Trial Outcomes & Findings for Follow up Study of Patients on Fingolimod Who Were Enrolled in the Original Biobank Study (CFTY720DDE01) (NCT NCT02720107)

Results Overview

Aim of trial was to was to show reduction of CD4+ and CD8+ naïve T cells (CCR7+CD45RA+), central memory T cells (CCR7+CD45RA-), central memory Th17 cells (CD4+ CCR4+ and CCR6+), and an elevation of 2 types of effector memory T cells TEM (CCR7- CD45RA-) and TEMRA (CCR7- CD45RA+) in peripheral venous blood. Changes from baseline to month 48 in biomarkers were analyzed for all patients in the FAS.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

133 participants

Primary outcome timeframe

Baseline up to approximately 48 months

Results posted on

2019-02-08

Participant Flow

There were 133 patients enrolled in the study but only 130 received drug

Participant milestones

Participant milestones
Measure	Fingolimod Patients did not receive any protocol specified treatment during this follow-up study. Patients remained on their current treatment regime (fingolimod), as determined by their regular treating physician (i.e. 0.5 mg fingolimod daily, single-arm).
Overall Study STARTED	130
Overall Study COMPLETED	130
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Follow up Study of Patients on Fingolimod Who Were Enrolled in the Original Biobank Study (CFTY720DDE01)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fingolimod n=130 Participants Patients did not receive any protocol specified treatment during this follow-up study. Patients remained on their current treatment regime (fingolimod), as determined by their regular treating physician (i.e. 0.5 mg fingolimod daily, single-arm).
Age, Continuous	40.1 years STANDARD_DEVIATION 8.54 • n=5 Participants
Sex: Female, Male Female	83 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants
Multiple Sclerosis History at screening of CFTY720DDE01 (Core) Difference of first symptons and diagnosis	2.4 years STANDARD_DEVIATION 3.56 • n=5 Participants
Multiple Sclerosis History at screening of CFTY720DDE01 (Core) Difference of dagnosis and tx start in Core	8.6 years STANDARD_DEVIATION 6.23 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to approximately 48 months

Population: required baseline and month 48 visit measurement of the respective cell count

Aim of trial was to was to show reduction of CD4+ and CD8+ naïve T cells (CCR7+CD45RA+), central memory T cells (CCR7+CD45RA-), central memory Th17 cells (CD4+ CCR4+ and CCR6+), and an elevation of 2 types of effector memory T cells TEM (CCR7- CD45RA-) and TEMRA (CCR7- CD45RA+) in peripheral venous blood. Changes from baseline to month 48 in biomarkers were analyzed for all patients in the FAS.

Outcome measures

Outcome measures
Measure	Fingolimod n=130 Participants Patients did not receive any protocol specified treatment during this follow-up study. Patients remained on their current treatment regime (fingolimod), as determined by their regular treating physician (i.e. 0.5 mg fingolimod daily, single-arm).
Change in T Cells Status (Decrease or Increase) at Month 48 (FAS) CD4+ Naïve T cells	-23.7 percentage of parent population Standard Error 0.62
Change in T Cells Status (Decrease or Increase) at Month 48 (FAS) CD4+Central memory T cells	-1.2 percentage of parent population Standard Error 0.59
Change in T Cells Status (Decrease or Increase) at Month 48 (FAS) CD4+ Effector memory T cells	22.2 percentage of parent population Standard Error 2.37
Change in T Cells Status (Decrease or Increase) at Month 48 (FAS) CD8+ Naïve T cells	-37.2 percentage of parent population Standard Error 0.38
Change in T Cells Status (Decrease or Increase) at Month 48 (FAS) CD8+ Central memory T cells	-1.6 percentage of parent population Standard Error 0.07
Change in T Cells Status (Decrease or Increase) at Month 48 (FAS) CD8+ Effector memory T cells	-12.9 percentage of parent population Standard Error 1.59
Change in T Cells Status (Decrease or Increase) at Month 48 (FAS) TH17 central memory cells	-0.6 percentage of parent population Standard Error 0.03

SECONDARY outcome

Timeframe: Baseline up to approximately 48 months

EDSS is a scale for assessing neurologic impairment in MS. It is a two-part system including (1) a series of scores in each of eight functional systems, and (2) the EDSS steps (ranging from 0 (normal) to 10 (death due to MS). The definition of disability progression was based on increases in EDSS from baseline and depended on the EDSS baseline value: Disability progression was defined as a 1.5 increase in EDSS from baseline in subjects with a baseline EDSS score between 0.0 and 0.5, as a 1.0 increase in EDSS from baseline in subjects with a baseline EDSS score between 1.0 and 5.0 inclusive and 0.5 increase from baseline in subjects with EDSS score \> 5.0.

Outcome measures

Outcome measures
Measure	Fingolimod n=130 Participants Patients did not receive any protocol specified treatment during this follow-up study. Patients remained on their current treatment regime (fingolimod), as determined by their regular treating physician (i.e. 0.5 mg fingolimod daily, single-arm).
Percentage of Participants With Disability Progression as Measured by Expanded Disability Status Scale (EDSS) (FAS)	21.54 percentage of participants

SECONDARY outcome

Timeframe: Baseline, month 6 up to approximately 48 months

EDSS is a scale for assessing neurologic impairment in MS. It is a two-part system including (1) a series of scores in each of eight functional systems, and (2) the EDSS steps (ranging from 0 (normal) to 10 (death due to MS). The definition of disability progression was based on increases in EDSS from baseline and depended on the EDSS baseline value: Disability progression was defined as a 1.5 increase in EDSS from baseline in subjects with a baseline EDSS score between 0.0 and 0.5, as a 1.0 increase in EDSS from baseline in subjects with a baseline EDSS score between 1.0 and 5.0 inclusive and 0.5 increase from baseline in subjects with EDSS score \> 5.0.

Outcome measures

Outcome measures
Measure	Fingolimod n=130 Participants Patients did not receive any protocol specified treatment during this follow-up study. Patients remained on their current treatment regime (fingolimod), as determined by their regular treating physician (i.e. 0.5 mg fingolimod daily, single-arm).
Change From Baseline in Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at Month 6 and Month 48 (FAS) Baseline	2.7 scores on a scale Standard Deviation 1.17
Change From Baseline in Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at Month 6 and Month 48 (FAS) Month 6	2.6 scores on a scale Standard Deviation 1.38
Change From Baseline in Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at Month 6 and Month 48 (FAS) Month 48	2.7 scores on a scale Standard Deviation 1.52
Change From Baseline in Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at Month 6 and Month 48 (FAS) Change from baseline to month 6	-0.1 scores on a scale Standard Deviation 0.69
Change From Baseline in Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at Month 6 and Month 48 (FAS) Change from month 6 to month 48	0.2 scores on a scale Standard Deviation 1.18
Change From Baseline in Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at Month 6 and Month 48 (FAS) Change from baseline to month 48	0.0 scores on a scale Standard Deviation 1.19

SECONDARY outcome

Timeframe: Baseline up to approximately 48 months

Population: analysis required valid samples for baseline and month 48

Changes in immune status of B cells (CD19+, CD20+, CD69+), monocytes (CD14+) and NK cells (CD56+) were analyzed as a percentage of parent cell population (CD4+, CD8+ or total lymphocytes) by flow cytometry

Outcome measures

Outcome measures
Measure	Fingolimod n=130 Participants Patients did not receive any protocol specified treatment during this follow-up study. Patients remained on their current treatment regime (fingolimod), as determined by their regular treating physician (i.e. 0.5 mg fingolimod daily, single-arm).
Change in Immune Status of B Cells, Monocytes and Natural Killer Cells (NK) Cells (FAS) B cells	-7.2 percentage of parent population Standard Error 0.42
Change in Immune Status of B Cells, Monocytes and Natural Killer Cells (NK) Cells (FAS) Monocytes	42.3 percentage of parent population Standard Error 2.03
Change in Immune Status of B Cells, Monocytes and Natural Killer Cells (NK) Cells (FAS) Natural Killer cells	28.0 percentage of parent population Standard Error 2.09

Adverse Events

Fingolimod 0.5 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Fingolimod 0.5 mg n=130 participants at risk fingolimod 0.5 mg
Investigations Blood immunoglobulin M decreased	0.77% 1/130 • (Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.(approximately 48 months)

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

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