Trial Outcomes & Findings for Efficacy of Fingolimod in de Novo Patients Versus Fingolimod in Patients Previously Treated With a First Line Disease Modifying Therapy (NCT NCT01498887)

NCT ID: NCT01498887

Last Updated: 2019-01-25

Results Overview

ARR = 365 days \* number of relapses / total days taking the study medication.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

347 participants

Primary outcome timeframe

12 months

Results posted on

2019-01-25

Participant Flow

This was an open-label, non-randomized, parallel group study.

Participant milestones

Participant milestones
Measure	Naive or de Novo Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.	Previously Treated With First-line DMTs Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.
Overall Study STARTED	200	147
Overall Study Safety Set	200	147
Overall Study Intent-to-treat	185	135
Overall Study COMPLETED	184	136
Overall Study NOT COMPLETED	16	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Naive or de Novo Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.	Previously Treated With First-line DMTs Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.
Overall Study Administrative problems	1	0
Overall Study Lost to Follow-up	1	1
Overall Study Withdrawal by Subject	1	0
Overall Study Protocol Violation	1	3
Overall Study Lack of Efficacy	5	3
Overall Study Abnormal result from test procedure	1	1
Overall Study Abnormal laboratory value	2	2
Overall Study Adverse Event	4	1

Baseline Characteristics

Efficacy of Fingolimod in de Novo Patients Versus Fingolimod in Patients Previously Treated With a First Line Disease Modifying Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Naive or de Novo Participants n=185 Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.	Previously Treated With First-line DMTs Participants n=135 Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.	Total n=320 Participants Total of all reporting groups
Age, Continuous	33.1 Years STANDARD_DEVIATION 8.08 • n=5 Participants	34.0 Years STANDARD_DEVIATION 7.44 • n=7 Participants	33.5 Years STANDARD_DEVIATION 7.81 • n=5 Participants
Sex: Female, Male Female	137 Participants n=5 Participants	88 Participants n=7 Participants	225 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	47 Participants n=7 Participants	95 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: The ITT population was analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded.

ARR = 365 days \* number of relapses / total days taking the study medication.

Outcome measures

Outcome measures
Measure	Naive or de Novo Participants n=185 Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.	Previously Treated With First-line DMTs Participants n=135 Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.
Annual Relapse Rate (ARR)	0.290 Relapses per year Standard Deviation 0.7399	0.354 Relapses per year Standard Deviation 0.8547

SECONDARY outcome

Timeframe: first day of treatment to the first day of a new neurological symptom or worsening of an existing one, up to 12 months

Time to first relapse was defined as the time from the first day of treatment to the first day of a new neurological symptom or worsening of an existing one.

Outcome measures

Outcome measures
Measure	Naive or de Novo Participants n=185 Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.	Previously Treated With First-line DMTs Participants n=135 Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.
Time to First Relapse	NA months Since less than half of the ITT population had a relapse, the median time since fingolimod treatment initiation to the first relapse was not reached.	NA months Since less than half of the ITT population had a relapse, the median time since fingolimod treatment initiation to the first relapse was not reached.

SECONDARY outcome

Timeframe: baseline, 12 months

Population: Participants from the ITT population with both baseline and 12 month values were analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded.

The EDSS is an ordinal clinical rating scale ranging from a total score of 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Naive or de Novo Participants n=182 Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.	Previously Treated With First-line DMTs Participants n=130 Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.
Change From Baseline in Expanded Disability Status Scale (EDSS) Score	0.000 score on a scale Standard Deviation 0.8040	-0.077 score on a scale Standard Deviation 0.7911

SECONDARY outcome

Timeframe: baseline, 12 months

Cerebral volume was assessed by magnetic resonance imaging (MRI). A negative change from baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Naive or de Novo Participants n=92 Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.	Previously Treated With First-line DMTs Participants n=43 Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.
Change From Baseline in Cerebral Volume	-0.595 Percent change Interval -0.759 to -0.431	-0.387 Percent change Interval -0.583 to -0.191

SECONDARY outcome

Timeframe: 12 months

Population: Only participants from the ITT population with severity values were analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded.

The investigator classified a relapse as moderate-severe if oral or intravenous (IV) treatment (according to the local clinical practice) with steroids and/or hospitalization was needed. If neither oral nor IV treatment with steroids nor hospitalization was needed, the relapse was considered as mild.

Outcome measures

Outcome measures
Measure	Naive or de Novo Participants n=47 Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.	Previously Treated With First-line DMTs Participants n=39 Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.
Percentage of Participants With Mild, Moderate or Severe Relapse Mild	42.55 Percentage of participants	38.46 Percentage of participants
Percentage of Participants With Mild, Moderate or Severe Relapse Moderate	57.45 Percentage of participants	56.41 Percentage of participants
Percentage of Participants With Mild, Moderate or Severe Relapse Severe	0.00 Percentage of participants	5.13 Percentage of participants

SECONDARY outcome

Timeframe: 12 months

Relapse-free participants were defined as participants who experienced no new neurological symptom or worsening of an existing one (relapses) during the 12-month treatment period with 0.5 mg fingolimod.

Outcome measures

Outcome measures
Measure	Naive or de Novo Participants n=185 Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.	Previously Treated With First-line DMTs Participants n=135 Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.
Percentage of Relapse-free Participants	71.89 Percent	66.67 Percent

SECONDARY outcome

Timeframe: 12 months

Population: Participants from the ITT population with 12 month T2 lesion numbers were analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded.

The mean number of new or enlarged T2 active lesions was assessed by MRI.

Outcome measures

Outcome measures
Measure	Naive or de Novo Participants n=163 Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.	Previously Treated With First-line DMTs Participants n=106 Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.
Mean Number of T2 Active Lesions	2.0 T2 lesions Standard Deviation 3.36	1.6 T2 lesions Standard Deviation 2.72

Adverse Events

Naive or de Novo Participants

Serious events: 11 serious events

Other events: 143 other events

Deaths: 0 deaths

Previously Treated With First-line DMTs Participants

Serious events: 4 serious events

Other events: 114 other events

Deaths: 0 deaths

All Participants

Serious events: 15 serious events

Other events: 257 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Naive or de Novo Participants n=200 participants at risk Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.	Previously Treated With First-line DMTs Participants n=147 participants at risk Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.	All Participants n=347 participants at risk
Cardiac disorders Atrioventricular block	0.50% 1/200 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.00% 0/147 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.29% 1/347 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.
Cardiac disorders Atrioventricular block second degree	0.50% 1/200 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.00% 0/147 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.29% 1/347 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.
Cardiac disorders Bradycardia	0.00% 0/200 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.68% 1/147 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.29% 1/347 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.
Cardiac disorders Sinus bradycardia	1.0% 2/200 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.00% 0/147 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.58% 2/347 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.
Hepatobiliary disorders Cholelithiasis	1.0% 2/200 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.00% 0/147 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.58% 2/347 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.
Hepatobiliary disorders Hepatitis acute	0.50% 1/200 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.00% 0/147 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.29% 1/347 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.
Immune system disorders Drug hypersensitivity	0.00% 0/200 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.68% 1/147 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.29% 1/347 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.
Infections and infestations Lower respiratory tract infection	0.00% 0/200 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.68% 1/147 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.29% 1/347 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma	0.50% 1/200 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.00% 0/147 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.29% 1/347 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.
Nervous system disorders Brain oedema	0.50% 1/200 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.00% 0/147 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.29% 1/347 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.
Nervous system disorders Epilepsy	0.50% 1/200 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.00% 0/147 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.29% 1/347 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.
Nervous system disorders Multiple sclerosis relapse	1.0% 2/200 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.68% 1/147 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.86% 3/347 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.
Nervous system disorders Partial seizures	0.50% 1/200 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.00% 0/147 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.29% 1/347 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.
Reproductive system and breast disorders Ovarian cyst	0.50% 1/200 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.00% 0/147 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.	0.29% 1/347 • Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit, approximately 4 years.

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER