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
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Summary
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EudraCT number |
2014-000395-26 |
Trial protocol |
DE |
Global end of trial date |
21 Oct 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Dec 2017
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First version publication date |
08 Dec 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GER-BGT-13-10586
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Biogen
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Sponsor organisation address |
250 Binney Street, Cambridge, United States, 02142
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Public contact |
Study Director, Biogen, +1 866-633-4636, clinicaltrials@biogen.com
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Scientific contact |
Study Director, Biogen, +1 866-633-4636, clinicaltrials@biogen.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
12 Oct 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Oct 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Oct 2016
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Was the trial ended prematurely? |
Yes
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General information about the trial
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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.
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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).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Nov 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 18
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Worldwide total number of subjects |
18
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EEA total number of subjects |
18
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
18
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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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. | ||||||
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Pre-assignment
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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. | ||||||
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Period 1
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Period 1 title |
Overall Period
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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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
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Administered as specified in the treatment arm.
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| 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. |
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Baseline characteristics reporting groups
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Reporting group title |
Dimethyl Fumarate
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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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Dimethyl Fumarate
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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. | ||
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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.
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End point type |
Primary
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End point timeframe |
Baseline and End-of-Study
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| 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. |
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| No statistical analyses for this end point | |||||||||||||
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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.
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End point type |
Primary
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End point timeframe |
Baseline and End-of-Study
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| 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. |
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| No statistical analyses for this end point | |||||||||||||
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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.
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End point type |
Primary
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End point timeframe |
Baseline and End-of-Study
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| 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. |
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| No statistical analyses for this end point | |||||||||||||
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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.
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End point type |
Primary
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End point timeframe |
Baseline and End-of-Study
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| 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. |
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| No statistical analyses for this end point | |||||||||||||
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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.
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End point type |
Primary
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End point timeframe |
Baseline and End-of-Study
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| 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. |
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| No statistical analyses for this end point | |||||||||||||
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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.
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End point type |
Primary
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End point timeframe |
Baseline and End-of-Study
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| 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. |
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| No statistical analyses for this end point | |||||||||||||
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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.
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End point type |
Primary
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End point timeframe |
Baseline and End-of-Study
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| 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. |
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| No statistical analyses for this end point | |||||||||||||
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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.
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End point type |
Primary
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End point timeframe |
Baseline and End-of-Study
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| 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. |
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| No statistical analyses for this end point | |||||||||||||
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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.
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End point type |
Primary
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End point timeframe |
Baseline and End-of-Study
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| 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. |
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| No statistical analyses for this end point | |||||||||||||
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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.
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End point type |
Primary
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End point timeframe |
Baseline and End-of-Study
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| 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. |
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| No statistical analyses for this end point | |||||||||||
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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.
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End point type |
Primary
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End point timeframe |
Baseline and End-of-Study
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| 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. |
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| No statistical analyses for this end point | |||||||||||
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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.
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End point type |
Primary
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End point timeframe |
Baseline and End-of-Study
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| 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. |
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| No statistical analyses for this end point | |||||||||||
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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.
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End point type |
Primary
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End point timeframe |
Baseline and End-of-Study
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| 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. |
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| No statistical analyses for this end point | |||||||||||
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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. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
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. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
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. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
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. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
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. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
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. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
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. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
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. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
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. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
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. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
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. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
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. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
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. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||
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. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||||
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. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
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. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
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. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
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. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
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.
|
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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. |
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|
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| No statistical analyses for this end point | |||||||||||||
|
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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. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
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. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
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. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
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. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
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Timeframe for reporting adverse events |
Screening to End-of-Study; maximum 50.3 weeks
|
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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]).
|
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
|
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|
Reporting groups
|
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Reporting group title |
Safety Population
|
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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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|
|||
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. | |||
