
    65.9 (58.2 to 73.0)
    59.4 (55.0 to 63.7)
    Notes
    [19] - subjects analysed at week 42 - 184; w 54 - 180; w 66 - 174; w 76 - 175; w 80 - 173
    [20] - subjects analysed at week 42 - 90; w 54 - 90; w 66 - 84; w 76 - 81 - w 80 - 81
    [21] - subjects analysed at week 42 - 96; w 54 - 92; w 66 - 89; w 76 - 90; w 80 - 88
    [22] - subjects analysed at week 42 - 187; w 54 - 180; w 66 - 175; w 76 -173; w 80 - 170
    [23] - subjects analysed at week 42 - 557; w 54 - 542; w 66 - 522; w 76 - 519; w 80 - 512
    No statistical analyses for this end point

    Secondary: ACR70 Summary of response rate over time: Period I

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    End point title
    ACR70 Summary of response rate over time: Period I
    End point description
    The ACR70 response criteria over time is defined as a 70% improvement in tender joint count, swollen joint count (68/66 joint count) and improvement in at least 3 of the following 5 other specified ACR Core Data Set elements from Baseline (Week 0 of study FKB327-002): • Acute phase reactant (CRP). • Patient global assessment of disease activity. • Physician global assessment of disease activity. • Patient pain scale. • Disability/functional questionnaire (patient completed HAQ-DI)
    End point type
    Secondary
    End point timeframe
    Weeks 0, 4, 8, 12, and 24 (Period I)
    End point values
    FKB327-FKB327 Humira-FKB327 FKB327-Humira Humira-Humira Full Analysis Set
    Number of subjects analysed
    216 [24]
    108 [25]
    108 [26]
    212 [27]
    644 [28]
    Units: percentage of patients
    number (confidence interval 100%)
        Week 0
    20.8 (15.6 to 26.9)
    21.3 (14.0 to 30.2)
    21.3 (14.0 to 30.2)
    26.4 (20.6 to 32.9)
    22.8 (19.6 to 26.3)
        Week 4
    25.6 (19.8 to 32.0)
    27.1 (19.0 to 36.6)
    28.8 (20.4 to 38.6)
    26.1 (20.2 to 32.6)
    26.6 (23.1 to 30.2)
        Week 8
    29.9 (23.7 to 36.7)
    25.0 (17.0 to 34.4)
    28.2 (19.7 to 37.9)
    35.3 (28.7 to 42.3)
    30.6 (26.9 to 34.4)
        Week 12
    29.1 (22.9 to 35.8)
    28.2 (19.7 to 37.9)
    27.5 (19.1 to 37.2)
    34.0 (27.5 to 41.0)
    30.3 (26.7 to 34.1)
        Week 24
    33.0 (26.5 to 40.0)
    26.3 (17.8 to 36.4)
    30.3 (21.5 to 40.4)
    40.2 (33.3 to 47.4)
    33.9 (30.1 to 37.9)
    Notes
    [24] - subjects analysed at week 4 - 211; w 8 - 204; w 12 - 203; w 24 - 197
    [25] - subjects analysed at week 4 - 107; w 8 - 104; w 12 - 103; w 24 - 95
    [26] - subjects analysed at week 4 - 104; w 8 - 103; w 12 - 102; w 24 - 99
    [27] - subjects analysed at week 4 - 207; w 8 - 204; w 12 - 203; w 24 - 199
    [28] - subjects analysed at week 4 - 629; w 8 - 615; w 12 - 611; w 24 - 590
    No statistical analyses for this end point

    Secondary: ACR70 Summary of response rate over time: Period II

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    End point title
    ACR70 Summary of response rate over time: Period II
    End point description
    The ACR70 response criteria over time is defined as a 70% improvement in tender joint count, swollen joint count (68/66 joint count) and improvement in at least 3 of the following 5 other specified ACR Core Data Set elements from Baseline (Week 0 of study FKB327-002): • Acute phase reactant (CRP). • Patient global assessment of disease activity. • Physician global assessment of disease activity. • Patient pain scale. • Disability/functional questionnaire (patient completed HAQ-DI)
    End point type
    Secondary
    End point timeframe
    Weeks 30, 42, 54, 66, 76 and 80 (Period II)
    End point values
    FKB327-FKB327-FKB327 Humira-FKB327-FKB327 FKB327-Humira-FKB327 Humira-Humira-FKB327 Full Analysis Set
    Number of subjects analysed
    185 [29]
    92 [30]
    99 [31]
    189 [32]
    565 [33]
    Units: percentage of patients
    number (confidence interval 100%)
        Week 30
    36.2 (29.3 to 43.6)
    30.4 (21.3 to 40.9)
    33.3 (24.2 to 43.5)
    39.2 (32.2 to 46.5)
    35.8 (31.8 to 39.9)
        Week 42
    39.1 (32.0 to 46.6)
    28.9 (19.8 to 39.4)
    28.1 (19.4 to 38.2)
    39.6 (32.5 to 47.0)
    35.7 (31.7 to 39.9)
        Week 54
    38.3 (31.2 to 45.9)
    21.1 (13.2 to 31.0)
    31.2 (22.0 to 41.6)
    38.3 (31.2 to 45.9)
    34.3 (30.3 to 38.4)
        Week 66
    39.7 (32.3 to 47.3)
    29.8 (20.3 to 40.7)
    32.6 (23.0 to 43.3)
    41.7 (34.3 to 49.4)
    37.5 (33.4 to 41.9)
        Week 76
    41.1 (33.8 to 48.8)
    24.7 (15.8 to 35.5)
    34.4 (24.7 to 45.2)
    41.0 (33.6 to 48.8)
    37.4 (33.2 to 41.7)
        Week 80
    37.2 (30.0 to 44.9)
    30.9 (21.1 to 42.1)
    30.7 (21.3 to 41.4)
    40.6 (33.1 to 48.4)
    36.2 (32.0 to 40.5)
    Notes
    [29] - subjects analysed at week 42 - 184; w 54 - 180; w 66 - 174; w 76 - 175; w 80 - 172
    [30] - subjects analysed at week 42 - 90; w 54 - 90; w 66 - 84; w 76 - 81; w 80 -81
    [31] - Subjects analysed at week 42 - 96; w 54 - 93; w 66 - 89; w 76 - 90; w 80 - 88
    [32] - subjects analysed at week 42 - 187; w 54 - 180; w 66 - 175; w 76 - 173; w 80 - 170
    [33] - subjects analysed at week 42 - 557; w 54 - 543; w 66 - 522; w 76 - 519; w 80 - 511
    No statistical analyses for this end point

    Secondary: DAS28-CRP Summary and changes over time: Period I

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    End point title
    DAS28-CRP Summary and changes over time: Period I
    End point description
    Changes over time in Disease Activity Score 28- C-reactive Protein (DAS28-CRP) compared to Baseline week 0 in Study FKB327-002: DAS28-CRP assessment involved evaluating 28 predefined tender and 28 predefined swollen joints, serum CRP, and global assessment of disease activity (VAS from 0 [very well] to 100 [extremely bad]). The DAS28-CRP is a number on a scale from 0 to 10 indicating the current activity of the patient's RA.
    End point type
    Secondary
    End point timeframe
    Weeks 0, 4, 8, 12 and 24 (Period I) and changes from Baseline in Study FKB327-002 at week 0, 4, 8, 12 and 24 (Period I).
    End point values
    FKB327-FKB327 Humira-FKB327 FKB327-Humira Humira-Humira
    Number of subjects analysed
    216 [34]
    108 [35]
    108 [36]
    213 [37]
    Units: units on a scale
    arithmetic mean (full range (min-max))
        Baseline_002
    6.02 (3.3 to 8.1)
    5.99 (3.7 to 7.9)
    6.12 (2.9 to 8.5)
    6.11 (4.0 to 8.0)
        Week 0
    3.46 (1.2 to 7.3)
    3.65 (1.2 to 7.2)
    3.49 (1.2 to 7.4)
    3.36 (1.2 to 7.0)
        Week 0 change from Baseline
    -2.56 (-5.7 to 1.0)
    -2.33 (-5.4 to 0.9)
    -2.63 (-6.4 to 1.2)
    -2.75 (-5.7 to 1.3)
        Week 4
    3.33 (1.2 to 7.0)
    3.53 (1.3 to 6.7)
    3.37 (1.2 to 7)
    3.29 (1.2 to 7.6)
        Week 4 change from Baseline
    -2.64 (-6.1 to 1.8)
    -2.48 (-4.9 to 1.6)
    -2.76 (-6.9 to 0.9)
    -2.81 (-6.1 to 1.8)
        Week 8
    3.28 (1.2 to 7.2)
    3.51 (1.2 to 6.6)
    3.37 (1.2 to 6.9)
    3.25 (1.2 to 7.1)
        Week 8 change from Baseline
    -2.72 (-5.9 to 2.7)
    -2.47 (-4.8 to 0.9)
    -2.74 (-6.9 to 0.8)
    -2.84 (-5.8 to 0.2)
        Week 12
    3.31 (1.2 to 6.9)
    3.40 (1.3 to 6.2)
    3.30 (1.2 to 7.1)
    3.21 (1.2 to 6.5)
        Week 12 change from Baseline
    -2.70 (-5.9 to 0.8)
    -2.57 (-4.9 to 0.5)
    -2.80 (-6.9 to 0.3)
    -2.88 (-5.8 to 0.9)
        Week 24
    3.13 (1.2 to 7.8)
    3.40 (1.2 to 7.7)
    3.27 (1.2 to 7.1)
    3.07 (1.2 to 7.5)
        Week 24 change from Baseline
    -2.89 (-6.1 to 1.3)
    -2.57 (-5.4 to 1.7)
    -2.86 (-6.7 to 0.9)
    -3.04 (-6.0 to -0.0)
    Notes
    [34] - Baseline_002 number of patients n=215
    [35] - Baseline_002 number of patients n=108
    [36] - Baseline_002 number of patients n=107
    [37] - Baseline_002 number of patients n=213
    No statistical analyses for this end point

    Secondary: DAS28-CRP Summary over time: Period II

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    End point title
    DAS28-CRP Summary over time: Period II
    End point description
    Changes over time in Disease Activity Score 28- C-reactive Protein (DAS28-CRP) compared to Baseline week 0 in Study FKB327-002 presented per treatment sequence and summarized for FKB327. During Period II, mean DAS28-CRP decreased from week 30 to week 76. A slight increase in DAS28-CRP was seen at week 80, possibly due to stopping treatment at week 76, but values remained below Baseline values. DAS28-CRP assessment involved evaluating 28 predefined tender and 28 predefined swollen joints, serum CRP, and global assessment of disease activity (VAS from 0 [very well] to 100 [extremely bad]). The DAS28-CRP is a number on a scale from 0 to 10 indicating the current activity of the patient's RA.
    End point type
    Secondary
    End point timeframe
    Weeks 30, 42, 54, 66, 76 and 80 and changes from Baseline in Study FKB327-002 at weeks 30, 42, 54, 66, 76 and 80 (Period II)
    End point values
    FKB327-FKB327-FKB327 Humira-FKB327-FKB327 FKB327-Humira-FKB327 Humira-Humira-FKB327 Full Analysis Set
    Number of subjects analysed
    183
    92
    99
    189
    563
    Units: units on a scale
    arithmetic mean (full range (min-max))
        Week 30
    3.04 (1.2 to 7.1)
    3.20 (1.3 to 6.3)
    3.28 (1.2 to 7.1)
    3.13 (1.2 to 7.4)
    3.14 (1.2 to 7.4)
        Week 30 Change from Baseline_002
    -2.99 (-6.1 to 0.3)
    -2.78 (-5.3 to 0.4)
    -2.84 (-6.6 to 0.5)
    -2.95 (-6.2 to 1.9)
    -2.92 (-6.6 to 1.9)
        Week 42
    3.05 (1.2 to 6.8)
    3.08 (1.3 to 6.0)
    3.28 (1.2 to 6.1)
    3.07 (1.2 to 7.3)
    3.10 (1.2 to 7.3)
        Week 42 Change from Baseline_002
    -2.97 (-5.6 to 0.9)
    -2.88 (-5.5 to -0.0)
    -2.83 (-6.2 to -0.2)
    -3.01 (-5.8 to 0.6)
    -2.95 (-6.2 to 0.9)
        Week 54
    3.04 (1.2 to 7.5)
    3.26 (1.2 to 6.2)
    3.22 (1.2 to 6.2)
    2.96 (1.2 to 6.8)
    3.08 (1.2 to 7.5)
        Week 54 Change from Baselin_002
    -2.99 (-5.9 to 0.4)
    -2.70 (-5.4 to 0.4)
    -2.90 (-6.2 to 0.9)
    -3.12 (-5.6 to 1.6)
    -2.97 (-6.2 to 1.6)
        Week 66
    2.96 (1.2 to 7.0)
    3.09 (1.3 to 5.6)
    3.17 (1.2 to 5.7)
    2.91 (1.2 to 6.9)
    3.00 (1.2 to 7.0)
        Week 66 Change from Baseline_002
    -3.09 (-5.9 to 0.3)
    -2.83 (-5.5 to 0.8)
    -2.96 (-6.9 to -0.0)
    -3.15 (-5.6 to 0.2)
    -3.05 (-6.9 to 0.8)
        Week 76
    2.97 (1.2 to 7.8)
    3.12 (1.3 to 7.0)
    3.02 (1.2 to 6.2)
    2.94 (1.2 to 6.4)
    2.99 (1.2 to 7.8)
        Week 76 Change from Baseline_002
    -3.04 (-5.9 to 0.2)
    -2.79 (-5.5 to 1.0)
    -3.11 (-6.1 to 0.4)
    -3.14 (-5.7 to -0.2)
    -3.04 (-6.1 to 1.0)
        Week 80
    2.98 (1.2 to 7.1)
    3.25 (1.2 to 6.7)
    3.09 (1.2 to 6.9)
    3.06 (1.2 to 6.7)
    3.07 (1.2 to 7.1)
        Week 80 Change from Baseline_002
    -3.05 (-6.2 to 2.2)
    -2.66 (-5.4 to 0.2)
    -3.05 (-6.9 to -0.3)
    -3.02 (-5.8 to 0.2)
    -2.98 (-6.9 to 2.2)
    No statistical analyses for this end point

    Secondary: Serum Concentration to Compare Treatment Across: Period I

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    End point title
    Serum Concentration to Compare Treatment Across: Period I
    End point description
    Repeated Measures model fitted to log-transformed PK trough concentrations at Weeks 12, 24 and 30 with fixed effect terms for week, treatment group and week × treatment group. Covariance structure: unstructured. Since the treatment * week interaction effect was found to be not significant at the 10% level (p-value = 0.4640) only the estimates across all time-points are displayed. - could not figure out how to present this Table 11.14 Mean serum drug concentrations at Week 0 were higher in the sequence groups that had been administered FKB327 in the previous study (ie, F-F and F-H). The inter-individual variability in systemic exposure was high throughout Period I, with CV ranging from 60.7% to 89.6%, across the treatment sequences. Mean serum drug concentration appeared generally stable between Week 0 to Week 30 for patients in the F-F, H-F and H-H treatment sequences, whilst a slight downward trend was observed for patients in the F-H treatment sequence.
    End point type
    Secondary
    End point timeframe
    PK-serum concentrations at weeks 0, 12, 24 and 30 (Period I)
    End point values
    FKB327-FKB327 Humira-FKB327 FKB327-Humira Humira-Humira
    Number of subjects analysed
    208
    107
    105
    210
    Units: ng/mL
    least squares mean (confidence interval 95%)
        Average over all time points
    4235.0 (3656.7 to 4904.7)
    4735.2 (3849.1 to 5825.3)
    3399.4 (2767.2 to 4176.0)
    4521.5 (3904.9 to 5235.4)
    No statistical analyses for this end point

    Secondary: ADA comparison and summary of status: Period I

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    End point title
    ADA comparison and summary of status: Period I
    End point description
    Blood samples for assessment of ADA activity were collected from Baseline week 0 to last sampling day. The proportion of patients with positive ADA status was highest prior to dosing at Week 0 (Baseline). The proportion of patients with positive ADA status decreased over time to Week 30 and was similar for both FKB327 and Humira at all timepoints.
    End point type
    Secondary
    End point timeframe
    Weeks 0, 12, 24 and 30 (Period I)
    End point values
    FKB327-FKB327 Humira-FKB327 FKB327-Humira Humira-Humira
    Number of subjects analysed
    216
    108
    108
    213
    Units: percentage of positive
    number (not applicable)
        Week 0
    61.6
    62.0
    63.9
    58.0
        Week 12
    53.0
    52.4
    58.3
    50.0
        Week 24
    50.3
    49.0
    58.0
    50.3
        Week 30
    51.9
    45.2
    61.0
    51.6
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Patients were carefully monitored for AEs from signing of informed consent until week 80 for patients who completed the study. For patients who discontinued the study early, a follow-up period of 4 weeks was added from the Early Termination Visit.
    Adverse event reporting additional description
    SAEs were followed until resolution, the investigator confirmed the event was unlikely to resolve or the patient was recorded as lost to follow-up.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    FKB327-FKB327
    Reporting group description
    This arm included patients who were treated with FKB327 in the preceding Study FKB327-002 and were randomised to continue on FKB327 treatment during Period I of Study FKB327-003.

    Reporting group title
    FKB327-Humira
    Reporting group description
    This arm included patients who were treated with FKB327 in the preceding Study FKB327-002 and were randomised to the reference product Humira during Period I of Study FKB327-003.

    Reporting group title
    Humira-FKB327
    Reporting group description
    This arm included patients who were treated with the reference product Humira in the preceding Study FKB327-002 and were randomised to FKB327 treatment during Period I of Study FKB327-003.

    Reporting group title
    Humira-Humira
    Reporting group description
    This arm included patients who were treated with the reference product Humira in the preceding Study FKB327-002 and were randomised to contiune on Humira during Period I of Study FKB327-003.

    Reporting group title
    FKB327-FKB327-FKB327
    Reporting group description
    This treatment arm included patients that had been treated with FKB327 in the preceding study, FKB327-002 and were re-randomised to continue on FKB327 in Period I of FKB327-003 study. At week 30 all patients were transferred to treatment with FKB327. (Period II)

    Reporting group title
    FKB327-Humira-FKB327
    Reporting group description
    This treatment arm included patients that had been treated with FKB327 in the preceding study, FKB327-002 and were randomised to the reference product Humira in Period I of FKB327-003 study. At week 30 all patients were transferred to treatment with FKB327. (Period II)

    Reporting group title
    Humira-FKB327-FKB327
    Reporting group description
    This treatment arm included patients that had been treated with the reference product Humira in the preceding study, FKB327-002 and were randomised to FKB327 in Period I of FKB327-003 study. At week 30 all patients were transferred to treatment with FKB327. (Period II)

    Reporting group title
    Humira-Humira-FKB327
    Reporting group description
    This treatment arm included patients that had been treated with the reference product Humira in the preceding study, FKB327-002 and were re-randomised to continue on Humira in Period I of FKB327-003 study. At week 30 all patients were transferred to treatment with FKB327. (Period II)

    Serious adverse events
    FKB327-FKB327 FKB327-Humira Humira-FKB327 Humira-Humira FKB327-FKB327-FKB327 FKB327-Humira-FKB327 Humira-FKB327-FKB327 Humira-Humira-FKB327
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 216 (2.31%)
    7 / 108 (6.48%)
    5 / 108 (4.63%)
    7 / 213 (3.29%)
    8 / 189 (4.23%)
    8 / 100 (8.00%)
    6 / 93 (6.45%)
    11 / 190 (5.79%)
         number of deaths (all causes)
    0
    0
    1
    1
    0
    0
    1
    1
         number of deaths resulting from adverse events
    0
    0
    1
    1
    0
    0
    1
    0
    Vascular disorders
    Lymphostasis
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    1 / 108 (0.93%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Hip arthroplasty
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    1 / 108 (0.93%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint surgery
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    1 / 213 (0.47%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Knee arthroplasty
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 108 (0.93%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Synovectomy
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    1 / 189 (0.53%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    1 / 189 (0.53%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervix carcinoma
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    1 / 108 (0.93%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Pregnancy
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    1 / 93 (1.08%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
    Additional description: no cause of death terminology recorded
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    1 / 93 (1.08%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 108 (0.93%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    1 / 108 (0.93%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Cervical dysplasia
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    1 / 189 (0.53%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 108 (0.93%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    1 / 189 (0.53%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    1 / 100 (1.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Maternal exposure during pregnancy
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    1 / 93 (1.08%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Muscle rupture
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    1 / 100 (1.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    1 / 108 (0.93%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    1 / 108 (0.93%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    1 / 100 (1.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    1 / 100 (1.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 108 (0.93%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    1 / 100 (1.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    1 / 189 (0.53%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    1 / 100 (1.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Anterior spinal artery syndrome
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    1 / 213 (0.47%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Oesophageal rupture
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    1 / 189 (0.53%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    1 / 213 (0.47%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis chronic
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    1 / 93 (1.08%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatocellular injury
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    1 / 100 (1.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Calculus urinary
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    1 / 93 (1.08%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    1 / 108 (0.93%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure chronic
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    1 / 213 (0.47%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 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
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    1 / 100 (1.00%)
    0 / 93 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 216 (0.46%)
    1 / 108 (0.93%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back disorder
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bursitis
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    1 / 100 (1.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    1 / 93 (1.08%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    1 / 189 (0.53%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    1 / 100 (1.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    1 / 108 (0.93%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Synovitis
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    1 / 213 (0.47%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    1 / 213 (0.47%)
    0 / 189 (0.00%)
    1 / 100 (1.00%)
    2 / 93 (2.15%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 1
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 108 (0.00%)
    1 / 108 (0.93%)
    1 / 213 (0.47%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    1 / 93 (1.08%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 108 (0.93%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    1 / 93 (1.08%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    1 / 93 (1.08%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 108 (0.93%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 216 (0.46%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningitis
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary mycosis
         subjects affected / exposed
    0 / 216 (0.00%)
    1 / 108 (0.93%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    0 / 189 (0.00%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 216 (0.00%)
    0 / 108 (0.00%)
    0 / 108 (0.00%)
    0 / 213 (0.00%)
    1 / 189 (0.53%)
    0 / 100 (0.00%)
    0 / 93 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    FKB327-FKB327 FKB327-Humira Humira-FKB327 Humira-Humira FKB327-FKB327-FKB327 FKB327-Humira-FKB327 Humira-FKB327-FKB327 Humira-Humira-FKB327
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    103 / 216 (47.69%)
    59 / 108 (54.63%)
    59 / 108 (54.63%)
    117 / 213 (54.93%)
    114 / 189 (60.32%)
    61 / 100 (61.00%)
    51 / 93 (54.84%)
    114 / 190 (60.00%)
    Musculoskeletal and connective tissue disorders
    Rheumatoid arthritis
         subjects affected / exposed
    12 / 216 (5.56%)
    7 / 108 (6.48%)
    5 / 108 (4.63%)
    8 / 213 (3.76%)
    7 / 189 (3.70%)
    6 / 100 (6.00%)
    4 / 93 (4.30%)
    8 / 190 (4.21%)
         occurrences all number
    15
    8
    7
    10
    9
    9
    4
    9
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    7 / 216 (3.24%)
    9 / 108 (8.33%)
    6 / 108 (5.56%)
    13 / 213 (6.10%)
    23 / 189 (12.17%)
    8 / 100 (8.00%)
    11 / 93 (11.83%)
    18 / 190 (9.47%)
         occurrences all number
    7
    9
    6
    16
    25
    8
    11
    20
    Bronchitis
         subjects affected / exposed
    10 / 216 (4.63%)
    3 / 108 (2.78%)
    2 / 108 (1.85%)
    11 / 213 (5.16%)
    5 / 189 (2.65%)
    3 / 100 (3.00%)
    5 / 93 (5.38%)
    8 / 190 (4.21%)
         occurrences all number
    10
    3
    2
    11
    6
    3
    5
    8
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 216 (1.39%)
    2 / 108 (1.85%)
    3 / 108 (2.78%)
    7 / 213 (3.29%)
    14 / 189 (7.41%)
    1 / 100 (1.00%)
    3 / 93 (3.23%)
    6 / 190 (3.16%)
         occurrences all number
    3
    2
    3
    7
    14
    2
    3
    6
    Urinary tract infection
         subjects affected / exposed
    6 / 216 (2.78%)
    3 / 108 (2.78%)
    3 / 108 (2.78%)
    4 / 213 (1.88%)
    9 / 189 (4.76%)
    3 / 100 (3.00%)
    5 / 93 (5.38%)
    7 / 190 (3.68%)
         occurrences all number
    7
    4
    5
    4
    11
    3
    8
    8
    Pharyngitis
         subjects affected / exposed
    6 / 216 (2.78%)
    3 / 108 (2.78%)
    3 / 108 (2.78%)
    4 / 213 (1.88%)
    5 / 189 (2.65%)
    2 / 100 (2.00%)
    6 / 93 (6.45%)
    4 / 190 (2.11%)
         occurrences all number
    11
    3
    3
    4
    5
    3
    6
    4

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Dec 2014
    Global Amendment 1 (substantial): changes were implemented following Regulatory Authority feed-back on the protocol for Study FKB327-002. These changes were made before the protocol was submitted in any country.
    23 Mar 2015
    Global Amendment 2 (substantial): following Regulatory Authority feed-back, changes were made to selected exclusion criteria that were part of the preceding study FKB327-002 protocol that should also be applied to the FKB327-003 protocol. In addition, the FKB327-002 completion status required for entry into FKB327-003 was clarified. Other administrative changes were completed to the protocol.
    18 Aug 2015
    Global Amendment 3 (substantial): changes were completed to the study protocol following realisation of a potential safety issue (latex allergy) which may have affected handling of the study drug for site staff and patients enrolled on the FKB327-003 study protocol. The issue concerned the comparator treatment arm only. In addition, a number of non substantial changes were introduced in this global amendment, i.e. an increase in the planned number of patients. Other minor administrative changes were completed.

    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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