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   41189   clinical trials with a EudraCT protocol, of which   6743   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
    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 3-Year Open-Label, Exploratory, Single Arm Study to Describe Long Term Changes in the Visual System of Patients with Relapsing Remitting Multiple Sclerosis (RRMS) on Oral Dimethyl Fumarate

    Summary
    EudraCT number
    2014-000395-26
    Trial protocol
    DE  
    Global end of trial date
    21 Oct 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    08 Dec 2017
    First version publication date
    08 Dec 2017
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    GER-BGT-13-10586
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Biogen
    Sponsor organisation address
    250 Binney Street, Cambridge, United States, 02142
    Public contact
    Study Director, Biogen, +1 866-633-4636, clinicaltrials@biogen.com
    Scientific contact
    Study Director, Biogen, +1 866-633-4636, clinicaltrials@biogen.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    12 Oct 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    21 Oct 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Oct 2016
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate changes of the visual system in relapsed remitting multiple sclerosis (RRMS) patients treated with dimethyl fumarate assessed by retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) over 36 months.
    Protection of trial subjects
    Written informed consent was obtained from each subject prior to evaluations performed for eligibility. Subjects were given adequate time to review the information in the informed consent and were allowed to ask, and have answered, questions concerning all portions of the conduct of the study. Subjects were provided with a copy of the signed and dated informed consent form (ICF).
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    02 Nov 2015
    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
    Germany: 18
    Worldwide total number of subjects
    18
    EEA total number of subjects
    18
    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)
    18
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Subjects were recruited from 5 sites in Germany. All subjects who signed the informed consent form and who were initially considered for study participation must have been clinically stable on 240 mg dimethyl fumarate (DMF) twice daily for at least 4 and up to 20 weeks prior to the screening visit.

    Pre-assignment
    Screening details
    Subjects were screened for enrollment over 28 days. All screened subjects were exposed to dimethyl fumarate (DMF) for at least one day (at screening) during the study. Subjects deemed screening failures were exposed to DMF for one day (at screening) except for one subject that was on DMF for 86 days and was retrospectively deemed screening failure.

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

    Arms
    Arm title
    Dimethyl Fumarate
    Arm description
    Adult subjects who met eligibility criteria and with a confirmed diagnosis of relapsed remitting multiple sclerosis (RRMS) defined by the current McDonald criteria and be in line with the Tecfidera® summary of product characteristics.
    Arm type
    Experimental

    Investigational medicinal product name
    Dimethyl Fumarate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Administered as specified in the treatment arm.

    Number of subjects in period 1 [1]
    Dimethyl Fumarate
    Started
    12
    Completed
    12
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Not all subjects who signed an informed consent form and who were screened for eligibility contributed data to the baseline characteristics and study endpoints.

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Dimethyl Fumarate
    Reporting group description
    Adult subjects who met eligibility criteria and with a confirmed diagnosis of relapsed remitting multiple sclerosis (RRMS) defined by the current McDonald criteria and be in line with the Tecfidera® summary of product characteristics.

    Reporting group values
    Dimethyl Fumarate Total
    Number of subjects
    12 12
    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)
    12 12
        From 65-84 years
    0 0
        85 years and over
    0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    37.4 ± 10.3 -
    Gender Categorical
    Units: Subjects
        Female
    8 8
        Male
    4 4

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Dimethyl Fumarate
    Reporting group description
    Adult subjects who met eligibility criteria and with a confirmed diagnosis of relapsed remitting multiple sclerosis (RRMS) defined by the current McDonald criteria and be in line with the Tecfidera® summary of product characteristics.

    Primary: Change from baseline in mean global thickness of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters

    Close Top of page
    End point title
    Change from baseline in mean global thickness of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters [1]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -0.13 ± 3.14
        Right Eye
    0.38 ± 1.93
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the papillo macular bundle of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the papillo macular bundle of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters [2]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 millimeters (mm), 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo-macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [2] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    1.0 ± 2.2
        Right Eye
    0.1 ± 1.4
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the nasal/superior quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the nasal/superior quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters [3]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [3] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -2.3 ± 7.6
        Right Eye
    -0.1 ± 3.6
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the nasal quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the nasal quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters [4]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [4] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -0.3 ± 2.5
        Right Eye
    0.9 ± 3.6
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the nasal/inferior quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the nasal/inferior quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters [5]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [5] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    1.6 ± 4.1
        Right Eye
    -0.5 ± 2.9
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the temporal/inferior quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the temporal/inferior quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters [6]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [6] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    1.9 ± 6.8
        Right Eye
    -0.5 ± 1.0
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the temporal quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the temporal quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters [7]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [7] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -0.5 ± 2.2
        Right Eye
    0.4 ± 1.4
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the temporal/superior quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the temporal/superior quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters [8]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [8] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -0.4 ± 4.2
        Right Eye
    1.0 ± 1.8
    No statistical analyses for this end point

    Primary: Change from baseline in the ratio of the mean thickness of the nasal and temporal quadrants of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters

    Close Top of page
    End point title
    Change from baseline in the ratio of the mean thickness of the nasal and temporal quadrants of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 3.5 millimeters [9]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [9] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    0.001 ± 0.041
        Right Eye
    0.006 ± 0.042
    No statistical analyses for this end point

    Primary: Change from baseline in mean global thickness of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in mean global thickness of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [10]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [10] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -0.71 ± 2.37
    No statistical analyses for this end point

    Primary: Change from baseline in mean global thickness of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in mean global thickness of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [11]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [11] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Right Eye
    0.25 ± 1.85
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the papillo macular bundle of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the papillo macular bundle of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [12]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [12] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -0.4 ± 1.0
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the papillo macular bundle of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the papillo macular bundle of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [13]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [13] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Right Eye
    1.1 ± 2.5
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the nasal/superior quadrant of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the nasal/superior quadrant of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [14]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [14] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -1.0 ± 5.0
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the nasal/superior quadrant of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the nasal/superior quadrant of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [15]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [15] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Right Eye
    0.4 ± 2.5
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the nasal quadrant of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the nasal quadrant of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [16]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [16] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -0.9 ± 2.4
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the nasal quadrant of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the nasal quadrant of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [17]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [17] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Right Eye
    0.8 ± 2.9
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the nasal/inferior quadrant of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the nasal/inferior quadrant of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [18]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [18] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    0.6 ± 2.1
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the nasal/inferior quadrant of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the nasal/inferior quadrant of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [19]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [19] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Right Eye
    0.4 ± 3.1
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the temporal/inferior quadrant of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the temporal/inferior quadrant of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [20]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [20] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -0.7 ± 3.0
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the temporal/inferior quadrant of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the temporal/inferior quadrant of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [21]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [21] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Right Eye
    -0.4 ± 1.7
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the temporal quadrant of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the temporal quadrant of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [22]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [22] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -0.6 ± 1.8
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the temporal quadrant of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the temporal quadrant of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [23]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [23] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Right Eye
    -0.5 ± 3.5
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the temporal/superior quadrant of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the temporal/superior quadrant of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [24]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [24] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -0.9 ± 4.2
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the temporal/superior quadrant of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the temporal/superior quadrant of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [25]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [25] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Right Eye
    -1.9 ± 5.0
    No statistical analyses for this end point

    Primary: Change from baseline in the ratio of the mean thickness of the nasal and temporal quadrants of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in the ratio of the mean thickness of the nasal and temporal quadrants of the retinal nerve fiber layer in the left eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [26]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [26] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -0.003 ± 0.036
    No statistical analyses for this end point

    Primary: Change from baseline in the ratio of the mean thickness of the nasal and temporal quadrants of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters

    Close Top of page
    End point title
    Change from baseline in the ratio of the mean thickness of the nasal and temporal quadrants of the retinal nerve fiber layer in the right eye as measured by optical coherence tomography at a circle diameter of 4.1 millimeters [27]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [27] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    8
    Units: micrometers
    arithmetic mean (standard deviation)
        Right Eye
    0.029 ± 0.088
    No statistical analyses for this end point

    Primary: Change from baseline in mean global thickness of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7 millimeters

    Close Top of page
    End point title
    Change from baseline in mean global thickness of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7 millimeters [28]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [28] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -0.14 ± 0.99
        Right Eye
    0.29 ± 2.91
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the papillo macular bundle of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the papillo macular bundle of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7 millimeters [29]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [29] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    0.4 ± 1.8
        Right Eye
    1.3 ± 2.7
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the nasal/superior quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the nasal/superior quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7 millimeters [30]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [30] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    0.9 ± 2.5
        Right Eye
    -0.1 ± 3.0
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the nasal quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7

    Close Top of page
    End point title
    Change from baseline in mean thickness of the nasal quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7 [31]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT).The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [31] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -1.0 ± 2.3
        Right Eye
    0.1 ± 2.9
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the nasal/inferior quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the nasal/inferior quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7 millimeters [32]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [32] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    1.0 ± 1.8
        Right Eye
    0.0 ± 6.0
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the temporal/inferior quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the temporal/inferior quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7 millimeters [33]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [33] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -0.3 ± 2.1
        Right Eye
    -0.4 ± 3.2
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the temporal quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the temporal quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7 millimeters [34]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [34] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -0.1 ± 0.6
        Right Eye
    0.9 ± 2.2
    No statistical analyses for this end point

    Primary: Change from baseline in mean thickness of the temporal/superior quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7 millimeters

    Close Top of page
    End point title
    Change from baseline in mean thickness of the temporal/superior quadrant of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7 millimeters [35]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    Baseline and End-of-Study
    Notes
    [35] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: micrometers
    arithmetic mean (standard deviation)
        Left Eye
    -0.4 ± 1.8
        Right Eye
    -1.1 ± 3.0
    No statistical analyses for this end point

    Primary: Change from baseline in the ratio of the mean thickness of the nasal and temporal quadrants of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7 millimeters

    Close Top of page
    End point title
    Change from baseline in the ratio of the mean thickness of the nasal and temporal quadrants of the retinal nerve fiber layer as measured by optical coherence tomography at a circle diameter of 4.7 millimeters [36]
    End point description
    Changes in retinal nerve fiber layer (RNFL) thickness were measured for both eyes at baseline and at the end of the study by using Heidelberg spectral domain (SD) optical coherence tomography (OCT). The mean duration between baseline and end-of-study assessments was 21.8±10.5 weeks (median: 17.5 weeks [range: 12.7; 46.3 weeks]). OCT scans were performed at circle diameters of 3.5 mm, 4.1 mm, and 4.7 mm. Thickness was measured globally, for the papillo macular bundle, and for the nasal, nasal/inferior, temporal/inferior, temporal, temporal/superior, and nasal/superior quadrants. In addition, the nasal/temporal ratio was calculated. A negative change from baseline indicates that retinal thickness decreased. This outcome assessed the Full Analysis Set, defined as all enrolled patients who were successfully screened (i.e. met all eligibility criteria) and who had post-baseline measurements available.
    End point type
    Primary
    End point timeframe
    micrometers
    Notes
    [36] - 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: Although it is generally expected that each primary endpoint will have at least one statistical analysis, statistical analyses were not performed because the study was terminated early.
    End point values
    Dimethyl Fumarate
    Number of subjects analysed
    7
    Units: Baseline and End-of-Study
    arithmetic mean (standard deviation)
        Left Eye
    -0.017 ± 0.049
        Right Eye
    0.001 ± 0.052
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Screening to End-of-Study; maximum 50.3 weeks
    Adverse event reporting additional description
    The mean time of study participation of the safety population from screening to End-of-Study was 14.0±13.2 weeks (median: 13.1 weeks; [range: 0.1; 50.3]).
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Safety Population
    Reporting group description
    All enrolled subjects who received dimethyl fumarate (DMF) are included in safety population. As eligible subjects must have been treated with 240 mg DMF twice daily for at least four weeks and up to 20 weeks prior to screening, all enrolled subjects (i.e. with a signed informed consent form) were included in the safety population.

    Serious adverse events
    Safety Population
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 18 (5.56%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Nervous system disorders
    Optic neuritis
         subjects affected / exposed
    1 / 18 (5.56%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Safety Population
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 18 (33.33%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    1 / 18 (5.56%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 18 (5.56%)
         occurrences all number
    1
    Nervous system disorders
    Cervicogenic headache
         subjects affected / exposed
    1 / 18 (5.56%)
         occurrences all number
    1
    Hypoaesthesia
         subjects affected / exposed
    1 / 18 (5.56%)
         occurrences all number
    2
    Multiple sclerosis relapse
         subjects affected / exposed
    1 / 18 (5.56%)
         occurrences all number
    1
    Somnolence
         subjects affected / exposed
    1 / 18 (5.56%)
         occurrences all number
    1
    Paraesthesia
         subjects affected / exposed
    1 / 18 (5.56%)
         occurrences all number
    2
    General disorders and administration site conditions
    Facial pain
         subjects affected / exposed
    1 / 18 (5.56%)
         occurrences all number
    1
    Gastrointestinal disorders
    Dyspepsia
         subjects affected / exposed
    1 / 18 (5.56%)
         occurrences all number
    2
    Haemorrhoids thrombosed
         subjects affected / exposed
    1 / 18 (5.56%)
         occurrences all number
    1
    Renal and urinary disorders
    Micturition urgency
         subjects affected / exposed
    1 / 18 (5.56%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Temporomandibular joint syndrome
         subjects affected / exposed
    1 / 18 (5.56%)
         occurrences all number
    1
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    1 / 18 (5.56%)
         occurrences all number
    1

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 May 2014
    The amendment included the following main changes: Protocol amendment to further define and specify the objectives and parameters of the clinical trial. The description of statistical analysis was edited. The exclusion criteria as well as study stopping rules were amended, the specifications for pregnancy testing were enhanced and some inconsistencies within the protocol were clarified.
    07 Jul 2015
    The amendment was triggered by the Ethic Committee review and included the following changes of the protocol: study title, the primary outcome, primary endpoint, exclusion criteria, primary contact point, and optical coherence tomography section.
    10 May 2016
    The amendment included the following changes of the protocol: primary contact point, lymphocyte monitoring, adding PLM information to the profile of previous experience, exclusion criteria, discontinuation of the Study treatment, and pregnancy section.

    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.
    This study was terminated early, and the number of subjects who participated was low. As such, the data reported here may not be suitable to draw conclusions regarding the outcomes of the study.
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    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
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA