Trial Outcomes & Findings for A 3-year Multi-center Study to Describe Changes of OCT Parameters Under Treatment With Gilenya® (NCT NCT01705236)
NCT ID: NCT01705236
Last Updated: 2020-03-02
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
87 participants
Primary outcome timeframe
Baseline, month 36
Results posted on
2020-03-02
Participant Flow
Subjects were screened at 10 study centers in Germany (9 centers) and Switzerland (1 center).
Subjects who passed the screening were enrolled in the trial.
Participant milestones
| Measure |
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.
|
|---|---|
|
Overall Study
STARTED
|
87
|
|
Overall Study
COMPLETED
|
60
|
|
Overall Study
NOT COMPLETED
|
27
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Administrative problems
|
2
|
|
Overall Study
Unsatisfactory therapeutic effect
|
3
|
|
Overall Study
Protocol Violation
|
3
|
|
Overall Study
Abnormal test procedure result(s)
|
4
|
|
Overall Study
Abnormal laboratory value(s)
|
4
|
|
Overall Study
Withdrawal by Subject
|
5
|
|
Overall Study
Adverse Event
|
5
|
Baseline Characteristics
A 3-year Multi-center Study to Describe Changes of OCT Parameters Under Treatment With Gilenya®
Baseline characteristics by cohort
| Measure |
Fingolimod - Longitudinal Assessment
n=87 Participants
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.
|
|---|---|
|
Age, Continuous
|
35.9 Years
STANDARD_DEVIATION 9.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
55 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
84 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, month 36Population: Full Analysis Set (FAS). The FAS consisted of all subjects treated with fingolimod who had at least one post-baseline efficacy assessment.
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).
Outcome measures
| Measure |
Fingolimod - Longitudinal Assessment
n=72 Participants
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.
|
|---|---|
|
Change From Baseline to Month 36 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)
|
-1.5 micrometer
Standard Deviation 2.7
|
SECONDARY outcome
Timeframe: Baseline, month 12, month 24Population: Full Analysis Set (FAS). The FAS consisted of all subjects treated with fingolimod who had at least one post-baseline efficacy assessment.
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).
Outcome measures
| Measure |
Fingolimod - Longitudinal Assessment
n=72 Participants
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.
|
|---|---|
|
Change From Baseline to Month 12 and 24 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)
Change from baseline to month 12
|
-0.8 micrometer
Standard Deviation 2.4
|
|
Change From Baseline to Month 12 and 24 in Average Retinal Nerve Fiber Layer Thickness (RNFLT)
Change from baseline to month 24
|
-1.1 micrometer
Standard Deviation 2.4
|
SECONDARY outcome
Timeframe: Baseline, month 12, month 24, month 36Population: Full Analysis Set (FAS). The FAS consisted of all subjects treated with fingolimod who had at least one post-baseline efficacy assessment.
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.
Outcome measures
| Measure |
Fingolimod - Longitudinal Assessment
n=72 Participants
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.
|
|---|---|
|
Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)
Nasal-superior RNFL thickness: month 12
|
0.5 micrometer
Standard Deviation 4.0
|
|
Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)
Nasal-superior RNFL thickness: month 24
|
-0.4 micrometer
Standard Deviation 3.4
|
|
Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)
Nasal-superior RNFL thickness: month 36
|
-0.7 micrometer
Standard Deviation 3.9
|
|
Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)
Nasal-inferior RNFL thickness: month 12
|
-1.2 micrometer
Standard Deviation 4.9
|
|
Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)
Nasal-inferior RNFL thickness: month 24
|
-1.6 micrometer
Standard Deviation 5.1
|
|
Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)
Nasal-inferior RNFL thickness: month 36
|
-2.1 micrometer
Standard Deviation 5.2
|
|
Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)
Temporal-inferior RNFL thickness: month 12
|
-1.2 micrometer
Standard Deviation 2.5
|
|
Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)
Temporal-inferior RNFL thickness: month 24
|
-1.6 micrometer
Standard Deviation 3.1
|
|
Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)
Temporal-inferior RNFL thickness: month 36
|
-2.3 micrometer
Standard Deviation 4.1
|
|
Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)
Temporal-superior RNFL thickness: month 12
|
-0.5 micrometer
Standard Deviation 3.9
|
|
Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)
Temporal-superior RNFL thickness: month 24
|
-0.4 micrometer
Standard Deviation 3.4
|
|
Change From Baseline to Month 12, 24 and 36 in Average Quadrant Retinal Nerve Fiber Layer Thickness (RNFLT)
Temporal-superior RNFL thickness: month 36
|
-1.1 micrometer
Standard Deviation 4.1
|
SECONDARY outcome
Timeframe: 12, 24 and 36 monthsPopulation: Full Analysis Set (FAS). The FAS consisted of all subjects treated with fingolimod who had at least one post-baseline efficacy assessment.
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).
Outcome measures
| Measure |
Fingolimod - Longitudinal Assessment
n=72 Participants
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.
|
|---|---|
|
Change From Baseline to Month 12, 24 and 36 in Total Macular Volume (TMV)
Change from baseline to month 12
|
-0.03 Cubic millimeter
Standard Deviation 0.08
|
|
Change From Baseline to Month 12, 24 and 36 in Total Macular Volume (TMV)
Change from baseline to month 24
|
-0.04 Cubic millimeter
Standard Deviation 0.08
|
|
Change From Baseline to Month 12, 24 and 36 in Total Macular Volume (TMV)
Change from baseline to month 36
|
-0.06 Cubic millimeter
Standard Deviation 0.10
|
SECONDARY outcome
Timeframe: Baseline, month 12, month 24, month 36Population: Full Analysis Set (FAS). The FAS consisted of all subjects treated with fingolimod who had at least one post-baseline efficacy assessment.
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.
Outcome measures
| Measure |
Fingolimod - Longitudinal Assessment
n=72 Participants
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.
|
|---|---|
|
Change From Baseline to Month 12, 24 and 36 in Ganglion Cell Inner Plexiform (GCIP)
Change from baseline to month 36
|
-0.46 micrometer
Standard Deviation 3.01
|
|
Change From Baseline to Month 12, 24 and 36 in Ganglion Cell Inner Plexiform (GCIP)
Change from baseline to month 12
|
-0.49 micrometer
Standard Deviation 2.39
|
|
Change From Baseline to Month 12, 24 and 36 in Ganglion Cell Inner Plexiform (GCIP)
Change from baseline to month 24
|
-0.42 micrometer
Standard Deviation 2.74
|
SECONDARY outcome
Timeframe: 36 monthsPopulation: Safety Population (SAF). The SAF consisted of all subjects treated with fingolimod for whom safety information had been collected.
Number of participants with adverse events and specifically macular edema.
Outcome measures
| Measure |
Fingolimod - Longitudinal Assessment
n=87 Participants
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.
|
|---|---|
|
Number of Participants With Adverse Events
No. of subjects with any AE
|
80 Participants
|
|
Number of Participants With Adverse Events
No. of subjects with macular edema
|
0 Participants
|
Adverse Events
Fingolimod - Longitudinal Assessment
Serious events: 11 serious events
Other events: 68 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Fingolimod - Longitudinal Assessment
n=87 participants at risk
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.
|
|---|---|
|
Cardiac disorders
AORTIC VALVE INCOMPETENCE
|
1.1%
1/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Infections and infestations
ERYSIPELAS
|
1.1%
1/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Infections and infestations
GASTROENTERITIS VIRAL
|
1.1%
1/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Infections and infestations
OPHTHALMIC HERPES ZOSTER
|
1.1%
1/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Infections and infestations
WOUND INFECTION
|
1.1%
1/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Injury, poisoning and procedural complications
LOWER LIMB FRACTURE
|
1.1%
1/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Injury, poisoning and procedural complications
RADIUS FRACTURE
|
1.1%
1/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Injury, poisoning and procedural complications
SUTURE RELATED COMPLICATION
|
1.1%
1/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Musculoskeletal and connective tissue disorders
INTERVERTEBRAL DISC PROTRUSION
|
1.1%
1/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CERVIX CARCINOMA STAGE 0
|
1.1%
1/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NASAL NEOPLASM
|
1.1%
1/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
UTERINE LEIOMYOMA
|
1.1%
1/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Nervous system disorders
MULTIPLE SCLEROSIS RELAPSE
|
2.3%
2/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Nervous system disorders
NEURALGIC AMYOTROPHY
|
1.1%
1/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Nervous system disorders
UHTHOFF'S PHENOMENON
|
1.1%
1/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Reproductive system and breast disorders
CERVICAL DYSPLASIA
|
1.1%
1/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
Other adverse events
| Measure |
Fingolimod - Longitudinal Assessment
n=87 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
LYMPHOPENIA
|
10.3%
9/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Gastrointestinal disorders
DIARRHOEA
|
6.9%
6/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Infections and infestations
BRONCHITIS
|
6.9%
6/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Infections and infestations
CONJUNCTIVITIS
|
5.7%
5/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Infections and infestations
NASOPHARYNGITIS
|
47.1%
41/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Infections and infestations
SINUSITIS
|
6.9%
6/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
8.0%
7/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Infections and infestations
URINARY TRACT INFECTION
|
8.0%
7/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Metabolism and nutrition disorders
VITAMIN D DEFICIENCY
|
9.2%
8/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
5.7%
5/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
8.0%
7/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Nervous system disorders
DIZZINESS
|
5.7%
5/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Nervous system disorders
HEADACHE
|
11.5%
10/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Nervous system disorders
MULTIPLE SCLEROSIS RELAPSE
|
24.1%
21/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Nervous system disorders
PARAESTHESIA
|
5.7%
5/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Psychiatric disorders
DEPRESSION
|
5.7%
5/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
6.9%
6/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
5.7%
5/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
|
Vascular disorders
HYPERTENSION
|
13.8%
12/87 • Adverse events were collected from first dose of study treatment until end of study treatment up to maximum duration of 36 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER