This Was an Open-label, Single-arm Extension Study (CFTY720D2306E1) to a Double-blind, Randomized Multicenter, Placebo-controlled, Parallel-group Core Study (CFTY720D2306) in PPMS. (INFORMS)

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients were randomized equally to receive either fingolimod or placebo. Patients initially randomized to fingolimod 1.25 mg/day or matching placebo groups switched in a blinded manner to fingolimod 0.5 mg/day or continued on placebo after amendment in Nov. 2009. Patients were randomized to receive either fingolimod 0.5 mg/day or placebo..

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Prior to protocol amendment 147 patients received 1.25mg of FTY720; post protocol amendment 5 not all 147 patients switched to 0.5mg FTY720, only 121 switched and their data is presented under the 0.5mg dose.

Reporting Groups

	Description
FTY720 1.25 mg to 0.5 mg	Cohort 1: fingolimod 1.25 group consists of patients who were initially randomized to fingolimod 1.25 mg and switched to fingolimod 0.5 mg after amendment
FTY720 0.5 mg to 0.5 mg	Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
Placebo to -FTY 0.5 mg	Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization

Participant Flow for 2 periods

Period 1:   Core Study (36 Months)

	FTY720 1.25 mg to 0.5 mg	FTY720 0.5 mg to 0.5 mg	Placebo to -FTY 0.5 mg
STARTED	147	336	487
Safety Set (SAF)	0	336	487
Full Analysis Set (FAS)	0	336	487
Pharmacokinetic Analysis Set	102	249	0
Post Protocol Amendment 5 Switch	0	121 [1]	0
COMPLETED	79	220	317
NOT COMPLETED	68	116	170
Lack of Efficacy	11	23	64
Physician Decision	1	0	2
Death	2	1	2
Lost to Follow-up	1	3	3
Administrative	2	2	6
Abnormal Test Procedure Result	4	3	5
Protocol Violation	4	5	8
Abnormal Lab values	6	19	5
Adverse Event	25	28	29
Withdrawal by Subject	12	32	46

Period 2:   Extension Phase

	FTY720 1.25 mg to 0.5 mg	FTY720 0.5 mg to 0.5 mg	Placebo to -FTY 0.5 mg
STARTED	74	196	301
COMPLETED	0	0	0
NOT COMPLETED	74	196	301
Admin Problems: Terminated # patients	69	189	277
Abnormal test procedure	0	0	1
Abnormal lab values	0	0	1
Lost to Follow-up	0	1	4
Withdrawal by Subject	4	5	3
Adverse Event	1	1	15

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups

	Description
FTY720 1.25 mg to 0.5 mg	Cohort 1: fingolimod 1.25 group consists of patients who were initially randomized to fingolimod 1.25 mg and switched to fingolimod 0.5 mg after amendment
FTY720 0.5 mg to 0.5 mg	Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment)
Placebo	Cohort 1 and 2: Patients who started on placebo continued on placebo after re-randomization
Total	Total of all reporting groups

Baseline Measures

	FTY720 1.25 mg to 0.5 mg	FTY720 0.5 mg to 0.5 mg	Placebo	Total
Overall Participants Analyzed  [Units: Participants]	147	336	487	970
Age  [Units: Years] Mean (Standard Deviation)	47.8  (8.47)	48.5  (8.59)	48.5  (8.31)	48.5  (8.42)
Age, Customized  [Units: Particpants]
<=30	3	6	4	13
31 to 40	22	60	90	172
41 to 50	68	127	194	389
>50	54	143	199	396
Sex: Female, Male  [Units: Participants] Count of Participants
Female	71  48.3%	163  48.5%	235  48.3%	469  48.4%
Male	76  51.7%	173  51.5%	252  51.7%	501  51.6%

1.  Primary:

Kaplan-Meier Estimate of the Risk of 3-month Confirmed Disability Progression Based on Composite Endpoint   [ Time Frame: up to 36 months after the last patient was randomized ]

2.  Secondary:

Kaplan-Meier Estimate of the Risk of 3- Month Confirmed Disability Progression Based on Expanded Disability Status Scale (EDSS)   [ Time Frame: up to 36 months after the last patient was randomized ]

3.  Secondary:

Percent Change From Baseline in Brain Volume at Month 36   [ Time Frame: Baseline to month 36 ]

4.  Secondary:

Kaplan Meier Estimate -Percentage of Participants With 3- Month Confirmed Disability Progression Based on 9-HPT.   [ Time Frame: up to 36 months after the last patient was randomized ]

5.  Secondary:

Kaplan Meier Estimate -Percentage of Participants With 3- Month Confirmed Disability Progression Based on 25' TWT.   [ Time Frame: up to 36 months after the last patient was randomized ]

6.  Secondary:

Number of New/Enlarging T2 Lesions Per Year Measured From Baseline to Month 36   [ Time Frame: Baseline to 36 months ]

7.  Secondary:

Number of Gd-enhancing Lesions at Month 36   [ Time Frame: Baseline to 36 months ]

8.  Secondary:

Percent Change in Total T2 Lesion Volume From Baseline to Month 36   [ Time Frame: Baseline to month 36 ]

9.  Secondary:

Change From Baseline in the Patient Reported Indices in Multiple Sclerosis (PRIMUS-QoL Score)   [ Time Frame: Baseline, 36 months ]

10.  Secondary:

Change From Baseline in PRIMUS-Activities   [ Time Frame: Baseline, 36 months ]

11.  Secondary:

Change From Baseline in Unidimensional Fatigue Impact (U-FIS) Score   [ Time Frame: Baseline, 36 months ]

12.  Secondary:

Change From Baseline in European Quality of Life – 5 Dimensions (EQ-5D Score)   [ Time Frame: Baseline, 36 months ]

13.  Secondary:

Change From Baseline in Multiple Sclerosis Walking Scale (MSWS-12 Score)   [ Time Frame: Baseline, 36 months ]

14.  Secondary:

Blood Concentrations of Fingolimod and Fingolimod-phosphate   [ Time Frame: Month 3 up to 36 months ]

15.  Secondary:

Change in MSFC Z-score and Subscale Scores From Baseline to Month 36   [ Time Frame: Baseline to Month 36 ]

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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