Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   37554   clinical trials with a EudraCT protocol, of which   6160   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A 24-week Randomized, Open-Label, Parallel-Group, Active-Controlled, Exploratory, Proof-of-Mechanism Imaging Study Investigating the Efficacy of 150 mg of Namilumab Administered Subcutaneously vs Adalimumab in Patients With Moderate to Severe Early Rheumatoid Arthritis Inadequately Responding to Methotrexate

    Summary
    EudraCT number
    2014-002945-23
    Trial protocol
    GB   CZ   EE   ES  
    Global end of trial date
    03 Nov 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    26 Nov 2017
    First version publication date
    26 Nov 2017
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    MT203-2004
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02393378
    WHO universal trial number (UTN)
    U1111-1160-1791
    Sponsors
    Sponsor organisation name
    Takeda
    Sponsor organisation address
    One Takeda Parkway Deerfield, Unites Sates, United States, IL 60015
    Public contact
    Medical Director, Clinical Science, Takeda, +1 877-825-3327, clinicaltrialregistry@tpna.com
    Scientific contact
    Medical Director, Clinical Science, Takeda, +1 877-825-3327, clinicaltrialregistry@tpna.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
    03 Nov 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Nov 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To explore the effect on structural damage imaging markers measured as change from Baseline in synovitis, erosion, and bone marrow edema (osteitis), in metacarpophalangeal (MCP) joints and wrist at Week 24 on magnetic resonance imaging (MRI) using the RA-MRI scoring Outcome Measures in Rheumatoid Arthritis Clinical Trials (RAMRIS OMERACT).
    Protection of trial subjects
    All study participants were required to read and sign an Informed Consent Form.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    08 Apr 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    5 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Estonia: 3
    Country: Number of subjects enrolled
    Russian Federation: 4
    Worldwide total number of subjects
    7
    EEA total number of subjects
    3
    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)
    4
    From 65 to 84 years
    3
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Participants took part in the study at 5 investigative sites in Estonia and Russian Federation from 08 April 2015 to 03 November 2016.

    Pre-assignment
    Screening details
    Participants with a diagnosis of rheumatoid arthritis were enrolled in 2:1 ratio to receive either namilumab combined with methotrexate (MTX) or adalimumab combined with MTX.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Adalimumab 40 mg
    Arm description
    Adalimumab 40 mg SC injection at Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22 as an add-on to weekly existing stable MTX and folic acid as prescribed in clinical practice.
    Arm type
    Experimental

    Investigational medicinal product name
    Adalimumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received Adalimumab 40 mg SC injection at Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22.

    Arm title
    Namilumab 150 mg
    Arm description
    Namilumab 300 mg SC injection at Week 0 followed by 150 mg SC injection at Weeks 2, 6, 10, 14, 18, and 22 as an add-on to weekly existing stable MTX and folic acid as prescribed in clinical practice.
    Arm type
    Active comparator

    Investigational medicinal product name
    Namilumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received Namilumab 300 mg SC injection at Week 0 followed by 150 mg SC injection at Weeks 2, 6, 10, 14, 18, and 22.

    Number of subjects in period 1
    Adalimumab 40 mg Namilumab 150 mg
    Started
    3
    4
    Completed
    3
    4

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Adalimumab 40 mg
    Reporting group description
    Adalimumab 40 mg SC injection at Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22 as an add-on to weekly existing stable MTX and folic acid as prescribed in clinical practice.

    Reporting group title
    Namilumab 150 mg
    Reporting group description
    Namilumab 300 mg SC injection at Week 0 followed by 150 mg SC injection at Weeks 2, 6, 10, 14, 18, and 22 as an add-on to weekly existing stable MTX and folic acid as prescribed in clinical practice.

    Reporting group values
    Adalimumab 40 mg Namilumab 150 mg Total
    Number of subjects
    3 4 7
    Age Categorical
    Units: Subjects
        45 to 64 years
    1 3 4
        >= 65 years
    2 1 3
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    63.0 ± 7.21 61.3 ± 6.90 -
    Gender, Male/Female
    Units: Subjects
        Female
    2 0 2
        Male
    1 4 5
    Race/Ethnicity, Customized
    Units: Subjects
        White
    3 4 7
    Body Mass Index (BMI) Categories
    Units: Subjects
        < 30 kg/m^2
    1 2 3
        >= 30 kg/m^2
    2 2 4
    Region of Enrollment
    Units: Subjects
        Estonia
    1 2 3
        Russia
    2 2 4
    Study Specific Characteristic | Height
    Units: cm
        arithmetic mean (standard deviation)
    171.7 ± 8.96 162.5 ± 3.00 -
    Study Specific Characteristic | Weight
    Units: kg
        arithmetic mean (standard deviation)
    106.67 ± 16.197 78.83 ± 16.550 -
    Study Specific Characteristic | Body Mass Index (BMI)
    BMI = Weight in kg/Height in square meters.
    Units: kg/m^2
        arithmetic mean (standard deviation)
    36.77 ± 8.806 29.68 ± 5.844 -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Adalimumab 40 mg
    Reporting group description
    Adalimumab 40 mg SC injection at Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22 as an add-on to weekly existing stable MTX and folic acid as prescribed in clinical practice.

    Reporting group title
    Namilumab 150 mg
    Reporting group description
    Namilumab 300 mg SC injection at Week 0 followed by 150 mg SC injection at Weeks 2, 6, 10, 14, 18, and 22 as an add-on to weekly existing stable MTX and folic acid as prescribed in clinical practice.

    Primary: Change from Baseline in Synovitis, Erosion and Bone Marrow Edema (Osteitis) Score at Week 24

    Close Top of page
    End point title
    Change from Baseline in Synovitis, Erosion and Bone Marrow Edema (Osteitis) Score at Week 24 [1]
    End point description
    A Magnetic Resonance Imaging (MRI) of Metacarpophalangeal (MCP) and Wrist of the dominant hand was performed at the baseline and at week 24. Change from the Baseline was assessed according to the Outcome Measures in Rheumatoid Arthritis (RA) Clinical Trials RA-MRI scoring (OMERACT RAMRIS) Standard. RAMRIS score is the sum of its core components: Synovitis Score, Edema Score, and Erosion Score. Synovitis is scored from 0 (normal) to 9 (maximum distension of synovial cavity). Edema is scored 0 (normal) to 69 (maximum articular bone involvement). Erosion is scored from 0 (normal) to 230 (maximum erosion of articular bone). Total RAMRIS score=0 (normal), maximum RAMRIS score=308 (severe structural damage). For Synovial Score, Edema Score, Erosion Score, and RAMRIS score, increasing number = increasing severity. Full analysis set included participants who received at least one dose of study medication. Here 'n' is the number of participants who were evaluated for specific sub-score.
    End point type
    Primary
    End point timeframe
    Baseline and Week 24
    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: Statistical analysis was not assessed for this endpoint.
    End point values
    Adalimumab 40 mg Namilumab 150 mg
    Number of subjects analysed
    3
    4
    Units: score on a scale
    arithmetic mean (standard deviation)
        Erosion Score, Change at Week 24 (n=3,3)
    0.50 ± 0.866
    0.00 ± 0.500
        Synovitis Score, Change at Week 24 (n=3,3)
    0.17 ± 0.764
    -1.50 ± 4.770
        Osteitis Score, Change at Week 24 (n=3,2)
    -0.33 ± 0.764
    -2.00 ± 3.536
    No statistical analyses for this end point

    Secondary: Change from Baseline in Dynamic Contrast-enhanced - Magnetic Resonance Imaging (DCE-MRI) Parameters at Week 24

    Close Top of page
    End point title
    Change from Baseline in Dynamic Contrast-enhanced - Magnetic Resonance Imaging (DCE-MRI) Parameters at Week 24
    End point description
    DCE-MRI was used to measure synovial vascular perfusion. The change from baseline in DCE-MRI parameters of synovial vascular perfusion at Week 24 were measured. Full analysis set included participants who received at least one dose of study medication. Hence, number of participants analyzed (N) is the participants who were evaluated for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 24
    End point values
    Adalimumab 40 mg Namilumab 150 mg
    Number of subjects analysed
    3
    3
    Units: mL
        arithmetic mean (standard deviation)
    0.016 ± 0.0253
    -0.052 ± 0.0662
    No statistical analyses for this end point

    Secondary: Number of Participants who Achieved Remission at Week 24

    Close Top of page
    End point title
    Number of Participants who Achieved Remission at Week 24
    End point description
    Remission is defined as percentage of participants who achieved Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) score <2.6. DAS28-CRP is a composite measure of inflammation in rheumatoid arthritis (RA) and incorporates a tender and swollen joint count, CRP and patient global assessment of disease activity expressed in a gaussian distribution of variables ranging from 0 to 10. A DAS28-CRP score of <3.2 = low level of disease activity, while a score of >5.1 = high level of disease activity. Using DAS-CRP as a continuous scale allows investigators (and clinicians) to measure a clinically meaningful endpoint following institution of a therapeutic intervention. In RA, clinical remission would therefore be graded as a DAS28 score of ≤2.6 with disease flare accompanying scores of ≥5.1; well-controlled disease is best characterized as fitting in between these two scores. Full analysis set included participants who received at least one dose of study medication.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Adalimumab 40 mg Namilumab 150 mg
    Number of subjects analysed
    3
    4
    Units: participants
    0
    2
    No statistical analyses for this end point

    Secondary: Number of Participants who Achieved Low Disease Activity at Week 24

    Close Top of page
    End point title
    Number of Participants who Achieved Low Disease Activity at Week 24
    End point description
    Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) low disease activity is defined as a score <3.2. The DAS28-CRP is a composite measure of inflammation in RA and incorporates a tender and swollen joint count, CRP and patient global assessment of disease activity expressed in a gaussian distribution of variables ranging from 0 to 10. A DAS28-CRP score of <3.2 suggests a low level of disease activity, while a score of >5.1 suggests a high level of disease activity. Using the DAS-CRP as a continuous scale allows investigators (and clinicians) to measure a clinically meaningful endpoint following institution of a therapeutic intervention. In RA, clinical remission would therefore be graded as a DAS28 score of ≤2.6 with disease flare accompanying scores of ≥5.1; well-controlled disease is best characterized as fitting in between these two scores. Full analysis set included participants who received at least one dose of study medication.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Adalimumab 40 mg Namilumab 150 mg
    Number of subjects analysed
    3
    4
    Units: participants
    2
    4
    No statistical analyses for this end point

    Secondary: Percentage of Participants who Achieved ACR 20, 50, and 70 at Week 24

    Close Top of page
    End point title
    Percentage of Participants who Achieved ACR 20, 50, and 70 at Week 24
    End point description
    The American College of Rheumatology (ACR) 20 is composite index of improvement in RA proposed by the ACR. ACR20 refers to a composite improvement of 20% in swollen joint count, tender joint count, and 3 or more of the following 5 measures: Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, Patient Pain VAS, Patient's self-addressed disability (HAQ), Acute-phase reactant (ESR or CRP) The ACR 50 and ACR 70 are similar tools, used to indicate 50% and 70% improvement, respectively. Full analysis set included participants who received at least one dose of study medication.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Adalimumab 40 mg Namilumab 150 mg
    Number of subjects analysed
    3
    4
    Units: percentage of participants
        ACR 20
    2
    4
        ACR 50
    2
    3
        ACR 70
    1
    2
    No statistical analyses for this end point

    Secondary: Change from Baseline in DAS28-CRP

    Close Top of page
    End point title
    Change from Baseline in DAS28-CRP
    End point description
    The DAS28-CRP is a composite measure of inflammation in RA and incorporates a tender and swollen joint count, CRP and patient global assessment of disease activity expressed in a gaussian distribution of variables ranging from 0 to 10. A DAS28-CRP score of <3.2 suggests a low level of disease activity, while a score of >5.1 suggests a high level of disease activity. Using the DAS-CRP as a continuous scale allows investigators (and clinicians) to measure a clinically meaningful endpoint following institution of a therapeutic intervention. In RA, clinical remission would therefore be graded as a DAS28 score of ≤3.2 with disease flare accompanying scores of ≥5.1; well-controlled disease is best characterized as fitting in between these two scores. Full analysis set included participants who received at least one dose of study medication. Here 'n' is the number of participants who were evaluated at specific time point.
    End point type
    Secondary
    End point timeframe
    Baseline Up to Week 42
    End point values
    Adalimumab 40 mg Namilumab 150 mg
    Number of subjects analysed
    3
    4
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 2 (n =2,3)
    -0.55 ± 0.737
    -0.78 ± 0.333
        Week 6 (n =3,4)
    -1.36 ± 1.086
    -1.58 ± 0.494
        Week 10 (n =2,4)
    -1.74 ± 1.103
    -1.83 ± 0.344
        Week 12 (n =3,4)
    -1.94 ± 1.036
    -2.12 ± 0.613
        Week 18 (n =3,4)
    -2.05 ± 1.136
    -2.72 ± 0.486
        Week 24 (n =3,4)
    -2.04 ± 1.596
    -2.99 ± 0.216
        Week 32 (n =3,4)
    -1.89 ± 1.946
    -2.38 ± 0.862
        Week 42 (n =3,4)
    -1.99 ± 1.938
    -1.57 ± 1.387
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to Week 42
    Adverse event reporting additional description
    At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Namilumab 150 mg
    Reporting group description
    Namilumab 300 mg SC injection at Week 0 followed by 150 mg SC injection at Weeks 2, 6, 10, 14, 18, and 22 as an add-on to weekly existing stable MTX and folic acid as prescribed in clinical practice.

    Reporting group title
    Adalimumab 40 mg
    Reporting group description
    Adalimumab 40 mg SC injection at Weeks 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 22 as an add-on to weekly existing stable MTX and folic acid as prescribed in clinical practice.

    Serious adverse events
    Namilumab 150 mg Adalimumab 40 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Infections and infestations
    Cellulitis streptococcal
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Namilumab 150 mg Adalimumab 40 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 4 (100.00%)
    3 / 3 (100.00%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Forced expiratory volume decreased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Forced vital capacity decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    Neutrophil count decreased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    Nervous system disorders
    Syncope
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Panic attack
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Joint swelling
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Streptococcal sepsis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 3 (33.33%)
         occurrences all number
    1
    1

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Apr 2015
    • Clarified of inclusion and exclusion criteria. • Increased of the screening period from 4 weeks to 8 weeks. • Added flexibility around scheduling assessments at each visit. Allowing visits to be performed over two consecutive days. • Revised contraceptive advice.
    11 Feb 2016
    • Updated to the inclusion criteria about onset of early rheumatoid arthritis (RA). • Updated to exclusion criteria around lung function and management of associated adverse events. • Updated to the pulmonary alvelolar proteinosis (PAP) language. • Clarified and updated: Schedule of Study Procedures. • Results of the new 26-week monkey study and calculation of the new safety margin added. • Takeda made the strategic decision to stop the TELLUS study on 18 December 2015 but allow all the patients already enrolled to complete all the assessments as per protocol. The sample size and the number of sites are consequently reduced to match the recruitment status at the time of the decision.

    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
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA