Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Multicenter, Randomized, Parallel Group Study To Compare The Incidence Of Tocilizumab Related Infusion Reactions in Patients With Moderate To Severe Active RA, When Infusion is Given Over 31 Minutes Compared To 1 Hour

    Summary
    EudraCT number
    		 2011-002363-15
    Trial protocol
    		 IS   DK  
    Global end of trial date
    02 Sep 2013

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Jul 2016
    First version publication date
    06 Aug 2015
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ML27901
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01468077
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    Scientific contact
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.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
    25 Nov 2013
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    08 Jul 2013
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Sep 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The overall aim of this multicenter, randomized, parallel group study was to evaluate the incidence of tocilizumab related infusion reactions in participants with moderate to severe active Rheumatoid Arthritis (RA), when infusion was administered over 31 minutes (Fast Administration) compared to being administered over 1 hour (Normal Administration). The primary objective: - To compare incidence of tocilizumab infusion reactions between 60 minutes and 31 minutes dose administrations. The secondary objectives were: - To evaluate adverse events (AE) resulting from the two infusion times. - To evaluate the Disease Activity Score Based on 28-Joint Count (DAS28 ) less than (<)2.6 after 24 weeks of infusion. - To evaluate American College of Rheumatology Percent Improvement (ACR20, ACR50, ACR70 and ACR90) responses after 24 weeks of infusion.
    Protection of trial subjects
    The investigators were required to ensure this study was conducted in full conformance with the principles of the “Declaration of Helsinki” or with the laws and regulations of the country in which the research was conducted, whichever afforded the greater protection to the individual. The study conduct fully adhered to the principles outlined in “Guideline for Good Clinical Practice” International Conference on Harmonisation (ICH) Tripartite Guideline [January 1997] or with local law if it afforded greater protection to the participant. The investigators were also required to ensure compliance with the EU (European Union) Clinical Study Directive [2001/20/EC]. All investigators were trained according to Roche standard operational procedures (SOPs).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Sep 2011
    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
    Denmark: 41
    Country: Number of subjects enrolled
    Iceland: 6
    Worldwide total number of subjects
    47
    EEA total number of subjects
    47
    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)
    32
    From 65 to 84 years
    15
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Between 14 November 2011 to 02 September 2013, a total of 52 participants were screened and 47 were randomized into either the Fast or Normal Administration treatment groups. Five participants failed screening, due to Aspartate Aminotransferase (AST) levels above inclusion criteria (2), previous serious antibody reactions (2), and infection (1).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    There are no blinding details as this was an open-label study. Participants were randomized in groups of four with two participants for each arm, and all investigators picked numbered envelopes in sequential order.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Tocilizumab, Normal Administration
    Arm description
    		 Participants received tocilizumab 8 milligrams per kilogram (mg/kg) intravenously (IV) over 60 minutes once every 4 weeks for a total of 6 infusions during a 24-week treatment period.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    tocilizumab
    Investigational medicinal product code
    Other name
    RoActemra, Actemra
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received an infusion of 8 mg/kg tocilizumab every 4 weeks during the 24-week treatment period. The infusion was given a total of 6 times, at Week 0 (Day 1) and at Week 4, 8, 12, 16 and 20.

    Arm title
    		 Tocilizumab, Fast Administration
    Arm description
    		 Participants received tocilizumab 8 mg/kg IV once every 4 weeks for a total of 6 infusions during a 24-week treatment period. The first infusion (Baseline) was given over 60 minutes, and over 31 minutes the following 5 infusions.
    Arm type
    		 Experimental

    Investigational medicinal product name
    tocilizumab
    Investigational medicinal product code
    Other name
    RoActemra, Actemra
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received an infusion of 8 mg/kg tocilizumab every 4 weeks during the 24-week treatment period. The infusion was given a total of 6 times, at Week 0 (Day 1) and at Week 4, 8, 12, 16 and 20.

    Number of subjects in period 1
    		Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Started
    22
    25
    Completed
    18
    22
    Not completed
    4
    3
         Adverse Event
    2
    2
         Physician Decision
    1
    -
         Lack of efficacy
    1
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Tocilizumab, Normal Administration
    Reporting group description
    		 Participants received tocilizumab 8 milligrams per kilogram (mg/kg) intravenously (IV) over 60 minutes once every 4 weeks for a total of 6 infusions during a 24-week treatment period.

    Reporting group title
    Tocilizumab, Fast Administration
    Reporting group description
    		 Participants received tocilizumab 8 mg/kg IV once every 4 weeks for a total of 6 infusions during a 24-week treatment period. The first infusion (Baseline) was given over 60 minutes, and over 31 minutes the following 5 infusions.

    Reporting group values
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration Total
    Number of subjects
    		 22 25 47
    Age categorical
    Units: Subjects
    Age continuous
    Age of the ITT population at Baseline
    Units: years
        arithmetic mean (standard deviation)
    		 57.5 ± 11.8 59.8 ± 13.1 -
    Gender categorical
    Baseline gender characteristics of ITT population
    Units: Subjects
        Female
    		 17 20 37
        Male
    		 5 5 10

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Tocilizumab, Normal Administration
    Reporting group description
    		 Participants received tocilizumab 8 milligrams per kilogram (mg/kg) intravenously (IV) over 60 minutes once every 4 weeks for a total of 6 infusions during a 24-week treatment period.

    Reporting group title
    Tocilizumab, Fast Administration
    Reporting group description
    		 Participants received tocilizumab 8 mg/kg IV once every 4 weeks for a total of 6 infusions during a 24-week treatment period. The first infusion (Baseline) was given over 60 minutes, and over 31 minutes the following 5 infusions.

    Primary: Percentage of Participants With Any Infusion Reaction

    		 Close Top of page
    End point title
    		 Percentage of Participants With Any Infusion Reaction
    End point description
    An infusion reaction was defined as any AE that occurred during the infusion or during the 24 hours following the infusion and possibly or probably related to tocilizumab.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1), and Weeks 4, 8, 12, 16, and 20
    End point values
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Number of subjects analysed
    22 [1]
    25 [2]
    Units: Percentage of Participants
        number (not applicable)
    13.6
    12
    Notes
    [1] - Safety Analysis Set (SAS) Population: Randomized participants infused at least once with tocilizumab
    [2] - SAS Population
    Statistical analysis title
    		 Participants With Any Infusion Reactions
    Statistical analysis description
    The Confidence Interval calculated by Exact method based on binomial distribution
    Comparison groups
    Tocilizumab, Normal Administration v Tocilizumab, Fast Administration
    Number of subjects included in analysis
    47
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.0164
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2685
         upper limit
    		 0.2988

    Secondary: Percentage of Participants Discontinuing Tocilizumab in Response to an AE or a Serious Adverse Event (SAE)

    		 Close Top of page
    End point title
    		 Percentage of Participants Discontinuing Tocilizumab in Response to an AE or a Serious Adverse Event (SAE)
    End point description
    All occurrences of participants who received at least 1 infusion of tocilizumab and then stopped tocilizumab infusions due to an AE or SAE were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, and 24
    End point values
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Number of subjects analysed
    22 [3]
    25 [4]
    Units: Percentage of Participants
        number (not applicable)
    9
    8
    Notes
    [3] - SAS Population
    [4] - SAS Population
    No statistical analyses for this end point

    Secondary: Percentage of Participants Discontinuing Tocilizumab for Other Reasons

    		 Close Top of page
    End point title
    		 Percentage of Participants Discontinuing Tocilizumab for Other Reasons
    End point description
    Participants that stopped the administration of tocilizumab and discontinued the study prematurely due to reasons other than an AE or SAE were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks, 4, 8, 12, 16, 20, and 24
    End point values
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Number of subjects analysed
    22 [5]
    25 [6]
    Units: Percentage of Participants
        number (not applicable)
    9
    4
    Notes
    [5] - SAS Population
    [6] - SAS Population
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Increased Liver Enzyme Values of Greater Than (>)1.5 Times, or >3 Times, or >5 Times Over the Upper Limit of Normal (ULN) by Visit Among Participants Who Completed All Visits

    		 Close Top of page
    End point title
    		 Percentage of Participants With Increased Liver Enzyme Values of Greater Than (>)1.5 Times, or >3 Times, or >5 Times Over the Upper Limit of Normal (ULN) by Visit Among Participants Who Completed All Visits
    End point description
    Increased liver enzyme values defined as Alanine Aminotransferase (ALT) and AST values of >1.5 times, or >3 times, or >5 times over the ULN. Almost none of the participants had increased measurements of AST, thus only values of ALT were presented. None of the participants presented with increased values of ALT above 3 or 5 ULN at any of the visits. ITT Completers is defined as a subset of the participants in the ITT population who completed all study visits.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 4, 8, 12, 16, 20, and 24
    End point values
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Number of subjects analysed
    17 [7]
    21 [8]
    Units: Percentage of Participants
    number (not applicable)
        ALT>1.5 ULN Week 4
    12
    5
        ALT>1.5 ULN Week 8
    6
    10
        ALT>1.5 ULN Week 12
    6
    5
        ALT>1.5 ULN Week 16
    6
    10
        ALT>1.5 ULN Week 20
    12
    5
        ALT>1.5 ULN Week 24
    24
    5
    Notes
    [7] - ITT Completers with liver enzyme datasets for each analyzed visit
    [8] - ITT Completers with liver enzyme datasets for each analyzed visit
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Increased Lipid Values by Visit Among Participants Who Completed All Visits

    		 Close Top of page
    End point title
    		 Percentage of Participants With Increased Lipid Values by Visit Among Participants Who Completed All Visits
    End point description
    Increased levels of high density lipoproteins (HDL) equal to or greater than (≥)1.5 millimoles per liter (mmol/L), and low density lipoproteins (LDL) ≥4.1 mmol/L, and total cholesterol ≥5.1 mmol/L, are defined according to the Adult Treatment Panel III (ATP-III) guidelines.
    End point type
    Secondary
    End point timeframe
    Screening and Weeks 4, 8, 12, 16, 20, and 24
    End point values
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Number of subjects analysed
    18 [9]
    22 [10]
    Units: Percentage of Participants
    number (not applicable)
        High HDL (≥1.5 mmol/L), Screening
    44
    46
        High HDL (≥1.5 mmol/L), Week 4
    44
    55
        High HDL (≥1.5 mmol/L), Week 8
    50
    36
        High HDL (≥1.5 mmol/L), Week 12
    39
    50
        High HDL (≥1.5 mmol/L), Week 16
    44
    41
        High HDL (≥1.5 mmol/L), Week 20
    39
    36
        High HDL (≥1.5 mmol/L), Week 24
    44
    46
        High LDL (≥4.1 mmol/L), Screening
    0
    14
        High LDL (≥4.1 mmol/L), Week 4
    11
    27
        High LDL (≥4.1 mmol/L), Week 8
    6
    32
        High LDL (≥4.1 mmol/L), Week 12
    6
    36
        High LDL (≥4.1 mmol/L), Week 16
    6
    23
        High LDL (≥4.1 mmol/L), Week 20
    11
    32
        High LDL (≥4.1 mmol/L), Week 24
    6
    18
        High total cholesterol (≥5.1 mmol/L), Screening
    33
    59
        High total cholesterol (≥5.1 mmol/L), Week 4
    56
    73
        High total cholesterol (≥5.1 mmol/L), Week 8
    61
    73
        High total cholesterol (≥5.1 mmol/L), Week 12
    56
    68
        High total cholesterol (≥5.1 mmol/L), Week 16
    61
    64
        High total cholesterol (≥5.1 mmol/L), Week 20
    61
    59
        High total cholesterol (≥5.1 mmol/L), Week 24
    56
    64
    Notes
    [9] - ITT Completers
    [10] - ITT Completers
    No statistical analyses for this end point

    Secondary: Percentage of Participants With a Reduction of at Least 1.2 Points in DAS28 by Visit Among Participants Who Completed All Visits

    		 Close Top of page
    End point title
    		 Percentage of Participants With a Reduction of at Least 1.2 Points in DAS28 by Visit Among Participants Who Completed All Visits
    End point description
    Improvement in RA disease activity was measured by the DAS28 score, which is an index combining measurements of swollen and tender joints, acute phase response High sensitivity C-Reactive Protein (hsCRP), and global assessment of disease activity by the participant. A clinically meaningful improvement was defined as a reduction of at least 1.2 units in DAS28 during the study period. A low disease activity was defined as DAS28 <3.2, and remission was defined as DAS28 <2.6.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8, 12, 16, 20, and 24
    End point values
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Number of subjects analysed
    18 [11]
    22 [12]
    Units: Percentage of Participants
    number (not applicable)
        Week 4
    67
    55
        Week 8
    89
    73
        Week 12
    89
    82
        Week 16
    94
    77
        Week 20
    94
    82
        Week 24
    89
    86
    Notes
    [11] - ITT Completers
    [12] - ITT Completers
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving a DAS28 Score Below 3.2 (Low Disease Activity) by Visit Among Participants Who Completed all Visits

    		 Close Top of page
    End point title
    		 Percentage of Participants Achieving a DAS28 Score Below 3.2 (Low Disease Activity) by Visit Among Participants Who Completed all Visits
    End point description
    Improvement in RA disease activity was measured by the DAS28 score, which is an index combining measurements of swollen and tender joints, acute phase response hsCRP, and global assessment of disease activity by the participant. A clinically meaningful improvement was defined as a reduction of at least 1.2 units in DAS28 during the study period. A low disease activity was defined as DAS28 <3.2, and remission was defined as DAS28 <2.6.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8, 12, 16, 20, and 24
    End point values
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Number of subjects analysed
    18 [13]
    22 [14]
    Units: Percentage of Participants
    number (not applicable)
        Week 4
    44
    27
        Week 8
    67
    55
        Week 12
    78
    82
        Week 16
    94
    68
        Week 20
    89
    73
        Week 24
    83
    77
    Notes
    [13] - ITT Completers
    [14] - ITT Completers
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving a DAS28 Score Below 2.6 (Remission) by Visit Among Participants Who Completed All Visits

    		 Close Top of page
    End point title
    		 Percentage of Participants Achieving a DAS28 Score Below 2.6 (Remission) by Visit Among Participants Who Completed All Visits
    End point description
    Improvement in RA disease activity was measured by the DAS28 score, which is an index combining measurements of swollen and tender joints, acute phase response hsCRP, and global assessment of disease activity by the participant. A clinically meaningful improvement was defined as a reduction of at least 1.2 units in DAS28 during the study period. A low disease activity was defined as DAS28 <3.2, and remission was defined as DAS28 <2.6.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8, 12, 16, 20, and 24
    End point values
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Number of subjects analysed
    18 [15]
    22 [16]
    Units: Percentage of Participants
    number (not applicable)
        Week 4
    22
    9
        Week 8
    28
    36
        Week 12
    50
    73
        Week 16
    78
    46
        Week 20
    72
    59
        Week 24
    61
    55
    Notes
    [15] - ITT Completers
    [16] - ITT Completers
    No statistical analyses for this end point

    Secondary: DAS28 Score by Visit Among Participants Who Completed All Visits

    		 Close Top of page
    End point title
    		 DAS28 Score by Visit Among Participants Who Completed All Visits
    End point description
    Improvement in RA disease activity was measured by the DAS28 score, which is an index combining measurements of swollen and tender joints, acute phase response hsCRP, and global assessment of disease activity by the participant. A clinically meaningful improvement was defined as a reduction of at least 1.2 units in DAS28 during the study period. A low disease activity was defined as DAS28 <3.2, and remission was defined as DAS28 <2.6.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks, 4, 8, 12, 16, 20, and 24
    End point values
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Number of subjects analysed
    18 [17]
    22 [18]
    Units: Scores On A Scale
    arithmetic mean (standard deviation)
        Baseline (n=18, 21)
    5 ± 1.1
    5 ± 0.9
        Week 4 (n=18, 21)
    3.3 ± 0.8
    3.6 ± 1
        Week 8 (n=18, 22)
    2.9 ± 0.8
    3.1 ± 1.2
        Week 12 (n=18, 22)
    2.6 ± 0.9
    2.4 ± 1
        Week 16 (n=18, 21)
    2.3 ± 0.4
    2.6 ± 1
        Week 20 (n=18, 22)
    2.3 ± 0.6
    2.6 ± 0.9
        Week 24 (n=18, 22)
    2.3 ± 0.6
    2.5 ± 1
    Notes
    [17] - ITT Completers; n=the number of participants analyzed for the given parameter at the specific visit
    [18] - ITT Completers; n=the number of participants analyzed for the given parameter at the specific visit
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving American College of Rheumatology 20 Percent (%) Improvement (ACR20 Response) by Visit Among Participants Who Completed all Visits

    		 Close Top of page
    End point title
    		 Percentage of Participants Achieving American College of Rheumatology 20 Percent (%) Improvement (ACR20 Response) by Visit Among Participants Who Completed all Visits
    End point description
    ACR20 response is defined as an improvement of ≥20% in swollen joint count (SJC; 66 joints) and tender joint count (TJC; 68 joints) as well as ≥20% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; Health Assessment Questionnaire-Disability Index (HAQ-DI); and acute phase reactive factors (Erythrocyte Sedimentation Rate [ESR] or C-Reactive Protein [CRP]).
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8, 12, 16, 20, and 24
    End point values
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Number of subjects analysed
    18 [19]
    22 [20]
    Units: Percentage of Participants
    number (not applicable)
        Week 4
    50
    41
        Week 8
    67
    59
        Week 12
    72
    68
        Week 16
    83
    77
        Week 20
    83
    73
        Week 24
    89
    91
    Notes
    [19] - ITT Completers
    [20] - ITT Completers
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving ACR 50% Improvement (ACR50 Response) by Visit Among Participants Who Completed all Visits

    		 Close Top of page
    End point title
    		 Percentage of Participants Achieving ACR 50% Improvement (ACR50 Response) by Visit Among Participants Who Completed all Visits
    End point description
    ACR50 response is defined as an improvement of ≥50% in SJC (66 joints) and TJC (68 joints) as well as ≥50% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP).
    End point type
    Secondary
    End point timeframe
    Weeks, 4, 8, 12, 16, 20, and 24
    End point values
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Number of subjects analysed
    18 [21]
    22 [22]
    Units: Percentage of Participants
    number (not applicable)
        Week 4
    28
    18
        Week 8
    28
    36
        Week 12
    50
    50
        Week 16
    44
    46
        Week 20
    67
    55
        Week 24
    72
    73
    Notes
    [21] - ITT Completers
    [22] - ITT Completers
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving ACR 70% Improvement (ACR70 Response) by Visit Among Participants Who Completed All Visits

    		 Close Top of page
    End point title
    		 Percentage of Participants Achieving ACR 70% Improvement (ACR70 Response) by Visit Among Participants Who Completed All Visits
    End point description
    ACR70 response is defined as an improvement of ≥70% in SJC (66 joints) and TJC (68 joints) as well as ≥70% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP).
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8, 12, 16, 20 and 24
    End point values
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Number of subjects analysed
    18 [23]
    22 [24]
    Units: Percentage of Participants
    number (not applicable)
        Week 4
    11
    5
        Week 8
    17
    23
        Week 12
    22
    36
        Week 16
    11
    27
        Week 20
    22
    18
        Week 24
    22
    36
    Notes
    [23] - ITT Completers
    [24] - ITT Completers
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving ACR 90% Improvement (ACR90 Response) by Visit Among Participants Who Completed all Visits

    		 Close Top of page
    End point title
    		 Percentage of Participants Achieving ACR 90% Improvement (ACR90 Response) by Visit Among Participants Who Completed all Visits
    End point description
    ACR90 response is defined as an improvement of ≥90% in SJC (66 joints) and TJC (68 joints) as well as ≥90% improvement in at least 3 of the following 5 remaining ACR assessments: Patient Global Assessment of Pain; Patient Global Assessment of Disease Activity; Physician Global Assessment of Disease Activity; HAQ-DI; and acute phase reactive factors (ESR or CRP).
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8, 12, 16, 20 and 24
    End point values
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Number of subjects analysed
    18 [25]
    22 [26]
    Units: Percentage of Participants
    number (not applicable)
        Week 4
    0
    0
        Week 8
    0
    9
        Week 12
    0
    14
        Week 16
    0
    0
        Week 20
    6
    5
        Week 24
    6
    9
    Notes
    [25] - ITT Completers
    [26] - ITT Completers
    No statistical analyses for this end point

    Secondary: High Sensitivity C-Reactive Protein (hsCRP) Levels by Visit Among Participants Who Completed all Visits

    		 Close Top of page
    End point title
    		 High Sensitivity C-Reactive Protein (hsCRP) Levels by Visit Among Participants Who Completed all Visits
    End point description
    hsCRP is a marker for inflammation and is measured in milligrams per liter (mg/L). High levels of this protein indicate inflammation in diseases such as RA.
    End point type
    Secondary
    End point timeframe
    Screening, Baseline, Weeks 4, 8, 12, 16, 20, and 24
    End point values
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Number of subjects analysed
    18 [27]
    22 [28]
    Units: mg/L
    arithmetic mean (standard deviation)
        Screening
    22.8 ± 19.8
    25.9 ± 36
        Baseline
    23.5 ± 22.7
    27 ± 32.1
        Week 4
    4.7 ± 6.6
    3.1 ± 3.4
        Week 8
    3.3 ± 3.3
    4.5 ± 3.8
        Week 12
    3.2 ± 3.4
    2.6 ± 3.3
        Week 16
    2.8 ± 3.1
    3.1 ± 3.3
        Week 20
    2.9 ± 3
    3 ± 3.2
        Week 24
    3.2 ± 3.5
    3.4 ± 3.6
    Notes
    [27] - ITT Population
    [28] - ITT Population
    No statistical analyses for this end point

    Secondary: Modified Health Assessment Questionnaire (M-HAQ) Score by Visit Among Participants Who Completed all Visits

    		 Close Top of page
    End point title
    		 Modified Health Assessment Questionnaire (M-HAQ) Score by Visit Among Participants Who Completed all Visits
    End point description
    M-HAQ is a self-reported, valid assessment of functional disability in RA. Assessment based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. Scores range 0 to 3; without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 4, 8, 12, 20, and 24
    End point values
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Number of subjects analysed
    18 [29]
    22 [30]
    Units: Scores On A Scale
    arithmetic mean (standard deviation)
        Baseline
    1.29 ± 0.71
    1.5 ± 0.74
        Week 4
    0.97 ± 0.64
    1.1 ± 0.64
        Week 8
    0.79 ± 0.67
    0.95 ± 0.68
        Week 12
    0.8 ± 0.7
    0.98 ± 0.62
        Week 16
    0.82 ± 0.69
    0.94 ± 0.69
        Week 20
    0.75 ± 0.61
    1.05 ± 0.77
        Week 24
    0.68 ± 0.63
    1.07 ± 0.82
    Notes
    [29] - ITT Population
    [30] - ITT Population
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Improvement of at Least 0.22 Units in M-HAQ Compared to Baseline Per Visit Among Participants Who Completed all Visits

    		 Close Top of page
    End point title
    		 Percentage of Participants With Improvement of at Least 0.22 Units in M-HAQ Compared to Baseline Per Visit Among Participants Who Completed all Visits
    End point description
    M-HAQ is a self-reported, valid assessment of functional disability in RA. Assessment based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. Scores range 0 to 3; without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3.
    End point type
    Secondary
    End point timeframe
    Weeks 4, 8. 12, 20, and 24
    End point values
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Number of subjects analysed
    18 [31]
    22 [32]
    Units: Percentage of Participants
    number (not applicable)
        Week 4
    44.4
    45.5
        Week 8
    72.2
    59.1
        Week 12
    72.2
    54.5
        Week 16
    77.8
    63.6
        Week 20
    66.7
    59.1
        Week 24
    72.2
    50
    Notes
    [31] - ITT Completers
    [32] - ITT Completers
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Screening through Week 24 or early withdrawal. For early withdrawal two follow-up visits occurred; at 4 weeks and at 12 weeks after the last infusion. A telephone call was sufficient for the last visit if laboratory procedures were not needed.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    10.1
    Reporting groups
    Reporting group title
    Tocilizumab, Normal Administration
    Reporting group description
    		 Participants received tocilizumab 8 milligrams per kilogram (mg/kg) intravenously (IV) over 60 minutes once every 4 weeks for a total of 6 infusions during a 24-week treatment period.

    Reporting group title
    Tocilizumab, Fast Administration
    Reporting group description
    		 Participants received tocilizumab 8 mg/kg IV once every 4 weeks for a total of 6 infusions during a 24-week treatment period. The first infusion (Baseline) was given over 60 minutes, and over 31 minutes the following 5 times.

    Serious adverse events
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 25 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lymphoma cutis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Infective tenosynovitis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    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
    		 Tocilizumab, Normal Administration Tocilizumab, Fast Administration
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    20 / 22 (90.91%)
    17 / 25 (68.00%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Hypertension
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    2 / 22 (9.09%)
    3 / 25 (12.00%)
         occurrences all number
    2
    3
    Pain
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    2
    Chest pain
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Feeling cold
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    Menorrhagia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    2
    Dysphonia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 25 (4.00%)
         occurrences all number
    1
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 22 (4.55%)
    3 / 25 (12.00%)
         occurrences all number
    1
    3
    Migraine
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    1 / 22 (4.55%)
    4 / 25 (16.00%)
         occurrences all number
    2
    5
    Anaemia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Lymphadenopathy
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Thrombocytopenia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Dry eye
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Eye allergy
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    0 / 22 (0.00%)
    3 / 25 (12.00%)
         occurrences all number
    0
    3
    Diarrhoea
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 25 (8.00%)
         occurrences all number
    1
    2
    Nausea
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    2
    Dry mouth
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Haemorrhoids
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 25 (4.00%)
         occurrences all number
    1
    1
    Rash
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 25 (4.00%)
         occurrences all number
    1
    1
    Contusion
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Dermatitis acneiform
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Erythema
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 25 (4.00%)
         occurrences all number
    2
    2
    Rheumatoid arthritis
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 25 (4.00%)
         occurrences all number
    1
    3
    Joint swelling
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Myalgia
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    3 / 22 (13.64%)
    5 / 25 (20.00%)
         occurrences all number
    4
    6
    Rhinitis
         subjects affected / exposed
    3 / 22 (13.64%)
    0 / 25 (0.00%)
         occurrences all number
    3
    0
    Skin infection
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 25 (4.00%)
         occurrences all number
    1
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 22 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    2
    Wound infection
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 25 (4.00%)
         occurrences all number
    1
    1
    Abscess
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Abscess limb
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Herpes zoster
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Infective tenosynovitis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Oral herpes
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    Otitis media
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Pharyngitis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Vaginal infection
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Vulvovaginal candidiasis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Hypercholesterolaemia
         subjects affected / exposed
    2 / 22 (9.09%)
    3 / 25 (12.00%)
         occurrences all number
    2
    3

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat Apr 20 11:49:06 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA