Description ofchanges in that part of the nervous sstem that is processing visual information over an extended perion of time in patients with relapsing remitting multiple sclerosis who take Tecfidera

• Register: EUCTR
• Last refreshed on: 30 October 2017
• Main ID: EUCTR2014-000395-26-DE
• Date of registration: 09/04/2014
• Prospective Registration: Yes
• Primary sponsor: Biogen GmbH
• Public title: Description ofchanges in that part of the nervous sstem that is processing visual information over an extended perion of time in patients with relapsing remitting multiple sclerosis who take Tecfidera
• Scientific title: 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 - VISION
• Date of first enrolment: 07/08/2015
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000395-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: EDSS, MSFC, SDMT and Sloan chart measurements Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Germany

Contacts

• Name: Medical Affairs Manager Neurology
• Affiliation: Biogen GmbH

• Name: Medical Affairs Manager Neurology
• Affiliation: Biogen GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent from patients capable of giving or withholding full informed consent must be obtained before any assessment is performed.
2. Male or female subjects aged 18-64 years.
3. Subjects with a) relapsing remitting MS (RRMS) defined by 2010 revised McDonald (Polman et al., 2011) criteria OR b) early MS (100 patients, reference cohort)
a) Patients with diagnosis of RRMS must satisfy the approved therapeutic indication for dimethyl fumarate (DMF) (as per local SmPC) and must have been clinically stable on DMF for at least 4 and up to 16 weeks prior to screening visit
b) Patients in the reference cohort must have had a single neurological episode within 60 months before screening.
They have to be without immunomodulatory treatment at screening.
They must not have a progressive form of MS.
Patients for the reference cohort may be evaluated also retrospectively at selected sites if they have given full informed consent.
The following data have to be recorded or available for these reference patients:
- Demography
- Neurological examination / EDSS
- OCT
- Visual acuity (BCVA)

4. Patients with Expanded Disability Status Scale (EDSS) score of 0-5.5 (including).
5. RNFLT at screening (for RRMS patients) must be at least 84µm and high contrast ETDRS visal acuity >0.5 in at least one eye (OCT has to be confirmed by Central Reading Center). For reference patients criteria have to be fulfilled at time of first documented OCT measurement.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 600
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Patients that are unwilling or unable to comply with study requirements, or are deemed unsuitable for study participation as determined by the Investigator.
2. Patients that have major comorbid conditions that preclude participation in the study, as determined by the Investigator.
3. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG test (urine dipstick).
4. Women of childbearing potential and not using appropriate contraception (per local DMF SmPC) as determined by the Investigator.
5. Patients with known hypersensitivity to the active ingredient in the DMF drug product or to any of the excipients listed in the local DMF SmPC (for the RRMS cohort).
6. Patients with a contraindication to DMF according to SmPC (for the RRMS cohort)
7. Patients with an onset of acute optic neuritis within the last 3 months.
8. Patients with an MS relapse within the last 30 days
9. Concomitant use of drugs that may directly affect retinal structure and function (e.g. chronic systemic corticosteroids).
10. Patients with any ophthalmologic reason for RNFL pathology other than MS, such as: optic neuropathy, active advanced glaucoma, injury of the optic nerve based on the ophthalmologist’s clinical judgment.
11. Patients with evidence of advanced, non-proliferative or proliferative diabetic retinopathy.
12. Patients with presence of retinal conditions associated with edema, subretinal fluid, cysts, etc.
13. Patients with history or presence of severe myopia (> - 6 dpt).
14. Patients who participate in another interventional study.
15. Patients who are institutionalized by court or official order


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Relapsing Remitting Multiple Sclerosis (RRMS)
MedDRA version: 18.0 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Tecfidera
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Dimethyl fumarate
CAS Number: 624-49-7
Other descriptive name: DIMETHYL FUMARATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 240-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 12, 24, 36 months

Primary end point(s): Parameters of interest

-Ganglion cell and inner plexiform layer (GCIPL) thickness as measured by OCT at Baseline, months 12, 24, and 36
-Retinal nerve fiber layer thickness (RNFLT) as measured by OCT at Baseline, months 12, 24, and 36
-Optic nerve head volume (ONH-V) as measured by OCT at Baseline, months 12, 24, and 36
-Visual acuity (ETDRS, Landolt and Sloan charts) at Baseline, months 12, 24, and 36
-Visual quality of life (NEI-VFQ-25) at Baseline, months 12, 24, and 36
-EDSS at Baseline and months 12, 24 and 36
-Annual relapse rate (ARR) over 36 months
-AEs and SAEs over 36 months
-Central visual field as measured by perimetry at Baseline, months 12, 24, and 36
-Inner nuclear layer (INL) thickness as measured by OCT at Screening, Baseline, months 12, 24, and 36
-QoL (PRIMuS) at Baseline, months 12, 24 and 36
-Disability Progression (MSFC) at Baseline, months 12, 24 and 36
-Cognition (SDMT) at Baseline, months 12, 24 and 36

Secondary Objective: Not applicable

Main Objective: Evaluation of changes of the visual sysetm in RRMS patients treated with dimethyl fumarate assessed by RNFL thickness measured by OCT over 36 months

Secondary Outcome(s)

Secondary end point(s): not applicable

Timepoint(s) of evaluation of this end point: not applicable

Secondary ID(s)

GER-BGT-13-10586

Source(s) of Monetary Support

Biogen GmbH