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   38178   clinical trials with a EudraCT protocol, of which   6270   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:
    Switch To RItuXimab in MS extension An extension study of STRIX-MS - a phase 2 open label study of Rituximab in MS patients previously treated with self-injectibles using a target based therapy approach

    Summary
    EudraCT number
    2013-002378-26
    Trial protocol
    SE  
    Global end of trial date
    12 Apr 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    07 Oct 2018
    First version publication date
    07 Oct 2018
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    STRIX-MSext001
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    County council of Västerbotten
    Sponsor organisation address
    University Hospital of Umeå, Umeå, Sweden, 90185
    Public contact
    Anders Svenningsson, Dept of Neurology, University Hospital of Umeå, Umeå, Sweden, anders.svenningsson@ki.se
    Scientific contact
    Anders Svenningsson, Dept of Neurology, University Hospital of Umeå, Umeå, Sweden, +46 702415852, anders.svenningsson@ki.se
    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
    16 Sep 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    12 Apr 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Apr 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives of the study are •To evaluate the efficiency on inflammatory parameters and the need of retreat-ment to keep a stable condition during long-term treatment with Rituximab in a co-hort of RRMS patients that otherwise would have been treated with first-line MS medications. The inflammatory parameters studied are new relapses and new T2- and Gd-enhancing lesions on MRI. •To study the development of neurodegenerative processes during long-term treatment with Rituximab using quantitative MRI measurements and analysis of bi-omarkers for axonal damage in the cerebrospinal fluid (CSF). These values will be compared with age-matched healthy controls and, when applicable, with values be-fore start of Rituximab treatment.
    Protection of trial subjects
    MRI was be done every 12 months during the whole extension study. Lumbar puncture was performed in close connection to the MRI examinations, as an optional exploratory study. The Rituximab therapy was performed as on an outpatient basis and required approximately 6 hours per infusion. In this extension study, two protocols was used for the long-term treatment of the patients based on patient age and possible inflammatory activity during the initial study (EudraCT 2010-023021-38). Patients treatead according to Protocol no 1 was switched to Protocol no 2 if there was documented disease activity that fulfilled the criteria of “treatment failure” in the study procotol. Patients treated according to Protocol no 2 was offered alternative treatment if there was documented disease activity that fulfilled the criteria of “treatment failure” in the study protocol. Treatment failure definition, in this study, as occurrence of ANY of the below: 1. Any documented relapse activity during the extension study 2. Any documented Gd+ lesion on MRI during the extension study 3. More than one new or enlarging T2 lesion on MRI during the preceding year in the extension study Tests during the study: Blood chemistry (Safety) Flow cytometry (Safety, exploratory) MRI, standard + qMRI (Safety, neurodegeneration) LP (optional exploratory) (Biomarkers, neurodegeneration)
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    04 Nov 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Sweden: 66
    Worldwide total number of subjects
    66
    EEA total number of subjects
    66
    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)
    66
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Inclusion criteria for this extension study: • Have completed the STRIX-MS trial (Eudra-CT 2010-023021-38). • Willing to comply with study procedures • In fertile females, willing to comply with effective contraceptive methods. These include birthcontrol pills, surgical sterilization

    Pre-assignment
    Screening details
    Patients included in the STRIX-MS trial were offered to continue with additional Rituximab courses in the form of this extension study.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Active treatment with Rituximab
    Arm description
    Protocol no 1, assumed low inflammatory disease: Rituximab 500 mg at time 0, 6 and 12 months, thereafter only if indicated from the definition of “treatment failure” below. Protocol no 2, assumed more active inflammatory disease: Rituximab 1000 mg at time 0, 6 and 12 months, thereafter yearly (time 24 and 36 months)
    Arm type
    Experimental

    Investigational medicinal product name
    Rituximab (Mabthera)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Protocol no 1, assumed low inflammatory disease: Rituximab 500 mg at time 0, 6 and 12 months, thereafter only if indicated from the definition of “treatment failure”. Protocol no 2, assumed more active inflammatory disease: Rituximab 1000 mg at time 0, 6 and 12 months, thereafter yearly (time 24 and 36 months)

    Number of subjects in period 1
    Active treatment with Rituximab
    Started
    66
    Completed
    59
    Not completed
    7
         New diagnosis
    1
         Lack of efficacy
    3
         Pregnancy
    1
         Adverse event, non-fatal
    1
         Consent withdrawn by subject
    1

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    Each patient is its own control. There is no comparison between groups.

    Reporting group values
    Overall trial Total
    Number of subjects
    66 66
    Age categorical
    Units: Subjects
        In utero
    0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0
        Newborns (0-27 days)
    0 0
        Infants and toddlers (28 days-23 months)
    0 0
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    66 66
        From 65-84 years
    0 0
        85 years and over
    0 0
    Gender categorical
    Units: Subjects
        Female
    44 44
        Male
    22 22

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Active treatment with Rituximab
    Reporting group description
    Protocol no 1, assumed low inflammatory disease: Rituximab 500 mg at time 0, 6 and 12 months, thereafter only if indicated from the definition of “treatment failure” below. Protocol no 2, assumed more active inflammatory disease: Rituximab 1000 mg at time 0, 6 and 12 months, thereafter yearly (time 24 and 36 months)

    Primary: The proportion of patients undergoing the predefined study protocols over three years that fulfils the criteria free from disease activity

    Close Top of page
    End point title
    The proportion of patients undergoing the predefined study protocols over three years that fulfils the criteria free from disease activity [1]
    End point description
    The proportion of patients undergoing the predefined study protocols over three years that fulfils the criteria “free from disease activity” defined as: o Free from clinical relapse o Free from contrast-enhancing MRI lesions o No more than one new or enlarged MRI lesion visible on T2-weighted images during the previous 12 month period
    End point type
    Primary
    End point timeframe
    The patients were followed up for a period of 3 years.
    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: Each patient is its own control. There is no comparison between treatment groups. All statistical testing will be done as two-sided on a 5 % level of significance, and in particular all confidence intervals (CI) will be 95 % intervals. Test of normality will be performed which will decide as to use parametric (eg Student’s t-test) or non-parametric (eg Wilcoxon rank-sum test) statistic).
    End point values
    Active treatment with Rituximab
    Number of subjects analysed
    59
    Units: Numbers
    59
    No statistical analyses for this end point

    Secondary: The proportion of patients free from all signs of disease activity including, in addi-tion to the primary endpoint, no new T2 lesions during the whole study period and no increase in EDSS.

    Close Top of page
    End point title
    The proportion of patients free from all signs of disease activity including, in addi-tion to the primary endpoint, no new T2 lesions during the whole study period and no increase in EDSS.
    End point description
    The period included in this analysis is from month 0 in the original STRIX-MS study, ie when Rituximab was administered in the first time.
    End point type
    Secondary
    End point timeframe
    The patients were follwoed up for a period of 3 years.
    End point values
    Active treatment with Rituximab
    Number of subjects analysed
    59
    Units: Numbers
    59
    No statistical analyses for this end point

    Secondary: • The degree of brain atrophy development over the course of the whole study peri-od measured as BPF as compared with age-matched healthy controls

    Close Top of page
    End point title
    • The degree of brain atrophy development over the course of the whole study peri-od measured as BPF as compared with age-matched healthy controls
    End point description
    End point type
    Secondary
    End point timeframe
    The patients were followed for a period of 3 years.
    End point values
    Active treatment with Rituximab
    Number of subjects analysed
    59
    Units: Number
    59
    No statistical analyses for this end point

    Secondary: • The levels of Neurofilament-light values in CSF analyses, which will be compared with age-matched healthy controls as well as before Rituximab treatment started.

    Close Top of page
    End point title
    • The levels of Neurofilament-light values in CSF analyses, which will be compared with age-matched healthy controls as well as before Rituximab treatment started.
    End point description
    End point type
    Secondary
    End point timeframe
    The patients were followed 3 years.
    End point values
    Active treatment with Rituximab
    Number of subjects analysed
    59
    Units: Numbers
    59
    No statistical analyses for this end point

    Secondary: • The proportion of patients undergoing the predefined study protocol that because of disease activity will either change therapy or obtain additional Rituximab infu-sions.

    Close Top of page
    End point title
    • The proportion of patients undergoing the predefined study protocol that because of disease activity will either change therapy or obtain additional Rituximab infu-sions.
    End point description
    End point type
    Secondary
    End point timeframe
    The patients were followed for 3 years.
    End point values
    Active treatment with Rituximab
    Number of subjects analysed
    59
    Units: Numbers
    59
    No statistical analyses for this end point

    Secondary: • To document the safety of Rituximab treatment during long-term treatment of RRMS patients with Rituximab using a target based treatment protocol.

    Close Top of page
    End point title
    • To document the safety of Rituximab treatment during long-term treatment of RRMS patients with Rituximab using a target based treatment protocol.
    End point description
    End point type
    Secondary
    End point timeframe
    The patients were followed for 3 years.
    End point values
    Active treatment with Rituximab
    Number of subjects analysed
    59
    Units: Numbers
    59
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From the time a patient consents to participate in the trial until he/she has completed the trial.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Active treatment period
    Reporting group description
    Patients receiving Rituximab according to either protocol no 1 or protocol no 2 : Protocol no 1, assumed low inflammatory disease: Rituximab 500 mg at time 0, 6 and 12 months, thereafter only if indicated from the definition of treatment failure. Protocol no 2, assumed more active inflammatory disease: Rituximab 1000 mg at time 0, 6 and 12 months, thereafter yearly (time 24 and 36 months).

    Serious adverse events
    Active treatment period
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 66 (7.58%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Nervous system disorders
    Migraine with aura
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Parkinson's disease
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Active treatment period
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    50 / 66 (75.76%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 66 (3.03%)
         occurrences all number
    2
    Pregnancy, puerperium and perinatal conditions
    Pregnancy
    Additional description: Healthy baby
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    General disorders and administration site conditions
    Swelling NOS
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Psychiatric disorders
    Anxiety attack
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Insomnia
         subjects affected / exposed
    2 / 66 (3.03%)
         occurrences all number
    3
    Low mood
         subjects affected / exposed
    2 / 66 (3.03%)
         occurrences all number
    2
    Reproductive system and breast disorders
    Erectile dysfunction
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Ovarian function insufficiency
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Injury, poisoning and procedural complications
    Fracture
         subjects affected / exposed
    3 / 66 (4.55%)
         occurrences all number
    4
    Headache post lumbar punction
         subjects affected / exposed
    2 / 66 (3.03%)
         occurrences all number
    2
    Itching
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Olekranon bursitis
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Pain due to intra-uterine coil
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Pain shoulder
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Ferritin increased
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Haemoglobin decreased
         subjects affected / exposed
    2 / 66 (3.03%)
         occurrences all number
    2
    Iron deficiency
         subjects affected / exposed
    2 / 66 (3.03%)
         occurrences all number
    2
    Lipids increased
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    2 / 66 (3.03%)
         occurrences all number
    2
    Headache
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Parkinson's disease
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Speech impairment
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Syncope
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Visual phenomena
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Eye disorders
    Dry eyes
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Acid reflux
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Dry mouth
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Lymphocytic colitis
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    2 / 66 (3.03%)
         occurrences all number
    2
    Skin sores
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Pain
    Additional description: Pain preferred term for all AEs but lower level term: Pain, Pain hand/fingers, Pain joints, extremity, Pain joints/fingers/ankles, Pain knee, Pain leg, Pain neck/shoulder
         subjects affected / exposed
    5 / 66 (7.58%)
         occurrences all number
    7
    Joint swelling
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Gout
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Vitamin B deficiency
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Infections and infestations
    Pharynx itching sensation of
         subjects affected / exposed
    3 / 66 (4.55%)
         occurrences all number
    3
    Borrelia infection
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Bronchial infection
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Cold
         subjects affected / exposed
    10 / 66 (15.15%)
         occurrences all number
    15
    Cough
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Eye infection
         subjects affected / exposed
    2 / 66 (3.03%)
         occurrences all number
    3
    Fever
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Herpes zoster ophthalmicus
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Influenza
         subjects affected / exposed
    3 / 66 (4.55%)
         occurrences all number
    3
    Otitis
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Otosalpingitis
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Ringworm
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Sinusitis
         subjects affected / exposed
    5 / 66 (7.58%)
         occurrences all number
    5
    Sore throat
         subjects affected / exposed
    2 / 66 (3.03%)
         occurrences all number
    2
    Tonsillitis
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    1
    Tooth infection
         subjects affected / exposed
    1 / 66 (1.52%)
         occurrences all number
    2
    Upper respiratory infection
         subjects affected / exposed
    3 / 66 (4.55%)
         occurrences all number
    3
    Urinary tract infection
         subjects affected / exposed
    4 / 66 (6.06%)
         occurrences all number
    6

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    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