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    Clinical Trial Results:
    A Phase 2 Exploratory Study of Mavrilimumab versus Anti-tumor Necrosis Factor in Subjects with Rheumatoid Arthritis

    Summary
    EudraCT number
    2011-005649-10
    Trial protocol
    DE   ES   PT   GR   HU   CZ   SK   GB  
    Global end of trial date
    06 Feb 2015

    Results information
    Results version number
    v2(current)
    This version publication date
    13 Nov 2016
    First version publication date
    16 Mar 2016
    Other versions
    v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    CD-IA-CAM-3001-1107
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01715896
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    MedImmune, LLC
    Sponsor organisation address
    Milstein Building, Granta Park, Cambridge, United Kingdom, CB21 6GH
    Public contact
    Marius Albulescu, Associate Medical Director, MedImmune, LLC, +44 301-398-0000, albulescum@medimmune.com
    Scientific contact
    Marius Albulescu, Associate Medical Director, MedImmune, LLC, +44 301-398-0000, albulescum@medimmune.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
    06 Feb 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Feb 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to explore the efficacy of mavrilimumab compared with golimumab in the treatment of adult participants 18-80 years of age with moderate-to-severe active rheumatoid arthritis (RA) who had an inadequate response to one or more conventional disease-modifying anti-rheumatic drugs (DMARDs) and/or one or two anti-tumor necrosis factor (TNF) agents (excluding golimumab) for efficacy or safety reasons.
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Participating participant signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    Participants with inadequate response to one or more conventional DMARDs and/or participants previously treated with one or two anti-TNF agents other than golimumab given for at least 3 months at various doses where the last agent was discontinued within 2 years prior to Day 1 due to inadequate response, safety, or intolerance, with the exception of the occurrence of serious adverse events (SAEs). Recommended Dose Regimens of Previous Anti-TNF Treatment were Adalimumab (Dosage of atleast 40 milligram [mg] every other week subcutaneous route), Infliximab (Dosage of at least 3 milligram per kilogram [mg/kg] at Weeks 0, 2, and 6, followed by a maintenance dose every 8 weeks thereafter intravenous route), Etanercept (Dosage of at least 25 mg administered twice weekly or 50 mg once weekly subcutaneous route) and Certolizumab (Dosage of 400 mg at Weeks 0, 2, and 4, followed by a maintenance dose of 200 mg every 2 weeks subcutaneous route). 'The last dose of anti-TNF agent should have been given at least 8 weeks prior to Day 1.
    Evidence for comparator
    -
    Actual start date of recruitment
    19 Mar 2013
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    3 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 21
    Country: Number of subjects enrolled
    Colombia: 10
    Country: Number of subjects enrolled
    Czech Republic: 26
    Country: Number of subjects enrolled
    Greece: 5
    Country: Number of subjects enrolled
    Hungary: 5
    Country: Number of subjects enrolled
    Israel: 12
    Country: Number of subjects enrolled
    Mexico: 12
    Country: Number of subjects enrolled
    Portugal: 2
    Country: Number of subjects enrolled
    Russian Federation: 22
    Country: Number of subjects enrolled
    Serbia: 5
    Country: Number of subjects enrolled
    Slovakia: 1
    Country: Number of subjects enrolled
    Spain: 6
    Country: Number of subjects enrolled
    United Kingdom: 11
    Worldwide total number of subjects
    138
    EEA total number of subjects
    56
    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)
    118
    From 65 to 84 years
    20
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Overall, 215 participants were screened, of which 77 participants were considered as screen failures and 138 participants were randomized and completed in the study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Carer, Assessor, Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Golimumab 50 mg alternating with Placebo
    Arm description
    Participants received alternating doses of golimumab 50 mg (Weeks 0, 4, 8, 12, 16, 20, and 24) and placebo matched to mavrilimumab (Weeks 2, 6, 10, 14, 18, and 22) injections subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.
    Arm type
    Experimental

    Investigational medicinal product name
    Placebo matched to mavrilimumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo matched to mavrilimumab (Weeks 2, 6, 10, 14, 18, and 22) injections subcutaneously in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

    Investigational medicinal product name
    Golimumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received golimumab 50 mg (Weeks 0, 4, 8, 12, 16, 20, and 24) injections subcutaneously for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

    Arm title
    Mavrilimumab 100 mg
    Arm description
    Participants received mavrilimumab 100 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.
    Arm type
    Experimental

    Investigational medicinal product name
    Mavrilimumab
    Investigational medicinal product code
    CAM-3001
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received mavrilimumab 100 mg injection subcutaneously every 2 weeks for 24 weeks.

    Number of subjects in period 1
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Started
    68
    70
    Completed
    65
    59
    Not completed
    3
    11
         Unspecified
    2
    5
         Consent withdrawn by subject
    1
    4
         Lost to follow-up
    -
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Golimumab 50 mg alternating with Placebo
    Reporting group description
    Participants received alternating doses of golimumab 50 mg (Weeks 0, 4, 8, 12, 16, 20, and 24) and placebo matched to mavrilimumab (Weeks 2, 6, 10, 14, 18, and 22) injections subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

    Reporting group title
    Mavrilimumab 100 mg
    Reporting group description
    Participants received mavrilimumab 100 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

    Reporting group values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg Total
    Number of subjects
    68 70 138
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    59 59 118
        Elderly (From 65-84 years)
    9 11 20
    Age Continuous |
    Units: years
        arithmetic mean (standard deviation)
    49.9 ± 11.4 50.2 ± 13.3 -
    Gender, Male/Female
    Units: Participants
        Female
    57 56 113
        Male
    11 14 25

    End points

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    End points reporting groups
    Reporting group title
    Golimumab 50 mg alternating with Placebo
    Reporting group description
    Participants received alternating doses of golimumab 50 mg (Weeks 0, 4, 8, 12, 16, 20, and 24) and placebo matched to mavrilimumab (Weeks 2, 6, 10, 14, 18, and 22) injections subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

    Reporting group title
    Mavrilimumab 100 mg
    Reporting group description
    Participants received mavrilimumab 100 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

    Primary: Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20) Responses at Day 169

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    End point title
    Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20) Responses at Day 169
    End point description
    The ACR20 was defined as greater than or equal to (>=) 20 percent (%) improvement, in: swollen joint count (SJC) and tender joint count (TJC) and >=20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity (PGA); physician global assessment of disease activity (MDGA); self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-reactive protein (CRP). If CRP was missing and Erythrocyte sedimentation rate (ESR) was present then ESR was to be used. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. The percentage of participants were calculated by logistic regression model method.
    End point type
    Primary
    End point timeframe
    Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: percentage of participants
        number (not applicable)
    65.6
    62
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for Percentage of Participants who Achieved ACR20 Responses at Day 169. P-value and 90% unconditional exact confidence interval (CI) was calculated using the model of logit (response) = strata + treatment.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.666
    Method
    Logit response Model
    Parameter type
    Percent difference
    Point estimate
    -3.5
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -16.8
         upper limit
    9.8

    Primary: Percentage of Participants who Achieved American College of Rheumatology 50 (ACR50) Responses at Day 169

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    End point title
    Percentage of Participants who Achieved American College of Rheumatology 50 (ACR50) Responses at Day 169
    End point description
    The ACR50 was defined as >=50% improvement, in: SJC and TJC and >=50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. If CRP was missing and ESR was present then ESR was to be used. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. The percentage of participants were calculated by logistic regression model method.
    End point type
    Primary
    End point timeframe
    Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: percentage of participants
        number (not applicable)
    43.4
    34.8
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for percentage of Participants who Achieved ACR50 Responses at Day 169. P-value and 90% unconditional exact CI was calculated using the model of logit (response) = strata + treatment.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.293
    Method
    Logit response Model
    Parameter type
    Percent difference
    Point estimate
    -8.6
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -22
         upper limit
    4.8

    Primary: Percentage of Participants who Achieved American College of Rheumatology 70 (ACR70) Responses at Day 169

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    End point title
    Percentage of Participants who Achieved American College of Rheumatology 70 (ACR70) Responses at Day 169
    End point description
    The ACR70 was defined as >=70% improvement, in: SJC and TJC and >=70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. If CRP was missing and ESR was present then ESR was to be used. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. The percentage of participants were calculated by logistic regression model method.
    End point type
    Primary
    End point timeframe
    Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: percentage of participants
        number (not applicable)
    25.9
    16.1
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for percentage of Participants who Achieved ACR70 Responses at Day 169. P-value and 90% unconditional exact CI was calculated using the model of logit (response) = strata + treatment.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.156
    Method
    Logit Response Model
    Parameter type
    Percent difference
    Point estimate
    -9.8
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -21.1
         upper limit
    1.4

    Primary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 169

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    End point title
    Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 169
    End point description
    The DAS28 (CRP) was calculated from the number of SJC and TJC using the 28 joints count, The DAS28(CRP) considers 28 of the 68 TJC and 28 of the 66 SJC and participant's global health (GH) using PGA of disease activity using the visual analogue scale (VAS) of 0 (= best), 100 (= worst) plus levels of CRP (milligram/Liter [mg/L]). Total score range: 0-9.4, higher score= more disease activity. DAS28 (CRP) less than (<) 3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. Participants with score less than 2.6 were analysed. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. The percentage of participants were calculated by logistic regression model method.
    End point type
    Primary
    End point timeframe
    Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: percentage of participants
        number (not applicable)
    29
    17.4
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 169. P-value and 90% unconditional exact CI was calculated using the model of logit (response) = strata + treatment.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.108
    Method
    Logit Response Model
    Parameter type
    Percent difference
    Point estimate
    -11.6
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -23.2
         upper limit
    0

    Primary: Percentage of Participants who Achieved Health Assessment Questionnaire Disability Index (HAQ-DI) Score Improvement From Baseline and >= 0.25 at Day 169

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    End point title
    Percentage of Participants who Achieved Health Assessment Questionnaire Disability Index (HAQ-DI) Score Improvement From Baseline and >= 0.25 at Day 169
    End point description
    The HAQ-DI: 20-item scale assessing participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arising, eating, hygiene, walking, reaching, grip, and errands/chores over past week. Each item was scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range from 0 to 3; where 0 = least difficulty and 3 = extreme difficulty. Participants with change from baseline more than or equal to (>=) 0.25 were reported. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. The percentage of participants were calculated by logistic regression model method.
    End point type
    Primary
    End point timeframe
    Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: percentage of participants
        number (not applicable)
    69
    58.7
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for Percentage of Participants who Achieved Health Assessment Questionnaire Disability Index (HAQ-DI) Score >= 0.25 at Day 169. P-value and 90% unconditional exact CI was calculated using the model of logit (response) = strata + treatment.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.208
    Method
    Logit Response Model
    Parameter type
    Percent difference
    Point estimate
    -10.3
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -23.7
         upper limit
    3

    Secondary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

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    End point title
    Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
    End point description
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and Day 169 that were absent before treatment or that worsened relative to pretreatment state. TEAE and TESAE were reported as per relatedness and severity. The safety population included all participants who received any amount of study medication.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: participants
        TEAEs
    29
    36
        TESAEs
    3
    2
        Investigational-product-related TEAE
    12
    11
        Severe TEAE
    1
    3
        Acute TEAEs
    5
    7
        Acute Severe TEAE
    0
    1
        Investigational-product-related TESAE
    0
    2
    No statistical analyses for this end point

    Secondary: Number of Participants with Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)

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    End point title
    Number of Participants with Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)
    End point description
    Any medically significant change in laboratory evaluations were recorded as adverse events. Following parameters were analyzed for laboratory examination: hematology (leukocytosis, neutropenia, anaemia of chronic disease); serum chemistry (alanine aminotransferase, blood parathyroid hormone, gamma glutamyl transferase, hepatic enzyme, dyslipidaemia, hypercholesterolaemia, hyperglycaemia, hyperlipidaemia, hypertriglyceridaemia); urinalysis. The safety population included all participants who received any amount of study medication.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: participants
        Leukocytosis
    0
    2
        Neutropenia
    0
    0
        Anaemia of chronic disease
    0
    0
        Alanine aminotransferase increased
    2
    0
        Blood parathyroid hormone increased
    0
    1
        Gamma-glutamyltransferase increased
    1
    0
        Hepatic enzyme increased
    2
    3
        Dyslipidaemia
    2
    0
        Hypercholesterolaemia
    2
    0
        Hyperglycaemia
    0
    1
        Hyperlipidaemia
    0
    1
        Hypertriglyceridaemia
    0
    1
        Urinalysis
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)

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    End point title
    Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)
    End point description
    Vital sign assessments included blood pressure, pulse rate, temperature, weight and respiration rate. Vital signs abnormalities reported as TEAEs were reported. The safety population included all participants who received any amount of study medication.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: participants
        Hypertension
    0
    1
        Pyrexia
    2
    0
    No statistical analyses for this end point

    Secondary: Number of Participants With Pulmonary Function Test Values Below Threshold Values Based on Percent Change From Baseline at Day 85 and 169

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    End point title
    Number of Participants With Pulmonary Function Test Values Below Threshold Values Based on Percent Change From Baseline at Day 85 and 169
    End point description
    Pulmonary function testing were performed by spirometry to assess forced expiratory volume in 1 second (FEV1), in 6 second (FEV6), forced vital capacity (FVC), and diffusing capacity for carbon monoxide (DLCO). FEV1 was maximal volume of air exhaled in first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. DLCO is a pulmonary function test that measures the partial pressure difference between inspired and expired carbon monoxide. The percentage of predicted values of these pulmonary function tests were calculated based on decreases from baseline and categorized as more than (>) 20% reduction (RD) and absolute value (AV) less than (<) 80% predicted (PR). The safety population included all participants who received any amount of investigational product.
    End point type
    Secondary
    End point timeframe
    Day 85 and 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68 [1]
    70 [2]
    Units: participants
        Day 85: FEV1 >20% RD (n=64, 63)
    1
    0
        Day 169: FEV1 >20% RD (n=64, 64)
    4
    1
        Day 85: FEV1 >20% RD and AV <80% PR (n=64, 63)
    1
    0
        Day 169: FEV1 >20% RD and AV <80% PR (n=64, 64)
    4
    1
        Day 85: FEV6 >20% RD (n=54, 55)
    1
    1
        Day 169: FEV6 >20% RD (n=54, 56)
    4
    0
        Day 85: FEV6 >20% RD and AV <80% PR (n=54, 55)
    0
    1
        Day 169: FEV6 >20% RD and AV <80% PR (n=54, 56)
    2
    0
        Day 85: FVC >20% RD (n=64, 63)
    0
    0
        Day 169: FVC >20% RD (n=64, 64)
    2
    1
        Day 85: FVC >20% RD and AV <80% PR (n=64, 63)
    0
    0
        Day 169: FVC >20% RD and AV <80% PR (n=64, 64)
    2
    1
        Day 85: DLCO >15-20% RD (n=18, 21)
    1
    0
        Day 169: DLCO >15-20% RD (n=22, 23)
    0
    0
        Day 85: DLCO >20% RD (n=18, 21)
    1
    0
        Day 169: DLCO >20% RD (n=22, 23)
    1
    0
    Notes
    [1] - "n" signifies participants evaluable for the specified value parameter for each arm, respectively.
    [2] - "n" signifies participants evaluable for the specified value parameter for each arm, respectively.
    No statistical analyses for this end point

    Secondary: Dyspnea Score at Day 169

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    End point title
    Dyspnea Score at Day 169
    End point description
    Borg dyspnea scale was a validated participant reported outcome assessing participant’s perceived difficulty in breathing (dyspnea). The scale ranges from 0 (nothing at all) to 10 (maximal difficulty). Higher scores indicated greater difficulty in breathing. The safety population included all participants who received any amount of investigational product. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.
    End point type
    Secondary
    End point timeframe
    Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    64
    63
    Units: units on a scale
        arithmetic mean (standard deviation)
    0.34 ± 0.81
    0.42 ± 0.73
    No statistical analyses for this end point

    Secondary: Change From Baseline in Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Score at Day 169

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    End point title
    Change From Baseline in Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Score at Day 169
    End point description
    DAS28 (CRP) calculated swollen joint count (SJC) and tender joint count (TJC) using the 28 joints, general health (GH) using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and CRP (milligram per liter [mg/L]). Total score range: 0-9.4, higher score= more disease activity. DAS28 (CRP) less than (<) 3.2 = low disease activity, greater than or equal to (>=) 3.2 to 5.1 = moderate to high disease activity and <2.6= remission. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. Here "n" signifies participants who were evaluable for this measure for the specified threshold value mentioned parameter for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n=68, 70)
    5.72 ± 0.83
    5.82 ± 0.96
        Day 169 (n=62, 62)
    -2.4 ± 1.42
    -2.11 ± 1.3
    No statistical analyses for this end point

    Secondary: Change From Baseline in Continuous American College of Rheumatology (ACRn) Score at Day 169

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    End point title
    Change From Baseline in Continuous American College of Rheumatology (ACRn) Score at Day 169
    End point description
    ACR score - continuous (ACRn) was defined as the minimum of the percentage improvement in TJC, SJC and the median of the percentage improvements in the other five components of the ACR criteria (participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; disability index of the HAQ; and CRP). Total score range was -100 to 100, where negative numbers indicated worsening and positive numbers indicated improvement. Mean indicates adjusted mean (Adj mean). The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    60
    61
    Units: units on a scale
        arithmetic mean (standard error)
    40.49 ± 5.406
    33.06 ± 5.199
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for Change From Baseline in Continuous American College of Rheumatology (ACRn) Score at Day 169. An estimate of the treatment difference and its 90% CI was computed by means of repeated measures model, adjusted for baseline and including a treatment by visit interaction term.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    121
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.213
    Method
    Repeated measures model
    Parameter type
    Adjusted Mean difference
    Point estimate
    -7.42
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -17.24
         upper limit
    2.4

    Secondary: American College of Rheumatology (ACR) Hybrid Score at Day 169

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    End point title
    American College of Rheumatology (ACR) Hybrid Score at Day 169
    End point description
    ACR Hybrid score was defined as the minimum of the percentage improvement in TJC, SJC and the median of the percentage improvements in the other five components of the ACR criteria (participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; disability index of the HAQ; and CRP). Total score range was -100 to 100, where negative numbers indicated worsening and positive numbers indicated improvement. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group.
    End point type
    Secondary
    End point timeframe
    Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: units on a scale
        median (full range (min-max))
    49.99 (-9 to 98.2)
    41.66 (-1 to 90.3)
    No statistical analyses for this end point

    Secondary: Number of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 169

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    End point title
    Number of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 169
    End point description
    DAS28 (CRP) response by EULAR category were used to measure individual response as none, moderate, and good, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline >1.2 with baseline DAS28 (CRP) <3.2; moderate response: change from baseline >1.2 with baseline DAS28 (CRP) >=3.2 to less than or equal to (=<) 5.1 or change from baseline >=0.6 to =< 1.2 with baseline DAS28 (CRP) >=3.2 to =<5.1; no response: change from baseline <0.6 or change from baseline >=0.6 and =<1.2 with baseline DAS28 (CRP) >5.1. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group.
    End point type
    Secondary
    End point timeframe
    Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: participants
        No response
    12
    16
        Moderate response
    28
    35
        Good response
    28
    19
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for Number of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 169. Odds ratio, 90% CI and p-value were was calculated using proportional odds analysis of response model including treatment as a factor.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.129
    Method
    Proportional odds analysis
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.61
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.36
         upper limit
    1.04

    Secondary: Number of Participants With DAS28 (CRP) Remission and Low Disease Activity at Day 169

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    End point title
    Number of Participants With DAS28 (CRP) Remission and Low Disease Activity at Day 169
    End point description
    DAS28 (CRP) calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and CRP (mg/L). Total score range: 0-9.4, higher score= more disease activity. Remission was defined as less than 2.6 DAS28 (CRP) score. Low disease activity was defined as less than 3.2 DAS28 (CRP) score. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group.
    End point type
    Secondary
    End point timeframe
    Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: participants
        DAS28 (CRP) Remission
    20
    12
        Low Disease Activity
    28
    20
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for Number of Participants With DAS28 (CRP) Remission at Day 169. 90% CI was calculated for the treatment difference in proportion of responders using logisitic regression with strata and treatment as factors.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.108 [3]
    Method
    Regression, Logistic
    Parameter type
    Percent difference
    Point estimate
    -11.6
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -23.2
         upper limit
    0
    Notes
    [3] - P-value estimated from fisher's exact test when number of golimumab or active responders was less than 5.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Analysis reported for Number of Participants With Low Disease Activity at Day 169. 90% CI was calculated for the treatment difference in proportion of responders using logisitic regression with strata and treatment as factors.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.145
    Method
    Regression, Logistic
    Parameter type
    Percent difference
    Point estimate
    -11.7
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -24.8
         upper limit
    1.4

    Secondary: Time to Onset DAS28 (CRP) remission at Day 169

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    End point title
    Time to Onset DAS28 (CRP) remission at Day 169
    End point description
    The DAS28 (CRP) was calculated from the number of SJC and TJC using the 28 joints count, The DAS28 (CRP) considers 28 of the 68 TJC and 28 of the 66 SJC and participant's global health (GH) using PGA of disease activity using the VAS of 0 (= best), 100 (= worst) plus levels of CRP (mg/L). Total score range: 0-9.4, higher score= more disease activity. DAS28 (CRP) <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. Participants with score less than 2.6 were analysed. Onset of DAS28(CRP) remission <=2.6 defined as the first study day in which the DAS28 score met the criteria. The mITT population analysis set included all participants who were at risk in the treatment group corresponding to their randomized treatment group. Here, "N" is number of participants analysed for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    20
    12
    Units: days
        median (confidence interval 90%)
    57 (29 to 112)
    113 (57 to 141)
    Statistical analysis title
    Statistical analysis 1
    Comparison groups
    Golimumab 50 mg alternating with Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.328 [4]
    Method
    Logrank
    Confidence interval
    Notes
    [4] - P-value was calculated using the Log rank test

    Secondary: Duration of DAS28 (CRP) Remission at Day 169

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    End point title
    Duration of DAS28 (CRP) Remission at Day 169
    End point description
    The DAS28 (CRP) was calculated from the number of SJC and TJC using the 28 joints count, The DAS28(CRP) considers 28 of the 68 TJC and 28 of the 66 SJC and participant's global health (GH) using PGA of disease activity using the VAS of 0 (= best), 100 (= worst) plus levels of CRP (mg/L). Total score range: 0-9.4, higher score= more disease activity. DAS28 (CRP) <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. Participants with score less than 2.6 were analysed. Duration of DAS28(CRP) remission for each subject was defined as number of days from onset of remission to when the subject was no longer in remission. The mITT population analysis set included all participants who were at risk in the treatment group corresponding to their randomized treatment group. Here, "N" is number of participants analysed for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    20
    12
    Units: days
        arithmetic mean (standard error)
    105 ± 0.24
    69.6 ± 0.15
    Statistical analysis title
    Statistical analysis 1
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.003 [5]
    Method
    Weibull model
    Confidence interval
    Notes
    [5] - P-value was calculated using an Weibull model.

    Secondary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) < 2.6 at Day 169

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    End point title
    Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) < 2.6 at Day 169
    End point description
    The DAS28 (ESR) calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]). Total score range: 0-9.4, higher score = more disease activity. DAS28 (ESR) <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. The percentage of participants were calculated by logistic regression model method.
    End point type
    Secondary
    End point timeframe
    Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: percentage of participants
        number (not applicable)
    19
    17.3
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 169. 90% CI was calculated for the treatment difference in proportion of responders using logisitic regression with strata and treatment as factors.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.795 [6]
    Method
    Regression, Logistic
    Parameter type
    Percent difference
    Point estimate
    -1.7
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -12.4
         upper limit
    9
    Notes
    [6] - P-value estimated from fisher's exact test when number of golimumab or active responders was less than 5.

    Secondary: Percentage of Participants who Achieved Simplified Disease Activity Index (SDAI) remission at Day 169

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    End point title
    Percentage of Participants who Achieved Simplified Disease Activity Index (SDAI) remission at Day 169
    End point description
    The SDAI was the numerical sum of five outcome parameters: TJC and SJC based on a 28-joint assessment, patient global assessment and physician global assessment assessed on 0 - 10 centimetre (cm) VAS; and C-reactive protein (CRP) (milligram per deciliter [mg/dL]). The SDAI total score ranges from 0 to 86, where higher scores indicates greater affection due to disease activity. SDAI remission was defined as a score less than or equal to 3.3. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. The percentage of participants were calculated by logistic regression model method.
    End point type
    Secondary
    End point timeframe
    Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: percentage of participants
        number (not applicable)
    18.9
    7.2
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for Percentage of Participants who Achieved Simplified Disease Activity Index (SDAI) remission at Day 169. 90% CI was calculated for the treatment difference in proportion of responders using logisitic regression with strata and treatment as factors.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.048
    Method
    Regression, Logistic
    Parameter type
    Percent difference
    Point estimate
    -11.7
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -21
         upper limit
    -2.5

    Secondary: Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Day 169

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    End point title
    Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Day 169
    End point description
    The CDAI was the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, patient global assessment and physician global assessment assessed on 0 - 10 cm VAS. The CDAI total score ranges from 0 to 76 where higher scores indicates greater affection due to disease activity. CDAI remission was defined as a score less than or equal to 2.8. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group.
    End point type
    Secondary
    End point timeframe
    Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: percentage of participants
        number (not applicable)
    17.6
    5.7
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Day 169. 90% CI was calculated for the treatment difference in proportion of responders using logisitic regression with strata and treatment as factors.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.035
    Method
    Regression, Logistic
    Parameter type
    Percent difference
    Point estimate
    -11.9
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -20.6
         upper limit
    -3.1

    Secondary: Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission at Day 169

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    End point title
    Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission at Day 169
    End point description
    The ACR/EULAR remission was defined as swollen joint count (0-66), tender joint count (0-68), CRP (mg/dL) and participant global assessment (0-10) all less than or equal to one. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group.
    End point type
    Secondary
    End point timeframe
    Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: percentage of participants
        number (not applicable)
    8.9
    1.4
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for Percentage of Participants With American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Remission at Day 169. 90% CI was calculated for the treatment difference in proportion of responders using logisitic regression with strata and treatment as factors.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.061
    Method
    Regression, Logistic
    Parameter type
    Percent difference
    Point estimate
    -7.5
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -13.6
         upper limit
    -1.5

    Secondary: Mean Change From Baseline in Swollen and Tender Joint Count at Day 169

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    End point title
    Mean Change From Baseline in Swollen and Tender Joint Count at Day 169
    End point description
    Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form, no swelling = 0, swelling =1. Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form, no tenderness = 0, tenderness = 1. Mean here indicates adjusted mean. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: joint count
    arithmetic mean (standard error)
        SJC: Baseline (n=68, 70)
    14.49 ± 0.779
    14.07 ± 0.824
        SJC: Change at Day 169 (n=64, 64)
    -10.07 ± 0.777
    -10.08 ± 0.747
        TJC: Baseline (n=68, 70)
    24.93 ± 1.662
    25.04 ± 1.543
        TJC: Change at Day 169 (n=64, 64)
    -15.42 ± 1.457
    -14.19 ± 1.399
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for change from baseline in swollen joint count at Day 169. An estimate of the treatment difference and its 90% CI was computed by means of repeated measures model, adjusted for baseline and including terms for treatment group, visit and treatment by visit interaction.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.993
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.01
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -1.33
         upper limit
    1.32
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Analysis reported for change from baseline in Tender joint count at Day 169. An estimate of the treatment difference and its 90% CI was computed by means of repeated measures model, adjusted for baseline and including terms for treatment group, visit and treatment by visit interaction.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.424
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    1.23
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -1.31
         upper limit
    3.77

    Secondary: Mean Change From Baseline in Patient Assessment of Pain at Day 169

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    End point title
    Mean Change From Baseline in Patient Assessment of Pain at Day 169
    End point description
    Participants rated the severity of arthritis pain on a 0 to 100 millimeter (mm) Visual Analogue Scale (VAS), where 0 mm = no pain and 100 mm = most severe pain. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: millimeter (mm)
    arithmetic mean (standard error)
        Baseline (n=68, 70)
    66.93 ± 2.352
    69.81 ± 2.015
        Change at Day 169 (n=64, 64)
    -29.61 ± 3.843
    -24.72 ± 3.727
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for Mean Change From Baseline in Patient Assessment of Pain at Day 169. An estimate of the treatment difference and its 90% CI was computed by means of repeated measures model, adjusted for baseline and including terms for treatment group, visit and treatment by visit interaction.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.272
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    4.89
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -2.46
         upper limit
    12.24

    Secondary: Mean Change From Baseline in Patient Global Assessment (PGA) of Disease Activity at Day 169

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    End point title
    Mean Change From Baseline in Patient Global Assessment (PGA) of Disease Activity at Day 169
    End point description
    Participants responded to a question, "Considering all the ways your arthritis affects you, how are you feeling today?" by using a 0 - 100 mm VAS, where 0 = very well and 100 = very poorly. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: mm
    arithmetic mean (standard error)
        Baseline (n=68, 70)
    67.57 ± 2.219
    68.53 ± 2.212
        Change at Day 169 (n=64, 64)
    -28.5 ± 3.773
    -24.04 ± 3.671
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for Mean Change From Baseline in Patient Global Assessment (PGA) of Disease Activity at Day 169. An estimate of the treatment difference and its 90% CI was computed by means of repeated measures model, adjusted for baseline and including terms for treatment group, visit and treatment by visit interaction.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.319
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    4.46
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -2.92
         upper limit
    11.84

    Secondary: Mean Change From Baseline in Physician Global Assessment of Disease Activity (MDGA) at Day 169

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    End point title
    Mean Change From Baseline in Physician Global Assessment of Disease Activity (MDGA) at Day 169
    End point description
    Physician Global Assessment of Arthritis was measured by asking the physician to assess the participant's current arthritis disease activity by placing a vertical line on a 0 to 10 cm VAS, where 0 cm = very good and 10 cm = very bad. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: centimeter (cm)
    arithmetic mean (standard error)
        Baseline (n=68, 70)
    6.89 ± 0.159
    7.04 ± 0.169
        Change at Day 169 (n=64, 64)
    -4.28 ± 0.317
    -4.11 ± 0.307
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for Mean Change From Baseline in Physician Global Assessment of Disease Activity (MDGA) at Day 169. An estimate of the treatment difference and its 90% CI was computed by means of repeated measures model, adjusted for baseline and including terms for treatment group, visit and treatment by visit interaction.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.64
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    0.16
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -0.42
         upper limit
    0.74

    Secondary: Mean Change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Day 169

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    End point title
    Mean Change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Day 169
    End point description
    HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item was scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range from 0 to 3; where 0 = least difficulty and 3 = extreme difficulty. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively
    End point type
    Secondary
    End point timeframe
    Baseline and Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: units on a scale
    arithmetic mean (standard error)
        Baseline (n=68, 70)
    1.58 ± 0.063
    1.59 ± 0.07
        Change at Day 169 (n=64, 64)
    -0.59 ± 0.081
    -0.4 ± 0.078
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for Mean Change from Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Day 169. An estimate of the treatment difference and its 90% CI was computed by means of repeated measures model, adjusted for baseline and including terms for treatment group, visit and treatment by visit interaction.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    138
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.055
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    0.18
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.03
         upper limit
    0.34

    Secondary: Ratio of Change C-Reactive Protein (CRP) at Day 169 to Baseline

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    End point title
    Ratio of Change C-Reactive Protein (CRP) at Day 169 to Baseline
    End point description
    The ratio of change from baseline for CRP was analyzed and reported. The CRP is a substance produced by the liver that increases in the presence of inflammation in the body. The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement in underlying disease. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. Here "N" (Number of participants analyzed) signifies those participants who were evaluable for this measure.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    64
    64
    Units: ratio
        geometric mean (geometric coefficient of variation)
    0.5036 ± 344
    0.5142 ± 100.9
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for Ratio of Change C-Reactive Protein (CRP) at Day 169 to Baseline. An estimate of the treatment difference and its 90% CI was computed by means of repeated measures model including terms for baseline as a continuous covariate and treatment as a factor was used for the analysis.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    128
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.752
    Method
    Repeated measures model
    Parameter type
    Adjusted geometric mean ratio
    Point estimate
    1.06
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.79
         upper limit
    1.41

    Secondary: Erythrocyte Sedimentation Rate (ESR) at Day 169

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    End point title
    Erythrocyte Sedimentation Rate (ESR) at Day 169
    End point description
    ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube. The farther the red blood cells have descended, the greater the inflammatory response. The mITT population analysis set included all participants in the treatment group corresponding to their randomized treatment group. Here "N" (Number of participants analyzed) signifies those participants who were evaluable for this measure. "n'' signifies participants evaluable for specified category for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    64
    64
    Units: millimeter per hour (mm/h)
        geometric mean (standard deviation)
    26.8 ± 21
    27.8 ± 20.8
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Analysis reported for Ratio of Erythrocyte Sedimentation Rate (ESR) at Day 169 to Baseline. An estimate of the treatment difference and its 90% CI was computed by means of repeated measures model including terms for baseline as a continuous covariate and treatment as a factor was used for the analysis.
    Comparison groups
    Mavrilimumab 100 mg v Golimumab 50 mg alternating with Placebo
    Number of subjects included in analysis
    128
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.725
    Method
    Repeated measures model
    Parameter type
    Adjusted geometric mean ratio
    Point estimate
    1.05
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.84
         upper limit
    1.3

    Secondary: Serum Concentrations of Mavrilimumab

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    End point title
    Serum Concentrations of Mavrilimumab [7]
    End point description
    Serum concentrations after subcutaneous dose of mavrilimumab were calculated. The pharmacokinetic (PK) population included all participants who received mavrilimumab and for whom serum concentrations of mavrilimumab were available for PK data analyses. Here "n" signifies participants who were evaluable for the specified time point for each this arm respectively.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 8, 15, 29, 85, 141, and 169
    Notes
    [7] - 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: This end-point was related to only serum concentrations after subcutaneous dose of mavrilimumab and hence, not reporting statistics for all the arms in the baseline period.
    End point values
    Mavrilimumab 100 mg
    Number of subjects analysed
    70
    Units: nanogram per milliliter (ng/mL)
    geometric mean (geometric coefficient of variation)
        Baseline (n=69)
    0 ± 512.9
        Day 8 (n=66)
    2837.24 ± 49.1
        Day 15 (n=67)
    1084.43 ± 143.6
        Day 29 (n=69)
    2094.7 ± 58.9
        Day 85 (n=67)
    2886.71 ± 64.1
        Day 141 (n=63)
    1731.65 ± 79.3
        Day 169 (n=64)
    1701.13 ± 67.9
    No statistical analyses for this end point

    Secondary: Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Mavrilimumab

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    End point title
    Number of Participants Exhibiting Anti-Drug Antibodies (ADAs) to Mavrilimumab
    End point description
    Immunogenicity assessment included determination of anti-drug (mavrilimumab) antibodies in serum samples. ADA detection measured by using electrochemiluminescence assays. The immunogenicity population included all participants who received at least 1 dose of mavrilimumab and for whom at least one serum sample for immunogenicity testing was available.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 169
    End point values
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Number of subjects analysed
    68
    70
    Units: participants
        number (not applicable)
    3
    3
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to Day 169
    Adverse event reporting additional description
    The safety population included all participants who received any amount of study medication.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Golimumab 50 mg alternating with Placebo
    Reporting group description
    Participants received alternating doses of golimumab 50 mg (Weeks 0, 4, 8, 12, 16, 20, and 24) and placebo matched to mavrilimumab (Weeks 2, 6, 10, 14, 18, and 22) injections subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

    Reporting group title
    Mavrilimumab 100 mg
    Reporting group description
    Participants received mavrilimumab 100 mg injection subcutaneously every 2 weeks for 24 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) through oral or parenteral route.

    Serious adverse events
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 68 (4.41%)
    2 / 70 (2.86%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Investigations
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Parathyroid tumour benign
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Lung disorder
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Vertebrobasilar insufficiency
         subjects affected / exposed
    0 / 68 (0.00%)
    1 / 70 (1.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastroduodenitis
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    1 / 68 (1.47%)
    0 / 70 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    Golimumab 50 mg alternating with Placebo Mavrilimumab 100 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    29 / 68 (42.65%)
    36 / 70 (51.43%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 68 (1.47%)
    3 / 70 (4.29%)
         occurrences all number
    1
    3
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 68 (2.94%)
    0 / 70 (0.00%)
         occurrences all number
    4
    0
    Hepatic enzyme increased
         subjects affected / exposed
    2 / 68 (2.94%)
    3 / 70 (4.29%)
         occurrences all number
    2
    3
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 68 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    2
    Blood and lymphatic system disorders
    Leukocytosis
         subjects affected / exposed
    0 / 68 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    2
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 68 (2.94%)
    3 / 70 (4.29%)
         occurrences all number
    2
    3
    Migraine
         subjects affected / exposed
    0 / 68 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    2
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    2 / 68 (2.94%)
    1 / 70 (1.43%)
         occurrences all number
    2
    1
    Pyrexia
         subjects affected / exposed
    2 / 68 (2.94%)
    0 / 70 (0.00%)
         occurrences all number
    2
    0
    Influenza like illness
         subjects affected / exposed
    0 / 68 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    3
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 68 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    2
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 68 (1.47%)
    1 / 70 (1.43%)
         occurrences all number
    1
    1
    Nausea
         subjects affected / exposed
    1 / 68 (1.47%)
    1 / 70 (1.43%)
         occurrences all number
    2
    1
    Skin and subcutaneous tissue disorders
    Ecchymosis
         subjects affected / exposed
    1 / 68 (1.47%)
    1 / 70 (1.43%)
         occurrences all number
    1
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 68 (2.94%)
    2 / 70 (2.86%)
         occurrences all number
    3
    2
    Arthralgia
         subjects affected / exposed
    1 / 68 (1.47%)
    1 / 70 (1.43%)
         occurrences all number
    1
    1
    Rheumatoid arthritis
         subjects affected / exposed
    2 / 68 (2.94%)
    1 / 70 (1.43%)
         occurrences all number
    7
    1
    Tendonitis
         subjects affected / exposed
    2 / 68 (2.94%)
    0 / 70 (0.00%)
         occurrences all number
    2
    0
    Metabolism and nutrition disorders
    Dyslipidaemia
         subjects affected / exposed
    2 / 68 (2.94%)
    0 / 70 (0.00%)
         occurrences all number
    2
    0
    Hypercholesterolaemia
         subjects affected / exposed
    2 / 68 (2.94%)
    0 / 70 (0.00%)
         occurrences all number
    2
    0
    Infections and infestations
    Ear infection
         subjects affected / exposed
    1 / 68 (1.47%)
    1 / 70 (1.43%)
         occurrences all number
    1
    1
    Bronchitis
         subjects affected / exposed
    1 / 68 (1.47%)
    1 / 70 (1.43%)
         occurrences all number
    1
    1
    Herpes simplex
         subjects affected / exposed
    0 / 68 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    2
    Influenza
         subjects affected / exposed
    1 / 68 (1.47%)
    1 / 70 (1.43%)
         occurrences all number
    1
    1
    Oral herpes
         subjects affected / exposed
    0 / 68 (0.00%)
    2 / 70 (2.86%)
         occurrences all number
    0
    2
    Nasopharyngitis
         subjects affected / exposed
    1 / 68 (1.47%)
    4 / 70 (5.71%)
         occurrences all number
    1
    4
    Pharyngitis
         subjects affected / exposed
    2 / 68 (2.94%)
    1 / 70 (1.43%)
         occurrences all number
    2
    1
    Rhinitis
         subjects affected / exposed
    2 / 68 (2.94%)
    1 / 70 (1.43%)
         occurrences all number
    2
    1
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 68 (2.94%)
    3 / 70 (4.29%)
         occurrences all number
    3
    4
    Urinary tract infection
         subjects affected / exposed
    1 / 68 (1.47%)
    2 / 70 (2.86%)
         occurrences all number
    1
    2
    Viral upper respiratory tract infection
         subjects affected / exposed
    2 / 68 (2.94%)
    3 / 70 (4.29%)
         occurrences all number
    2
    3

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Dec 2012
    The maximum duration of the study was corrected from 40 weeks to 44 weeks. A diffusing capacity for carbon monoxide (DLCO) assessment was added to the protocol. The need for a sample collection for anti-drug antibodies (ADA) analysis in the event of a severe hypersensitivity reaction was removed from the protocol. A section describing un-blinding in the event of a suspected unexpected serious adverse reaction (SUSAR) was added to the protocol. Reference to the data safety monitoring board (DSMB) was removed from the Study-stopping Criteria section of the protocol. In the case of a clinically significant pulmonary abnormality, the language in the protocol was clarified to make it clear that the investigator was the responsible person, in collaboration with the sponsor, to make the decision to resume administration of investigational product. Exploratory end-point for the evaluation of flow cytometry was removed. Clarification for tuberculosis (TB) test was given if result of the QuantiFERON-TB Gold Test was indeterminate.
    06 Feb 2013
    Forced expiratory volume in 6 seconds (FEV6) assessment was added.
    13 Jun 2013
    Clinical study population was broadened to include subjects with an inadequate response to one or more conventional disease-modifying anti-rheumatic drugs (DMARDs) and anti- tumor necrosis factor (TNF) agents, clarification of forced vital capacity (FVC) was given as part of the diffusing capacity for carbon monoxide (DLCO) assessment.

    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.
    Non-compartmental analyses was not performed for pharmacokinetics parameters due to limited sampling schedule.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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