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    Clinical Trial Results:
    A Multicenter, Randomized, Open-Label, Parallel-Group Usability Study of the Sarilumab Auto-Injector Device and a Prefilled Syringe in Patients with Moderate to Severe Active Rheumatoid Arthritis who are Candidates for Anti-IL6R Therapy

    Summary
    EudraCT number
    2012-004339-21
    Trial protocol
    PL  
    Global end of trial date
    11 Mar 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    22 Mar 2017
    First version publication date
    22 Mar 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MSC12665
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02057250
    WHO universal trial number (UTN)
    U1111-1130-9931
    Sponsors
    Sponsor organisation name
    Sanofi aventis recherche & développement
    Sponsor organisation address
    1 avenue Pierre Brossolette, Chilly-Mazarin, France, 91380
    Public contact
    Sanofi aventis recherche & développement, Trial Transparency Team, contact-US@sanofi.com
    Scientific contact
    Sanofi aventis recherche & développement, Trial Transparency Team, contact-US@sanofi.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
    12 Apr 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Mar 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To collect real-use data of the sarilumab auto-injector device (AID) used by rheumatoid arthritis (RA) subjects.
    Protection of trial subjects
    Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
    Background therapy
    Subjects received one or a combination of non-biologic disease modifying anti-rheumatic drug (DMARD) (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide, except for simultaneous combination use of leflunomide and methotrexate) as background therapy throughout the study.
    Evidence for comparator
    -
    Actual start date of recruitment
    18 Mar 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Chile: 30
    Country: Number of subjects enrolled
    Mexico: 18
    Country: Number of subjects enrolled
    Poland: 30
    Country: Number of subjects enrolled
    Russian Federation: 19
    Country: Number of subjects enrolled
    South Africa: 23
    Country: Number of subjects enrolled
    United States: 97
    Worldwide total number of subjects
    217
    EEA total number of subjects
    30
    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)
    166
    From 65 to 84 years
    50
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    The study was conducted at 53 centers in 6 countries. A total of 419 subjects were screened between 18 March 2014 and 14 October 2014, out of which 217 subjects were enrolled and treated.

    Pre-assignment
    Screening details
    Subjects were randomized in 1:1:1:1 ratio to Sarilumab 150 mg administered by AID or prefilled syringe (PFS) or Sarilumab 200 mg administered by AID or PFS. Subjects who completed 12-week AID assessment phase, were treated in open-label extension phase for 52 weeks.

    Period 1
    Period 1 title
    AID Assessment Phase
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Sarilumab 150 mg by AID (AID Assessment Phase)
    Arm description
    Sarilumab 150 mg every 2 weeks (q2w) administered by AID with one or a combination of non-biologic DMARD for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Sarilumab
    Investigational medicinal product code
    SAR153191, REGN88
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Sarilumab self-administered as a subcutaneous (SC) injection by AID in the abdomen or thigh.

    Arm title
    Sarilumab 150 mg by PFS (AID Assessment Phase)
    Arm description
    Sarilumab 150 mg q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Sarilumab
    Investigational medicinal product code
    SAR153191, REGN88
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Sarilumab self-administered as SC injection by PFS in the abdomen or thigh.

    Arm title
    Sarilumab 200 mg by AID (AID Assessment Phase)
    Arm description
    Sarilumab 200 mg q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Sarilumab
    Investigational medicinal product code
    SAR153191, REGN88
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Sarilumab self-administered as a SC injection by AID in the abdomen or thigh.

    Arm title
    Sarilumab 200 mg by PFS (AID Assessment Phase)
    Arm description
    Sarilumab 200 mg q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Sarilumab
    Investigational medicinal product code
    SAR153191, REGN88
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Sarilumab self-administered as a SC injection by PFS in the abdomen or thigh.

    Number of subjects in period 1
    Sarilumab 150 mg by AID (AID Assessment Phase) Sarilumab 150 mg by PFS (AID Assessment Phase) Sarilumab 200 mg by AID (AID Assessment Phase) Sarilumab 200 mg by PFS (AID Assessment Phase)
    Started
    56
    53
    52
    56
    Completed
    52
    50
    45
    54
    Not completed
    4
    3
    7
    2
         Other than specified above
             1
             1
             1
             1
         Adverse Event
             3
             2
             6
             1
    Period 2
    Period 2 title
    Extension Phase
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Sarilumab 150 mg by PFS (Extension Phase)
    Arm description
    Subjects who completed 12 week AID assessment phase received Sarilumab 150 mg q2w administered by PFS with one or a combination of non-biologic DMARD for 52 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Sarilumab
    Investigational medicinal product code
    SAR153191, REGN88
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Sarilumab self-administered as a SC injection by PFS in the abdomen or thigh.

    Number of subjects in period 2 [1]
    Sarilumab 150 mg by PFS (Extension Phase)
    Started
    192
    Treated
    188
    Completed
    156
    Not completed
    36
         Lack of efficacy
             10
         Entered in this period but not treated
             4
         Other than specified above
             7
         Adverse Event
             15
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: 9 subjects who completed AID Assessment phase did not enter extension phase.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Sarilumab 150 mg by AID (AID Assessment Phase)
    Reporting group description
    Sarilumab 150 mg every 2 weeks (q2w) administered by AID with one or a combination of non-biologic DMARD for 12 weeks.

    Reporting group title
    Sarilumab 150 mg by PFS (AID Assessment Phase)
    Reporting group description
    Sarilumab 150 mg q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.

    Reporting group title
    Sarilumab 200 mg by AID (AID Assessment Phase)
    Reporting group description
    Sarilumab 200 mg q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.

    Reporting group title
    Sarilumab 200 mg by PFS (AID Assessment Phase)
    Reporting group description
    Sarilumab 200 mg q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.

    Reporting group values
    Sarilumab 150 mg by AID (AID Assessment Phase) Sarilumab 150 mg by PFS (AID Assessment Phase) Sarilumab 200 mg by AID (AID Assessment Phase) Sarilumab 200 mg by PFS (AID Assessment Phase) Total
    Number of subjects
    56 53 52 56 217
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    53.7 ± 13.8 54.2 ± 14.2 55.9 ± 12.3 50.3 ± 12.8 -
    Gender categorical
    Units: Subjects
        Female
    45 43 44 49 181
        Male
    11 10 8 7 36

    End points

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    End points reporting groups
    Reporting group title
    Sarilumab 150 mg by AID (AID Assessment Phase)
    Reporting group description
    Sarilumab 150 mg every 2 weeks (q2w) administered by AID with one or a combination of non-biologic DMARD for 12 weeks.

    Reporting group title
    Sarilumab 150 mg by PFS (AID Assessment Phase)
    Reporting group description
    Sarilumab 150 mg q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.

    Reporting group title
    Sarilumab 200 mg by AID (AID Assessment Phase)
    Reporting group description
    Sarilumab 200 mg q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.

    Reporting group title
    Sarilumab 200 mg by PFS (AID Assessment Phase)
    Reporting group description
    Sarilumab 200 mg q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.
    Reporting group title
    Sarilumab 150 mg by PFS (Extension Phase)
    Reporting group description
    Subjects who completed 12 week AID assessment phase received Sarilumab 150 mg q2w administered by PFS with one or a combination of non-biologic DMARD for 52 weeks.

    Primary: Number of Validated AID Associated Product Technical Failures (PTFs)

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    End point title
    Number of Validated AID Associated Product Technical Failures (PTFs) [1] [2]
    End point description
    A PTF was defined as any product technical complaint (PTC) related to the use of the AID that had a validated technical cause. Each subject was given a diary having questions related to subject's ability to remove the cap, to start the injection, to complete the injection and regarding confirmation of completing the injection. Subjects were asked to answer the questions each time they self-inject the sarilumab. If the response was "no" to any of the first 3 questions, this was considered as a PTC. The used AID, for which PTC was reported, was sent to sponsor, examined and evaluated for the occurrence of a PTF. Modified intent-to-treat (mITT) population included all randomized subjects who received at least 1 dose of investigational medicinal product (IMP) with AID and attended at least 1 post-baseline visit during AID assessment phase of the study.
    End point type
    Primary
    End point timeframe
    Baseline up to Week 12
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics were reported, inferential statistics were not planned for primary endpoint.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only arms which are applicable to the endpoint are reported.
    End point values
    Sarilumab 150 mg by AID (AID Assessment Phase) Sarilumab 200 mg by AID (AID Assessment Phase)
    Number of subjects analysed
    56 [3]
    52 [4]
    Units: PTFs
        number (not applicable)
    0
    0
    Notes
    [3] - Number of Injections Analyzed: 312
    [4] - Number of Injections Analyzed: 288
    No statistical analyses for this end point

    Secondary: Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab

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    End point title
    Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab
    End point description
    AUC(0-tau) is defined as area under the serum concentration versus time curve calculated using the trapezoidal method during a dose interval, where dose interval was 2 weeks. Serum concentrations of sarilumab were analyzed using validated enzyme linked immunosorbent assay (ELISA). Pharmacokinetic (PK) population included all randomized subjects who received at least 1 dose of IMP and have least 1 PK parameter calculated using non compartmental methods following the first (Day 1) or sixth administration (Day 71). Here, 'n' signifies number of subjects with available data at specified category for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Week 0-2: pre-dose on Day 1, anytime post-dose on Day 3, Day 5, Day 8, Day 12, Day 15; Week 10-12: pre-dose on Day 71, anytime post-dose on Day 73, Day 75, Day 78, Day 82, Day 85
    End point values
    Sarilumab 150 mg by AID (AID Assessment Phase) Sarilumab 150 mg by PFS (AID Assessment Phase) Sarilumab 200 mg by AID (AID Assessment Phase) Sarilumab 200 mg by PFS (AID Assessment Phase)
    Number of subjects analysed
    56
    53
    52
    56
    Units: mg*day/L
    arithmetic mean (standard deviation)
        Week 0-2 (n=39, 34, 34, 41)
    131 ± 54.5
    152 ± 76.7
    235 ± 117
    227 ± 94.9
        Week 10-12 (n=44, 40, 36, 38)
    205 ± 126
    220 ± 130
    455 ± 294
    405 ± 244
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All AEs were collected from signature of the informed consent form up to the final visit (74 Weeks) regardless of seriousness or relationship to study drug.
    Adverse event reporting additional description
    Reported AEs are treatment-emergent AEs developed/worsened during'on treatment period' (first dose of IMP in AID phase up to last dose of IMP in extension phase+6 weeks). Safety population(SP) of AID phase: subjects who received at least 1 dose of IMP & SP of extension phase: subjects who continued extension phase & received at least 1 dose of IMP.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Sarilumab 150 mg by AID (AID Assessment Phase)
    Reporting group description
    Sarilumab 150 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.

    Reporting group title
    Sarilumab 150 mg by PFS (AID Assessment Phase)
    Reporting group description
    Sarilumab 150 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.

    Reporting group title
    Sarilumab 200 mg by AID (AID Assessment Phase)
    Reporting group description
    Sarilumab 200 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.

    Reporting group title
    Sarilumab 200 mg by PFS (AID Assessment Phase)
    Reporting group description
    Sarilumab 200 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.

    Reporting group title
    Sarilumab 150 mg by PFS (Extension Phase)
    Reporting group description
    Subjects who completed 12 week AID assessment phase received Sarilumab 150 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 52 weeks.

    Serious adverse events
    Sarilumab 150 mg by AID (AID Assessment Phase) Sarilumab 150 mg by PFS (AID Assessment Phase) Sarilumab 200 mg by AID (AID Assessment Phase) Sarilumab 200 mg by PFS (AID Assessment Phase) Sarilumab 150 mg by PFS (Extension Phase)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 53 (0.00%)
    3 / 52 (5.77%)
    4 / 56 (7.14%)
    19 / 188 (10.11%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Vascular disorders
    Deep Vein Thrombosis
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    1 / 52 (1.92%)
    0 / 56 (0.00%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis Superficial
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Pancreatic Carcinoma Metastatic
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Squamous Cell Carcinoma Of Skin
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    1 / 56 (1.79%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Endometrial Hyperplasia
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Injury, poisoning and procedural complications
    Femoral Neck Fracture
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Traumatic Arthritis
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Cardiac disorders
    Coronary Artery Occlusion
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Wolff-Parkinson-White Syndrome
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Respiratory, thoracic and mediastinal disorders
    Chronic Obstructive Pulmonary Disease
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Rheumatoid Lung
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Nervous system disorders
    Transient Ischaemic Attack
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Vertebrobasilar Insufficiency
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Gastrointestinal disorders
    Small Intestinal Obstruction
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Vomiting
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Hepatobiliary disorders
    Bile Duct Stone
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    1 / 52 (1.92%)
    0 / 56 (0.00%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    1 / 56 (1.79%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Lumbar Spinal Stenosis
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Osteoarthritis
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    1 / 52 (1.92%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Rheumatoid Arthritis
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    1 / 52 (1.92%)
    0 / 56 (0.00%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bursitis Infective Staphylococcal
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    1 / 56 (1.79%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    1 / 56 (1.79%)
    0 / 188 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Urinary Tract Infection
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences causally related to treatment / all
    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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Sarilumab 150 mg by AID (AID Assessment Phase) Sarilumab 150 mg by PFS (AID Assessment Phase) Sarilumab 200 mg by AID (AID Assessment Phase) Sarilumab 200 mg by PFS (AID Assessment Phase) Sarilumab 150 mg by PFS (Extension Phase)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    29 / 56 (51.79%)
    21 / 53 (39.62%)
    24 / 52 (46.15%)
    23 / 56 (41.07%)
    83 / 188 (44.15%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 56 (3.57%)
    1 / 53 (1.89%)
    3 / 52 (5.77%)
    2 / 56 (3.57%)
    1 / 188 (0.53%)
         occurrences all number
    2
    2
    3
    2
    1
    Injury, poisoning and procedural complications
    Accidental Overdose
         subjects affected / exposed
    0 / 56 (0.00%)
    0 / 53 (0.00%)
    2 / 52 (3.85%)
    3 / 56 (5.36%)
    8 / 188 (4.26%)
         occurrences all number
    0
    0
    2
    3
    12
    Contusion
         subjects affected / exposed
    3 / 56 (5.36%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    3 / 188 (1.60%)
         occurrences all number
    4
    0
    0
    0
    7
    Investigations
    Alanine Aminotransferase Increased
         subjects affected / exposed
    1 / 56 (1.79%)
    1 / 53 (1.89%)
    5 / 52 (9.62%)
    1 / 56 (1.79%)
    9 / 188 (4.79%)
         occurrences all number
    1
    1
    5
    1
    9
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    3 / 56 (5.36%)
    2 / 53 (3.77%)
    0 / 52 (0.00%)
    0 / 56 (0.00%)
    1 / 188 (0.53%)
         occurrences all number
    5
    2
    0
    0
    1
    Neutropenia
         subjects affected / exposed
    10 / 56 (17.86%)
    9 / 53 (16.98%)
    6 / 52 (11.54%)
    4 / 56 (7.14%)
    12 / 188 (6.38%)
         occurrences all number
    15
    16
    8
    5
    21
    Thrombocytopenia
         subjects affected / exposed
    4 / 56 (7.14%)
    1 / 53 (1.89%)
    2 / 52 (3.85%)
    1 / 56 (1.79%)
    3 / 188 (1.60%)
         occurrences all number
    4
    1
    2
    1
    4
    General disorders and administration site conditions
    Injection Site Erythema
         subjects affected / exposed
    2 / 56 (3.57%)
    2 / 53 (3.77%)
    4 / 52 (7.69%)
    4 / 56 (7.14%)
    7 / 188 (3.72%)
         occurrences all number
    4
    3
    8
    14
    33
    Injection Site Pruritus
         subjects affected / exposed
    1 / 56 (1.79%)
    2 / 53 (3.77%)
    0 / 52 (0.00%)
    4 / 56 (7.14%)
    5 / 188 (2.66%)
         occurrences all number
    2
    3
    0
    5
    25
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    1 / 56 (1.79%)
    0 / 53 (0.00%)
    0 / 52 (0.00%)
    3 / 56 (5.36%)
    0 / 188 (0.00%)
         occurrences all number
    1
    0
    0
    5
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    4 / 56 (7.14%)
    1 / 53 (1.89%)
    1 / 52 (1.92%)
    1 / 56 (1.79%)
    8 / 188 (4.26%)
         occurrences all number
    4
    1
    1
    1
    9
    Nasopharyngitis
         subjects affected / exposed
    4 / 56 (7.14%)
    1 / 53 (1.89%)
    1 / 52 (1.92%)
    2 / 56 (3.57%)
    4 / 188 (2.13%)
         occurrences all number
    4
    1
    1
    2
    4
    Pharyngitis
         subjects affected / exposed
    5 / 56 (8.93%)
    0 / 53 (0.00%)
    1 / 52 (1.92%)
    1 / 56 (1.79%)
    2 / 188 (1.06%)
         occurrences all number
    5
    0
    1
    1
    2
    Sinusitis
         subjects affected / exposed
    1 / 56 (1.79%)
    3 / 53 (5.66%)
    0 / 52 (0.00%)
    1 / 56 (1.79%)
    12 / 188 (6.38%)
         occurrences all number
    1
    3
    0
    1
    13
    Upper Respiratory Tract Infection
         subjects affected / exposed
    3 / 56 (5.36%)
    2 / 53 (3.77%)
    1 / 52 (1.92%)
    3 / 56 (5.36%)
    25 / 188 (13.30%)
         occurrences all number
    3
    3
    1
    4
    31
    Urinary Tract Infection
         subjects affected / exposed
    2 / 56 (3.57%)
    2 / 53 (3.77%)
    2 / 52 (3.85%)
    2 / 56 (3.57%)
    10 / 188 (5.32%)
         occurrences all number
    2
    2
    2
    2
    11

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 Jan 2014
    Following amendments were made: - Secondary endpoints (“use-related errors” were removed, “Failed drug deliveries” were added), as well as subject diary questions related to the AID user assessment were modified. - Caregivers were allowed to administer the investigational product under exceptional circumstances. - Analgesics with no anti-inflammatory properties were added to the permitted concomitant medication. - The reference to the Committee for Medicinal Products for Human Use (CHMP) guideline for supine blood pressure measurement was removed. - The objectives and the endpoints of the study were reordered.

    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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