Clinical trial NCT01705236: A 3-year Multi-center Study to Describe Changes of OCT Parameters Under Treatment With Gilenya®
Official title: A 3-year Multi-center Study to Describe the Long Term Changes of Optical Coherence Tomography (OCT) Parameters in Patients Under Treatment With Gilenya®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Relapsing Remitting Multiple Sclerosis RRMS
Keywords: Multiple sclerosis (MS)
MS
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-10-12
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: This was a 3-year, prospective, multi-center, open-label study to describe the long term changes of optical coherence tomography (OCT) parameters in RRMS patients under treatment with Fingolimod. It was designed to longitudinally study the degeneration of retinal axons by measuring change in RNFL thickness by latest OCT-technology.


Eligibility criteria: Inclusion Criteria

Patients eligible for inclusion in this study have to fulfill all of the following criteria:

1. Written informed consent must be obtained before any assessment is performed.
2. Male or female subjects aged 18-65 years.
3. Subjects with relapsing remitting MS defined by 2010 revised McDonald criteria (see Appendix 4).
4. Patients with Expanded Disability Status Scale (EDSS) score of 0-6.0 inclusive (see Appendix 6).
5. Patients stable on immunomodulatory treatment with fingolimod for at least 1 month and at most 4 months prior to screening according to local label
6. Neurologically stable with no evidence of relapse within 30 days prior to inclusion date
7. Sufficient ability to read, write, communicate and understand

Exclusion Criteria

Patients fulfilling any of the following criteria are not eligible for inclusion in this study:

1. Patients who have been treated with:

   * systemic corticosteroids or immunoglobulins within 1 month prior to screening;
   * immunosuppressive medications such as azathioprine, cyclophosphamide, or methotrexate within 3 months prior to screening;
   * monoclonal antibodies (including natalizumab) within 3 months prior to screening;
   * mitoxantrone within 6 months prior to screening
   * cladribine at any time.
2. Patients with any medically unstable condition, as assessed by the primary treating physician at each site.
3. Patients with any of the following cardiovascular conditions :

   * history of myocardial infarction or with current unstable ischemic heart disease;
   * Heart failure (NYHA III-IV) or any severe cardiac disease as determined by the Investigator (see Appendix 5);
   * history or presence of a second-degree AV block, Type II or a third-degree AV block
   * patients receiving Class Ia (ajmaline, disopyramide, procainamide, quinidine) or III antiarrhythmic drugs (e.g., amiodarone, bretylium, sotalol, ibulitide, azimilide, dofelitide);
   * proven history of sick sinus syndrome;
   * uncontrolled hypertension
4. Patients with severe respiratory disease, pulmonary fibrosis, or chronic obstructive pulmonary disease (Class III-IV).
5. Patients with history of specific MRI findings (tumor, subdural haematoma, post-contusional changes, territorial stroke, neurodegenerative disorders, aneurysm/arteriovenous malformation, evidence of past macroscopic haemorrhage, or other relevant MRI findings that would interfere with evaluation)
6. Any severe disability or clinical impairment that can prevent the patient to meet all study requirements at the investigator's discretion
7. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin
8. Patients who have received an investigational drug (excluding fingolimod) or therapy within 90 days or 5 half-lives of screening, whichever is longer.
9. 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 (serum)
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. history or presence of severe myopia

    1. in patients who have not had refractive surgery, a refractive error of greater than 6.00 diopters
    2. pathologic fundus changes of high myopia, such as retinal pigmentary atrophy, besides peripapillary atrophy (atrophy involving the macula) or a staphyloma
    3. in patients that have had previous refractive surgery, an axial eye length of greater than 26 mm
12. Acute optic neuritis within the past 6 months before screening
13. Evidence of advanced, non-proliferative or proliferative diabetic retinopathy
14. Presence of retinal conditions associated with edema, subretinal fluid, cysts, etc.
15. Concomitant use of drugs that may directly affect retinal structure and function (e.g.

chronic systemic corticosteroids \[\>30 consecutive days; doses higher than Cushing threshold e.g. prednisone 7.5mg/d\], intraocular anti-angiogenic drugs \[ranibizumab, bevacizumab\], intraocular steroids etc.)

Primary outcomes:
measure: Change From Baseline to Month 36 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)
timeFrame: Baseline, month 36
Secondary outcomes:
measure: Change From Baseline to Month 12 and 24 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)
timeFrame: Baseline, month 12, month 24
measure: Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)
timeFrame: Baseline, month 12, month 24, month 36
measure: Change From Baseline to Month 12, 24 and 36 in Total Macular Volume (TMV)
timeFrame: 12, 24 and 36 months
measure: Change From Baseline to Month 12, 24 and 36 in Ganglion Cell Inner Plexiform (GCIP)
timeFrame: Baseline, month 12, month 24, month 36
measure: Number of Participants With Adverse Events
timeFrame: 36 months
Other outcomes:
Locations:
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Duesseldorf
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Rostock
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Zuerich
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: