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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00355134




Registration number
NCT00355134
Ethics application status
Date submitted
19/07/2006
Date registered
21/07/2006
Date last updated
7/08/2012

Titles & IDs
Public title
Efficacy and Safety of Fingolimod (FTY720) in Patients With Relapsing-remitting Multiple Sclerosis
Scientific title
24-month Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study Comparing the Efficacy and Safety of 0.5 mg and 1.25 mg Fingolimod (FTY720) Administered Orally Once Daily Versus Placebo in Patients With Relapsing-remitting Multiple Sclerosis With Optional Extension Phase
Secondary ID [1] 0 0
CFTY720D2309
Universal Trial Number (UTN)
Trial acronym
FREEDOMS II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Fingolimod
Treatment: Drugs - Placebo

Experimental: Fingolimod 1.25 mg - Participants received 1.25 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 1.25 mg fingolimod orally once a day.

Note: Upon implementation of a protocol amendment all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day.

Experimental: Fingolimod 0.5 mg - Participants received 0.5 mg fingolimod orally once a day for up to 24 months during the core phase. In the Extension phase participants continued to receive 0.5 mg fingolimod orally once a day.

Experimental: Placebo - Participants received placebo capsules orally once a day for up to 24 months during the core phase. In the Extension phase participants received either 1.25 or 0.5 mg fingolimod orally once a day.

Note: Upon implementation of a protocol amendment all patients taking 1.25 mg fingolimod were switched to 0.5 mg fingolimod orally once a day. Upon implementation of a protocol amendment, all patients taking placebo were switched to 0.5 mg fingolimod orally once a day.


Treatment: Drugs: Fingolimod
Fingolimod capsules for oral administration

Treatment: Drugs: Placebo
Matching placebo capsules for oral administration.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Aggregate Annualized Relapse Rate (ARR) Estimate up to Month 24
Timepoint [1] 0 0
24 months
Secondary outcome [1] 0 0
Aggregate Annualized Relapse Rate (ARR) Estimate up to End of Study
Timepoint [1] 0 0
From Baseline until end of study (up to approximately 54 months).
Secondary outcome [2] 0 0
Percent Change From Baseline in Brain Volume
Timepoint [2] 0 0
Baseline, Month 24 and end of study (up to approximately 54 months)
Secondary outcome [3] 0 0
Number of New or Newly Enlarged T2 Lesions
Timepoint [3] 0 0
From Baseline until Month 48
Secondary outcome [4] 0 0
Number of Gadolinium-enhanced T1 Lesions
Timepoint [4] 0 0
Month 24 and end of study (up to approximately 54 months)
Secondary outcome [5] 0 0
Change From Baseline in Lesion Volume at Month 24 (Core Phase)
Timepoint [5] 0 0
Baseline and Month 24
Secondary outcome [6] 0 0
Percentage of Participants Free of 3-month Confirmed Disability Progression at Month 24 and End of Study
Timepoint [6] 0 0
24 months and end of study (up to approximately 54 months)
Secondary outcome [7] 0 0
Percentage of Participants Free of 6-month Confirmed Disability Progression at Month 24 and End of Study
Timepoint [7] 0 0
24 months and end of study (up to approximately 54 months)
Secondary outcome [8] 0 0
Percentage of Participants Relapse-free up to Month 24
Timepoint [8] 0 0
24 months
Secondary outcome [9] 0 0
Percentage of Participants Relapse-free up to End of Study
Timepoint [9] 0 0
From Baseline until the end of study (up to approximately 54 months)
Secondary outcome [10] 0 0
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Z-score
Timepoint [10] 0 0
Baseline, Month 24 and end of study (up to approximately 54 months)

Eligibility
Key inclusion criteria
* Male and female patients between ages 18-55 with a diagnosis of multiple sclerosis
* Patients with a relapsing-remitting disease course
* Patients with expanded disability status scale (EDSS) score of 0-5.5
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients with other chronic disease of the immune system, malignancies, acute pulmonary disease, cardiac failure, etc.
* Pregnant or nursing women

For inclusion in the extension phase patients should complete the 24 month core study with or without 24 months on study drug. If a patient discontinued study drug during the core study due to an adverse event, serious adverse event, laboratory abnormality etc. they would be excluded from the Extension Phase.

Other protocol-defined inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2011
Sample size
Target
Accrual to date
Final
1083
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Novartis Investigative Site - North Gosford
Recruitment postcode(s) [1] 0 0
- North Gosford
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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Arizona
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California
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Colorado
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Connecticut
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District of Columbia
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Florida
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Georgia
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Illinois
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Indiana
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Iowa
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Kansas
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Kentucky
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Maryland
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Massachusetts
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Michigan
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Missouri
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Nevada
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New Hampshire
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New Jersey
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New Mexico
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New York
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Vermont
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Virginia
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Washington
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West Virginia
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Wisconsin
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Austria
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Vienna
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Canada
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Ontario
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Canada
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Quebec
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Poland
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Bialystok
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Warsaw
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Poland
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Warszawa
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Romania
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Bucharest
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Romania
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Targu Mures
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Turkey
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Istanbul
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Turkey
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Izmir
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Turkey
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Yenisehir/Izmir
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United Kingdom
State/province [47] 0 0
Bristol

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study assessed the safety, tolerability and efficacy of two doses of oral fingolimod compared to placebo on efficacy parameters in patients with relapsing-remitting multiple sclerosis (RRMS).
Trial website
https://clinicaltrials.gov/study/NCT00355134
Trial related presentations / publications
Wang L, Tan H, Yu J, ZhangBao J, Huang W, Chang X, Zhou L, Lu C, Xiao Y, Lu J, Zhao C, Wang M, Wu X, Wu M, Dong Q, Ngew KY, Quan C. Baseline retinal nerve fiber layer thickness as a predictor of multiple sclerosis progression: New insights from the FREEDOMS II study. Eur J Neurol. 2023 Feb;30(2):443-452. doi: 10.1111/ene.15612. Epub 2022 Nov 15.
Fox RJ, Chan A, Zhang A, Xiao J, Levison D, Lewin JB, Edwards MR, Marantz JL. Comparative effectiveness using a matching-adjusted indirect comparison between delayed-release dimethyl fumarate and fingolimod for the treatment of multiple sclerosis. Curr Med Res Opin. 2017 Feb;33(2):175-183. doi: 10.1080/03007995.2016.1248380. Epub 2016 Nov 10.
Derfuss T, Bergvall NK, Sfikas N, Tomic DL. Efficacy of fingolimod in patients with highly active relapsing-remitting multiple sclerosis. Curr Med Res Opin. 2015;31(9):1687-91. doi: 10.1185/03007995.2015.1067191. Epub 2015 Aug 20.
Chinea Martinez AR, Correale J, Coyle PK, Meng X, Tenenbaum N. Efficacy and safety of fingolimod in Hispanic patients with multiple sclerosis: pooled clinical trial analyses. Adv Ther. 2014 Oct;31(10):1072-81. doi: 10.1007/s12325-014-0154-4. Epub 2014 Sep 23.
Calabresi PA, Radue EW, Goodin D, Jeffery D, Rammohan KW, Reder AT, Vollmer T, Agius MA, Kappos L, Stites T, Li B, Cappiello L, von Rosenstiel P, Lublin FD. Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2014 Jun;13(6):545-56. doi: 10.1016/S1474-4422(14)70049-3. Epub 2014 Mar 28. Erratum In: Lancet Neurol. 2013 Jun;13(6):536.
Winges KM, Werner JS, Harvey DJ, Cello KE, Durbin MK, Balcer LJ, Calabresi PA, Keltner JL. Baseline retinal nerve fiber layer thickness and macular volume quantified by OCT in the North American phase 3 fingolimod trial for relapsing-remitting multiple sclerosis. J Neuroophthalmol. 2013 Dec;33(4):322-9. doi: 10.1097/WNO.0b013e31829c51f7.
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00355134