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)

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Primary Progressive Multiple Sclerosis
Interventions:	Drug: FTY720; Drug: Placebo

  Participant Flow

  Hide Participant Flow

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

[1]	post protocol amendment 121 patients switch to 0.5 mg dose from 125mg dose

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

  Baseline Characteristics

  Hide Baseline Characteristics

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.
No text entered.

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%

  Outcome Measures

  Show All Outcome Measures

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 ]

  Show Outcome Measure 1

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 ]

  Show Outcome Measure 2

3. Secondary:

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

  Show Outcome Measure 3

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 ]

  Show Outcome Measure 4

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 ]

  Show Outcome Measure 5

6. Secondary:

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

  Show Outcome Measure 6

7. Secondary:

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

  Show Outcome Measure 7

8. Secondary:

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

  Show Outcome Measure 8

9. Secondary:

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

  Show Outcome Measure 9

10. Secondary:

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

  Show Outcome Measure 10

11. Secondary:

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

  Show Outcome Measure 11

12. Secondary:

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

  Show Outcome Measure 12

13. Secondary:

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

  Show Outcome Measure 13

14. Secondary:

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

  Show Outcome Measure 14

15. Secondary:

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

  Show Outcome Measure 15

  Serious Adverse Events

  Show Serious Adverse Events

  Other Adverse Events

  Show Other Adverse Events

  Limitations and Caveats

  Hide Limitations and Caveats

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
No text entered.

  More Information

  Hide More Information

Certain Agreements:  

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is: The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo. The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.; Restriction Description: 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

Results Point of Contact:  

Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300
e-mail: trialandresults.registries@novartis.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Miller DH, Lublin FD, Sormani MP, Kappos L, Yaldizli Ö, Freedman MS, Cree BAC, Weiner HL, Lubetzki C, Hartung HP, Montalban X, Uitdehaag BMJ, MacManus DG, Yousry TA, Gandini Wheeler-Kingshott CAM, Li B, Putzki N, Merschhemke M, Häring DA, Wolinsky JS. Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study. Ann Clin Transl Neurol. 2018 Jan 30;5(3):346-356. doi: 10.1002/acn3.534. eCollection 2018 Mar.

Lublin F, Miller DH, Freedman MS, Cree BAC, Wolinsky JS, Weiner H, Lubetzki C, Hartung HP, Montalban X, Uitdehaag BMJ, Merschhemke M, Li B, Putzki N, Liu FC, Häring DA, Kappos L; INFORMS study investigators. Oral fingolimod in primary progressive multiple sclerosis (INFORMS): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2016 Mar 12;387(10023):1075-1084. doi: 10.1016/S0140-6736(15)01314-8. Epub 2016 Jan 28. Erratum in: Lancet. 2017 Jan 21;389(10066):254.

Hartung HP, Aktas O. Bleak prospects for primary progressive multiple sclerosis therapy: downs and downs, but a glimmer of hope. Ann Neurol. 2009 Oct;66(4):429-32. doi: 10.1002/ana.21880.

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT00731692 History of Changes
Obsolete Identifiers:	NCT01779934
Other Study ID Numbers:	CFTY720D2306; 2007-002627-32 ( EudraCT Number )
First Submitted:	August 7, 2008
First Posted:	August 11, 2008
Results First Submitted:	December 16, 2015
Results First Posted:	June 14, 2017
Last Update Posted:	June 14, 2017