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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00774670




Registration number
NCT00774670
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
Assessment method [1] 0 0
ARR is the average number of relapses in a year calculated by negative binomial regression as the sum of confirmed relapses of all patients in the group divided by the sum of the number of days on study of all patients in the group and multiplied by 365.25. A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (\<37.5C) or known infection. A relapse must be confirmed by the Independent Evaluating Physician (examining neurologist). ARR estimates were calculated from a negative binomial regression model adjusted for treatment, pooled center, number of relapses in the previous 2 years prior to enrollment, and Baseline expanded disability status scale (EDSS).
Timepoint [1] 0 0
24 months
Secondary outcome [1] 0 0
Aggregate Annualized Relapse Rate (ARR) Estimate up to End of Study
Assessment method [1] 0 0
ARR is the average number of relapses in a year calculated by negative binomial regression as the sum of confirmed relapses of all patients in the group divided by the sum of the number of days on study of all patients in the group and multiplied by 365.25. A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (\<37.5C) or known infection. A relapse must be confirmed by the Independent Evaluating Physician (examining neurologist). ARR estimates were calculated from a negative binomial regression model adjusted for treatment, pooled center, number of relapses in the previous 2 years prior to enrollment, and Baseline expanded disability status scale (EDSS).
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
Assessment method [2] 0 0
Brain volume was measured using magnetic resonance imaging (MRI). Change from Baseline in brain volume is expressed as a percentage of the Baseline 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
Assessment method [3] 0 0
Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of new or newly enlarged T2 lesions, by year.
Timepoint [3] 0 0
From Baseline until Month 48
Secondary outcome [4] 0 0
Number of Gadolinium-enhanced T1 Lesions
Assessment method [4] 0 0
Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the 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)
Assessment method [5] 0 0
Change from Baseline in lesion volume was measured by MRI for T2 lesions and for T1 hypointense lesions.
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
Assessment method [6] 0 0
Disability progression was defined using the following criteria: One point increase from baseline in patients with Baseline Expanded Disability Status Scale (EDSS) score from 0 to 5.0; or half a point increase from Baseline in patients with Baseline EDSS score of 5.5 or above. A 3-month confirmed disability progression was defined as a 3-month sustained increase from Baseline in EDSS score. The EDSS quantifies disability in multiple sclerosis in 8 functional systems; the score ranges from 0 (normal) to 10 (death due to MS). Progression curves were generated by the Kaplan-Meier method.
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
Assessment method [7] 0 0
Disability progression was defined using the following criteria: One point increase from baseline in patients with Baseline Expanded Disability Status Scale (EDSS) score from 0 to 5.0; or half a point increase from Baseline in patients with Baseline EDSS score of 5.5 or above. A 6-month confirmed disability progression was defined as a 6-month sustained increase from Baseline in EDSS score. The EDSS quantifies disability in multiple sclerosis in 8 functional systems; the score ranges from 0 (normal) to 10 (death due to MS). Progression curves were generated by the Kaplan-Meier method.
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
Assessment method [8] 0 0
Estimates of the percentage of participants relapse-free at 24 months were generated from Kaplan-Meier curves of the time to first relapse. A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (\<37.5C) or infection. A relapse was confirmed by an Independent Evaluating Physician.
Timepoint [8] 0 0
24 months
Secondary outcome [9] 0 0
Percentage of Participants Relapse-free up to End of Study
Assessment method [9] 0 0
Estimates of the percentage of participants relapse-free at end of study were generated from Kaplan-Meier curves of the time to first relapse. A relapse was defined as the appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (\<37.5C) or infection. A relapse was confirmed by an Independent Evaluating Physician.
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
Assessment method [10] 0 0
The Multiple Sclerosis Functional Composite (MSFC) is a multidimensional clinical outcome measure that includes quantitative tests of leg function/ambulation (Timed 25-Foot Walk), arm function (9-Hole Peg Test), and cognitive function (Paced Auditory Serial Addition Test). The overall MSFC z-score as an average of the three standardized scores derived using baseline data pooled over each treatment arm as reference population. Higher scores reflect better neurological function and a positive change from Baseline indicates improvement.
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
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Georgia
Country [9] 0 0
United States of America
State/province [9] 0 0
Illinois
Country [10] 0 0
United States of America
State/province [10] 0 0
Indiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Iowa
Country [12] 0 0
United States of America
State/province [12] 0 0
Kansas
Country [13] 0 0
United States of America
State/province [13] 0 0
Kentucky
Country [14] 0 0
United States of America
State/province [14] 0 0
Maryland
Country [15] 0 0
United States of America
State/province [15] 0 0
Massachusetts
Country [16] 0 0
United States of America
State/province [16] 0 0
Michigan
Country [17] 0 0
United States of America
State/province [17] 0 0
Missouri
Country [18] 0 0
United States of America
State/province [18] 0 0
Nevada
Country [19] 0 0
United States of America
State/province [19] 0 0
New Hampshire
Country [20] 0 0
United States of America
State/province [20] 0 0
New Jersey
Country [21] 0 0
United States of America
State/province [21] 0 0
New Mexico
Country [22] 0 0
United States of America
State/province [22] 0 0
New York
Country [23] 0 0
United States of America
State/province [23] 0 0
North Carolina
Country [24] 0 0
United States of America
State/province [24] 0 0
Ohio
Country [25] 0 0
United States of America
State/province [25] 0 0
Oklahoma
Country [26] 0 0
United States of America
State/province [26] 0 0
Oregon
Country [27] 0 0
United States of America
State/province [27] 0 0
Pennsylvania
Country [28] 0 0
United States of America
State/province [28] 0 0
South Carolina
Country [29] 0 0
United States of America
State/province [29] 0 0
Tennessee
Country [30] 0 0
United States of America
State/province [30] 0 0
Texas
Country [31] 0 0
United States of America
State/province [31] 0 0
Vermont
Country [32] 0 0
United States of America
State/province [32] 0 0
Virginia
Country [33] 0 0
United States of America
State/province [33] 0 0
Washington
Country [34] 0 0
United States of America
State/province [34] 0 0
West Virginia
Country [35] 0 0
United States of America
State/province [35] 0 0
Wisconsin
Country [36] 0 0
Austria
State/province [36] 0 0
Vienna
Country [37] 0 0
Canada
State/province [37] 0 0
Ontario
Country [38] 0 0
Canada
State/province [38] 0 0
Quebec
Country [39] 0 0
Poland
State/province [39] 0 0
Bialystok
Country [40] 0 0
Poland
State/province [40] 0 0
Warsaw
Country [41] 0 0
Poland
State/province [41] 0 0
Warszawa
Country [42] 0 0
Romania
State/province [42] 0 0
Bucharest
Country [43] 0 0
Romania
State/province [43] 0 0
Targu Mures
Country [44] 0 0
Turkey
State/province [44] 0 0
Istanbul
Country [45] 0 0
Turkey
State/province [45] 0 0
Izmir
Country [46] 0 0
Turkey
State/province [46] 0 0
Yenisehir/Izmir
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Bristol

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00774670