A 3-year Multi-center Study to Describe Changes of OCT Parameters Under Treatment With Gilenya®

A 3-year Multi-center Study to Describe the Long Term Changes of Optical Coherence Tomography (OCT) Parameters in Patients Under Treatment With Gilenya®

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01705236

Acronym

PASSOS

Enrollment

Registered

2012-10-12

Start date

2012-08-20

Completion date

2019-02-18

Last updated

2020-03-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Relapsing Remitting Multiple Sclerosis RRMS

Keywords

Multiple sclerosis (MS), MS

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.

Interventions

DRUGFingolimod

All subjects received an oral dose of 0.5 mg fingolimod (FTY720) per capsule (hard gelatin capsules) once daily according to local label for the treatment of their MS.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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.)

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline to Month 36 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)	Baseline, month 36	The primary endpoint was the change, i.e. the absolute difference, in average RNFL thickness from baseline to month 36 (or last values in case of missing data) in the Full Analysis Set (FAS). Average RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT).

Secondary

Measure	Time frame	Description
Change From Baseline to Month 12 and 24 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)	Baseline, month 12, month 24	Change from baseline in average RNFL thickness to months 12 and 24 (or last values in case of missing data) in the Full Analysis Set (FAS). Average RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT).
Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)	Baseline, month 12, month 24, month 36	Change from baseline in average quadrant RNFL thickness to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS). Average quadrant RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT). Quadrant RNFL thickness were: Nasal-inferior; nasal-superior; temporal-inferior; temporal-superior.
Change From Baseline to Month 12, 24 and 36 in Total Macular Volume (TMV)	12, 24 and 36 months	Change from baseline in TMV to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS).
Change From Baseline to Month 12, 24 and 36 in Ganglion Cell Inner Plexiform (GCIP)	Baseline, month 12, month 24, month 36	Change from baseline in GCIP to months 12, 24 and 36 (or last values in case of missing data) in the Full Analysis Set (FAS). The change in Ganglion cell layer thickness (GCLT) had been defined as secondary endpoint in the protocol, but OCT measured the GCIP instead. This was done because both layers were not clearly separable by OCT. GCIP was calculated as mean of the inner sectors (nasal, superior, temporal, and inferior) and declared as usual parameter instead. This change was introduced prior to data base lock, but the derivation of GCIP was corrected after data base lock.
Number of Participants With Adverse Events	36 months	Number of participants with adverse events and specifically macular edema.

Countries

Germany, Switzerland

Participant flow

Recruitment details

Subjects were screened at 10 study centers in Germany (9 centers) and Switzerland (1 center).

Pre-assignment details

Subjects who passed the screening were enrolled in the trial.

Participants by arm

Arm	Count
Fingolimod - Longitudinal Assessment No study drug was provided. Fingolimod was to be prescribed according to local label. The decision to prescribe fingolimod was to be made independent of this study.	87
Total	87

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Abnormal laboratory value(s)	4
Overall Study	Abnormal test procedure result(s)	4
Overall Study	Administrative problems	2
Overall Study	Adverse Event	5
Overall Study	Lost to Follow-up	1
Overall Study	Protocol Violation	3
Overall Study	Unsatisfactory therapeutic effect	3
Overall Study	Withdrawal by Subject	5

Baseline characteristics

Characteristic	Fingolimod - Longitudinal Assessment
Age, Continuous	35.9 Years STANDARD_DEVIATION 9.5
Race/Ethnicity, Customized Caucasian	84 Participants
Race/Ethnicity, Customized Other	3 Participants
Sex: Female, Male Female	55 Participants
Sex: Female, Male Male	32 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 87
other Total, other adverse events	68 / 87
serious Total, serious adverse events	11 / 87

Outcome results

Primary

Change From Baseline to Month 36 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)

The primary endpoint was the change, i.e. the absolute difference, in average RNFL thickness from baseline to month 36 (or last values in case of missing data) in the Full Analysis Set (FAS). Average RNFL thickness was the average of valid measurements of the right and left eye and assessed by optical coherence tomography (OCT).

Time frame: Baseline, month 36