TOFIINGO: Disease Control and Safety in Patients With Relapsing Remitting Multiple Sclerosis (RRMS) Switching From Natalizumab to Fingolimod

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01499667
• Collaborator: (none)
• Enrollment: 142
• Locations: 44
• Arms: 3
• Duration (Months): 14
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study evaluated disease control during different lengths of treatment transition from natalizumab to fingolimod.

Condition or Disease	Intervention/Treatment	Phase
Relapsing Remitting Multiple Sclerosis (RRMS)	Drug: Fingolimod; Drug: Placebo	Phase 3

Detailed Description

Patient were screened, signed an informed consent at visit 1, at the 2nd visit, all patient received a baseline infusion of Natalizumub and subsequently randomized to one of 3 treatment arms. At the randomization visit, the Washout Phase started, and eligible patients were randomized 1:1:1 to one of three treatment groups:

• 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod,

• 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod, or

• 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod.

Study Design

• Study Type: Interventional
• Actual Enrollment: 142 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 32-week, Patient- and Rater-blinded, Randomized, Multi-center, Parallel-group Study to Evaluate Disease Control and Safety in Patients With Relapsing Remitting Multiple Sclerosis Transferred From Previous Treatment With Natalizumab to Fingolimod (FTY720)
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 8-week washout + Fingolimod (FTY720) 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	Drug: Fingolimod; Fingolimod 0.5 mg capsules for oral administration once daily
Experimental: 12-week washout + Fingolimod (FTY720) 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	Drug: Fingolimod; Fingolimod 0.5 mg capsules for oral administration once daily; Drug: Placebo; Matching placebo in capsules for oral administration once daily.
Experimental: 16-week washout + Fingolimod (FTY720) 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day	Drug: Fingolimod; Fingolimod 0.5 mg capsules for oral administration once daily; Drug: Placebo; Matching placebo in capsules for oral administration once daily.

Outcome Measures

Primary Outcome Measures

1. Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) Through 8 Weeks of Fingolimod Treatment [Number of active T2 lesions from last natalizumab dose through 8 weeks of fingolimod treatment]

   Active lesions were measured on brain MRI scans, performed at week 8, compared to the prior scan. The primary variable was analyzed by fitting a negative binomial regression model adjusted for washout group.

Secondary Outcome Measures

1. Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) up to the Initiation of Fingolimod Treatment [8, 12 and 16 weeks (number of active T2 lesions during the washout period only)]

   Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated from baseline to beginning of treatment.

2. Number of Active (New or Newly Enlarging) T2 Lesions During the First 8 Weeks of Fingolimod Treatment [Number of active T2 lesions during 8 wks of fingolimod treatment]

   Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated for first 8 weeks of fingolimod treatment.

3. Number of Active (New or Newly Enlarging) T2 Lesions During the 24 Weeks After the Last Natalizumab Infusion (Baseline) [Baseline up to 24 weeks]

   Lesions will be measured by MRIs and the number of active (new or newly enlarging) T2 lesions will be calculated for 24 weeks from baseline.

4. Change From Baseline in Expanded Disability Status Scale (EDSS) by Washout Group [Baseline to week 16 and week 32]

   Kurtzke's Expanded Disability Status Scale (EDSS) measures the changes in neurologic impairment, either chronic (progression over time), or acute (MS relapses). The EDSS steps range from 0 (normal) to 10 (death due to MS). Relapse severity is assessed based on severity of neurologic impairment as evaluated using the EDSS.

5. Cumulative Number of Gadolinium-enhancing T1 Lesions From the Last Natalizumab Infusion [8 weeks and 24 weeks]

   Gadolinium-enhancing lesions will be measured on post-contrast T1-weighted brain MRI scans

6. Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Washout Period [Baseline to maximum of 16 weeks]

   Adverse events were summarized by the number of patients having any adverse event overall.

7. Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Fingolimod Treatment [Baseline to maximum of 16 weeks]

   Adverse events were summarized by the number of patients having any adverse event overall.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Patients must:

• Have relapsing remitting multiple sclerosis

• Have been on treatment with natalizumab for at least 6 months prior to screening and discontinuation is an option.

Exclusion Criteria:

Patients with:

• History of chronic immune disease

• Crohn's disease

• Certain cancers

• Uncontrolled diabetes

• Certain eye disorders

• Negative for varicella-zoster virus IgG antibodies

• Certain hepatic conditions

• Low white blood cell count

• On certain immunosuppressive medications or heart medications

• Resting heart rate less than 45 bpm.

• Certain heart conditions or certain lung conditions

• Inability to undergo MRI scans

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Box Hill	Victoria	Australia	3128
2	Novartis Investigative Site	Heidelberg	Victoria	Australia	3084
3	Novartis Investigative Site	Vienna		Austria	1010
4	Novartis Investigative Site	Prague 5		Czech Republic	150 00
5	Novartis Investigative Site	Praha 2		Czech Republic	128 08
6	Novartis Investigative Site	Teplice		Czech Republic	415 29
7	Novartis Investigative Site	Helsinki		Finland	00100
8	Novartis Investigative Site	Ostfildern	Baden-Wuerttemberg	Germany	73760
9	Novartis Investigative Site	Bad Mergentheim		Germany	97980
10	Novartis Investigative Site	Berlin		Germany	10713
11	Novartis Investigative Site	Berlin		Germany	12163
12	Novartis Investigative Site	Bielefeld		Germany	33647
13	Novartis Investigative Site	Bochum		Germany	44791
14	Novartis Investigative Site	Celle		Germany	29223
15	Novartis Investigative Site	Erbach		Germany	64711
16	Novartis Investigative Site	Erfurt		Germany	99089
17	Novartis Investigative Site	Hamburg		Germany	22083
18	Novartis Investigative Site	Itzehoe		Germany	25524
19	Novartis Investigative Site	Kandel		Germany	76870
20	Novartis Investigative Site	Krefeld		Germany	47805
21	Novartis Investigative Site	Leipzig		Germany	04275
22	Novartis Investigative Site	Münster		Germany	48149
23	Novartis Investigative Site	Neuburg		Germany	86633
24	Novartis Investigative Site	Neuruppin		Germany	16816
25	Novartis Investigative Site	Rüdersdorf		Germany	15562
26	Novartis Investigative Site	Siegen		Germany	57076
27	Novartis Investigative Site	Ulm		Germany	89073
28	Novartis Investigative Site	Athens	GR	Greece	115 25
29	Novartis Investigative Site	Ioannina	GR	Greece	455 00
30	Novartis Investigative Site	Thessaloniki	GR	Greece	570 10
31	Novartis Investigative Site	Athens		Greece	GR 151 25
32	Novartis Investigative Site	Athens		Greece	GR-106 76
33	Novartis Investigative Site	Budapest		Hungary	1074
34	Novartis Investigative Site	Budapest		Hungary	1085
35	Novartis Investigative Site	Ashkelon		Israel	78278
36	Novartis Investigative Site	Jerusalem		Israel	91120
37	Novartis Investigative Site	Milano	MI	Italy	20132
38	Novartis Investigative Site	Cefalù	PA	Italy	90015
39	Novartis Investigative Site	Málaga	Andalucia	Spain	29010
40	Novartis Investigative Site	Sevilla	Andalucia	Spain	41009
41	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
42	Novartis Investigative Site	Barcelona		Spain	08025
43	Novartis Investigative Site	Madrid		Spain	28046
44	Novartis Investigative Site	Basel		Switzerland	4031

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01499667
• Other Study ID Numbers: CFTY720D2324; 2011-001442-15
• First Posted: Dec 26, 2011
• Last Update Posted: Aug 8, 2014
• Last Verified: Aug 1, 2014

• Keywords provided by Novartis Pharmaceuticals: Relapsing remitting multiple sclerosis; multiple sclerosis (MS); safety; tolerability; health outcomes; fingolimod; disease control; MRI
• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Fingolimod Hydrochloride

Study Results

Participant Flow

Recruitment Details	Of the 158 patients screened, 142 patients were randomized.
Pre-assignment Detail	142 Participants were randomized to 3 washout groups in a ratio of 1:1:1

Arm/Group Title	8-week Washout + Fingolimod (FTY720)	12-week Washout + Fingolimod (FTY720)	16-week Washout + Fingolimod (FTY720)
Arm/Group Description	8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Period Title: Overall Study
STARTED	50	42	50
Full Analysis Set (FAS)	49	42	50
Modified Full Analysis Set	41	29	39
COMPLETED	41	31	40
NOT COMPLETED	9	11	10

Baseline Characteristics

Arm/Group Title	8-week Washout + Fingolimod (FTY720)	12-week Washout + Fingolimod (FTY720)	16-week Washout + Fingolimod (FTY720)	Total
Arm/Group Description	8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod	Total of all reporting groups
Overall Participants	50	42	50	142
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	41.2 (10.102)	41.9 (7.445)	41.8 (8.552)	41.6 (8.780)
Sex: Female, Male (Count of Participants)
Female	39 78%	21 50%	32 64%	92 64.8%
Male	11 22%	21 50%	18 36%	50 35.2%

Outcome Measures

1. Primary Outcome

Title	Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) Through 8 Weeks of Fingolimod Treatment
Description	Active lesions were measured on brain MRI scans, performed at week 8, compared to the prior scan. The primary variable was analyzed by fitting a negative binomial regression model adjusted for washout group.
Time Frame	Number of active T2 lesions from last natalizumab dose through 8 weeks of fingolimod treatment

Outcome Measure Data

Analysis Population Description

The modified Full Analysis Set (mFAS) included all patients in the Full Analysis Set who completed 8 weeks of fingolimod treatment and provided an MRI scan at this time point. The analysis of primary variable was performed on the mFAS.

Arm/Group Title	8-week Washout + Fingolimod (FTY720)	12-week Washout + Fingolimod (FTY720)	16-week Washout + Fingolimod (FTY720)
Arm/Group Description	8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Measure Participants	41	29	39
Mean (Standard Deviation) [Count of Active T2 Lesions]	2.1 (7.24)	1.7 (3.78)	8.2 (16.81)

2. Secondary Outcome

Title	Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) up to the Initiation of Fingolimod Treatment
Description	Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated from baseline to beginning of treatment.
Time Frame	8, 12 and 16 weeks (number of active T2 lesions during the washout period only)

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) included all randomized patients who had at least one recorded dose of natalizumab at the Week 0 visit, analyzed according to the washout group assigned at randomization

Arm/Group Title	8-week Washout + Fingolimod (FTY720)	12-week Washout + Fingolimod (FTY720)	16-week Washout + Fingolimod (FTY720)
Arm/Group Description	8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Measure Participants	49	42	50
Mean (Standard Deviation) [Count of active T2 lesions]	0.4 (2.71)	2.1 (11.15)	3.6 (7.54)

3. Secondary Outcome

Title	Number of Active (New or Newly Enlarging) T2 Lesions During the First 8 Weeks of Fingolimod Treatment
Description	Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated for first 8 weeks of fingolimod treatment.
Time Frame	Number of active T2 lesions during 8 wks of fingolimod treatment

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) included all randomized patients who had at least one recorded dose of natalizumab at the Week 0 visit, analyzed according to the washout group assigned at randomization

Arm/Group Title	8-week Washout + Fingolimod (FTY720)	12-week Washout + Fingolimod (FTY720)	16-week Washout + Fingolimod (FTY720)
Arm/Group Description	8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Measure Participants	49	42	50
Mean (Standard Deviation) [Count of Active T2 Lesions]	1.5 (4.56)	2.1 (5.50)	4.2 (10.24)

4. Secondary Outcome

Title	Number of Active (New or Newly Enlarging) T2 Lesions During the 24 Weeks After the Last Natalizumab Infusion (Baseline)
Description	Lesions will be measured by MRIs and the number of active (new or newly enlarging) T2 lesions will be calculated for 24 weeks from baseline.
Time Frame	Baseline up to 24 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) included all randomized patients who had at least one recorded dose of natalizumab at the Week 0 visit, analyzed according to the washout group assigned at randomization

Arm/Group Title	8-week Washout + Fingolimod (FTY720)	12-week Washout + Fingolimod (FTY720)	16-week Washout + Fingolimod (FTY720)
Arm/Group Description	8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Measure Participants	49	42	50
Mean (Standard Deviation) [Count of Active T2 Lesions]	3.2 (10.07)	4.4 (16.01)	7.7 (16.28)

5. Secondary Outcome

Title	Change From Baseline in Expanded Disability Status Scale (EDSS) by Washout Group
Description	Kurtzke's Expanded Disability Status Scale (EDSS) measures the changes in neurologic impairment, either chronic (progression over time), or acute (MS relapses). The EDSS steps range from 0 (normal) to 10 (death due to MS). Relapse severity is assessed based on severity of neurologic impairment as evaluated using the EDSS.
Time Frame	Baseline to week 16 and week 32

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) included all randomized patients who had at least one recorded dose of natalizumab at the Week 0 visit, analyzed according to the washout group assigned at randomization.

Arm/Group Title	8-week Washout + Fingolimod (FTY720)	12-week Washout + Fingolimod (FTY720)	16-week Washout + Fingolimod (FTY720)
Arm/Group Description	8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Measure Participants	49	42	50
Week 16 (n=40, 33, 39)	0.11 (0.330)	-0.03 (0.529)	0.23 (0.706)
Week 32 (n= 40,30,39)	0.11 (0.625)	-0.13 (0.524)	0.08 (0.748)

6. Secondary Outcome

Title	Cumulative Number of Gadolinium-enhancing T1 Lesions From the Last Natalizumab Infusion
Description	Gadolinium-enhancing lesions will be measured on post-contrast T1-weighted brain MRI scans
Time Frame	8 weeks and 24 weeks

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) included all randomized patients who had at least one recorded dose of natalizumab at the Week 0 visit, analyzed according to the washout group assigned at randomization.

Arm/Group Title	8-week Washout + Fingolimod (FTY720)	12-week Washout + Fingolimod (FTY720)	16-week Washout + Fingolimod (FTY720)
Arm/Group Description	8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Measure Participants	49	42	50
Week 8 (n=1,1,0)	25.0 (0)	2.0 (0)	NA (NA)
Week 24 (n=10,12,21)	6.3 (9.45)	3.4 (4.54)	3.6 (4.49)

7. Secondary Outcome

Title	Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Washout Period
Description	Adverse events were summarized by the number of patients having any adverse event overall.
Time Frame	Baseline to maximum of 16 weeks

Outcome Measure Data

Analysis Population Description

The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod

Arm/Group Title	8-week Washout + Fingolimod (FTY720)	12-week Washout + Fingolimod (FTY720)	16-week Washout + Fingolimod (FTY720)
Arm/Group Description	8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Measure Participants	50	42	50
Any Adverse Events	13 26%	12 28.6%	25 50%
Serious Adverse Events	0 0%	0 0%	1 2%
Death	0 0%	0 0%	0 0%

8. Secondary Outcome

Title	Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Fingolimod Treatment
Description	Adverse events were summarized by the number of patients having any adverse event overall.
Time Frame	Baseline to maximum of 16 weeks

Outcome Measure Data

Analysis Population Description

The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod

Arm/Group Title	8-week Washout + Fingolimod (FTY720)	12-week Washout + Fingolimod (FTY720)	16-week Washout + Fingolimod (FTY720)
Arm/Group Description	8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day	12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day	16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Measure Participants	50	42	50
Any Adverse Events	35 70%	20 47.6%	28 56%
Serious Adverse Events	2 4%	5 11.9%	3 6%
Death	0 0%	0 0%	0 0%

Adverse Events

Adverse Event Reporting Description	Safety Set (SS): The Safety Set included all randomized patients, analyzed according to the washout group most closely corresponding to the day on which they first received fingolimod. Safety and tolerability analysis were performed on the SS unless otherwise specified.
Arm/Group Title	8-week Washout + Fingolimod (FTY720)		12-week Washout + Fingolimod (FTY720)		16-week Washout + Fingolimod (FTY720)
Arm/Group Description	8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day		12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day		16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
All Cause Mortality
	8-week Washout + Fingolimod (FTY720)		12-week Washout + Fingolimod (FTY720)		16-week Washout + Fingolimod (FTY720)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	8-week Washout + Fingolimod (FTY720)		12-week Washout + Fingolimod (FTY720)		16-week Washout + Fingolimod (FTY720)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/50 (4%)		5/42 (11.9%)		4/50 (8%)
Cardiac disorders
Bradycardia	0/50 (0%)		0/42 (0%)		1/50 (2%)
Hepatobiliary disorders
Cholecystitis acute	0/50 (0%)		1/42 (2.4%)		0/50 (0%)
Cholelithiasis	0/50 (0%)		1/42 (2.4%)		0/50 (0%)
Infections and infestations
Pharyngitis	0/50 (0%)		1/42 (2.4%)		0/50 (0%)
Pneumonia	1/50 (2%)		0/42 (0%)		0/50 (0%)
Injury, poisoning and procedural complications
Femur fracture	1/50 (2%)		0/42 (0%)		0/50 (0%)
Investigations
Electrocardiogram T wave inversion	0/50 (0%)		0/42 (0%)		1/50 (2%)
Heart rate decreased	0/50 (0%)		1/42 (2.4%)		0/50 (0%)
Nervous system disorders
Epilepsy	0/50 (0%)		1/42 (2.4%)		0/50 (0%)
Multiple sclerosis relapse	0/50 (0%)		0/42 (0%)		2/50 (4%)
Syncope	0/50 (0%)		1/42 (2.4%)		0/50 (0%)
Psychiatric disorders
Depression suicidal	0/50 (0%)		1/42 (2.4%)		0/50 (0%)
Major depression	0/50 (0%)		0/42 (0%)		1/50 (2%)
Mental disorder due to a general medical condition	0/50 (0%)		0/42 (0%)		1/50 (2%)
Personality change	0/50 (0%)		0/42 (0%)		1/50 (2%)
Other (Not Including Serious) Adverse Events
	8-week Washout + Fingolimod (FTY720)		12-week Washout + Fingolimod (FTY720)		16-week Washout + Fingolimod (FTY720)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/50 (34%)		7/42 (16.7%)		14/50 (28%)
Infections and infestations
Nasopharyngitis	7/50 (14%)		1/42 (2.4%)		2/50 (4%)
Oral herpes	1/50 (2%)		3/42 (7.1%)		1/50 (2%)
Sinusitis	2/50 (4%)		1/42 (2.4%)		3/50 (6%)
Urinary tract infection	3/50 (6%)		1/42 (2.4%)		0/50 (0%)
Musculoskeletal and connective tissue disorders
Myalgia	3/50 (6%)		0/42 (0%)		0/50 (0%)
Nervous system disorders
Dizziness	3/50 (6%)		1/42 (2.4%)		3/50 (6%)
Headache	5/50 (10%)		3/42 (7.1%)		10/50 (20%)
Psychiatric disorders
Depression	1/50 (2%)		1/42 (2.4%)		3/50 (6%)
Respiratory, thoracic and mediastinal disorders
Cough	3/50 (6%)		0/42 (0%)		1/50 (2%)
Oropharyngeal pain	4/50 (8%)		0/42 (0%)		0/50 (0%)

Limitations/Caveats

Study was terminated due to new data on nataluzimab washout prior to treatment with other disease modifying treatments. The power to detect statistically significant differences between the washout groups based on the (-)binomial is estimated 30-40%.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.