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Efficacy and Safety of Fingolimod in Patients With Relapsing-remitting Multiple Sclerosis (FREEDOMS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00289978
First received: February 9, 2006
Last updated: April 9, 2012
Last verified: April 2012
Results First Received: January 4, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Relapsing-remitting Multiple Sclerosis
Interventions: Drug: Fingolimod 1.25 mg
Drug: Fingolimod 0.5 mg
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Fingolimod 1.25 mg Patients self-administered fingolimod 1.25 mg capsules orally once daily.
Fingolimod 0.5 mg Patients self-administered fingolimod 0.5 mg capsules orally once daily.
Placebo Patients self-administered a fingolimod placebo capsule orally once daily.

Participant Flow:   Overall Study
    Fingolimod 1.25 mg   Fingolimod 0.5 mg   Placebo
STARTED   429   425   418 
COMPLETED   332 [1]   369 [2]   332 [3] 
NOT COMPLETED   97   56   86 
Withdrawal by Subject                31                17                28 
Adverse Event                22                13                18 
Lack of Efficacy                13                6                25 
Abnormal laboratory value(s)                20                9                1 
Lost to Follow-up                3                5                7 
Protocol Violation                5                5                4 
Abnormal test procedure result(s)                2                1                1 
Death                1                0                2 
[1] 296 completed on study drug, 35 completed off study drug.
[2] 345 completed on study drug, 24 completed off study drug.
[3] 303 completed on study drug, 29 completed off study drug.



  Baseline Characteristics
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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
Fingolimod 1.25 mg Patients self-administered fingolimod 1.25 mg capsules orally once daily.
Fingolimod 0.5 mg Patients self-administered fingolimod 0.5 mg capsules orally once daily.
Placebo Patients self-administered a fingolimod placebo capsule orally once daily.
Total Total of all reporting groups

Baseline Measures
   Fingolimod 1.25 mg   Fingolimod 0.5 mg   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 429   425   418   1272 
Age 
[Units: Years]
Mean (Standard Deviation)
 37.4  (8.91)   36.6  (8.77)   37.2  (8.60)   37.1  (8.76) 
Age, Customized 
[Units: Participants]
       
<18 years   1   0   0   1 
18 -30   107   120   97   324 
31-40   147   162   165   474 
41-55   174   143   156   473 
Gender 
[Units: Participants]
       
Female   295   296   298   889 
Male   134   129   120   383 
Duration of multiple sclerosis since first symptoms 
[Units: Years]
Mean (Standard Deviation)
 8.4  (6.86)   8.0  (6.60)   8.1  (6.35)   8.2  (6.60) 
Number of relapses in last 2 years 
[Units: Relapses]
Mean (Standard Deviation)
 1.5  (0.81)   1.5  (0.76)   1.4  (0.73)   1.5  (0.77) 
Expanded Disability Status Scale (EDSS) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 2.41  (1.36)   2.30  (1.29)   2.49  (1.29)   2.40  (1.32) 
[1] The EDSS is a scale for assessing disability in 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel & bladder, cerebral, other functions). Based on scores in these 8 functional systems, an overall score ranging from 0 (normal) to 10 (death due to MS) is assigned. Patients with EDSS scores of 0.0 to 4.5 are fully ambulatory; patients with EDSS scores of 5.0 to 9.5 have impaired ambulation. EDSS was assessed by an evaluating physician at each site.


  Outcome Measures
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1.  Primary:   Estimated Annualized Aggregate Relapse Rate (ARR)   [ Time Frame: Baseline to end of study (Month 24) ]

Measure Type Primary
Measure Title Estimated Annualized Aggregate Relapse Rate (ARR)
Measure Description The ARR is defined as the number of confirmed relapses in a year. A relapse is defined as the appearance of a new or worsening of a previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding relapse. The abnormality must be present for at least 24 hours and occur in the absence of fever or infection. The annualized ARR for each treatment group was the mean of the annualized ARRs for all patients in the group calculated as the total number of confirmed relapses divided by the total number of days on study, multiplied by 365.25.
Time Frame Baseline to end of study (Month 24)  
Safety Issue No  

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.
This analysis was conducted using the Intent-to-treat (ITT) population which includes all patients who were randomized and received at least one dose of study drug.

Reporting Groups
  Description
Fingolimod 1.25 mg Patients self-administered fingolimod 1.25 mg capsules orally once daily.
Fingolimod 0.5 mg Patients self-administered fingolimod 0.5 mg capsules orally once daily.
Placebo Patients self-administered a fingolimod placebo capsule orally once daily.

Measured Values
   Fingolimod 1.25 mg   Fingolimod 0.5 mg   Placebo 
Participants Analyzed 
[Units: Participants]
 429   425   418 
Estimated Annualized Aggregate Relapse Rate (ARR) 
[Units: Relapses per year]
Number (95% Confidence Interval)
 0.16 
 (0.13 to 0.19) 
 0.18 
 (0.15 to 0.22) 
 0.40 
 (0.34 to 0.47) 

No statistical analysis provided for Estimated Annualized Aggregate Relapse Rate (ARR)



2.  Secondary:   Percentage of Patients Free of Disability Progression at Month 24 Assessed With the Expanded Disability Status Scale (EDSS)   [ Time Frame: Baseline to end of study (Month 24) ]

Measure Type Secondary
Measure Title Percentage of Patients Free of Disability Progression at Month 24 Assessed With the Expanded Disability Status Scale (EDSS)
Measure Description EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) is calculated. Disability progression was determined by the following: One point increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point increase in patients with baseline EDSS score of 5.5 or above. A 3-month confirmed disability progression required onset EDSS, 3-month confirming EDSS, and all EDSS in between to meet the disability progression criteria. Percent of free of disability progression was calculated using the Kaplan Meier method.
Time Frame Baseline to end of study (Month 24)  
Safety Issue No  

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.
Intent-to-treat population (ITT): All patients who were randomized and received at least one dose of study medication.

Reporting Groups
  Description
Fingolimod 1.25 mg Patients self-administered fingolimod 1.25 mg capsules orally once daily.
Fingolimod 0.5 mg Patients self-administered fingolimod 0.5 mg capsules orally once daily.
Placebo Patients self-administered a fingolimod placebo capsule orally once daily.

Measured Values
   Fingolimod 1.25 mg   Fingolimod 0.5 mg   Placebo 
Participants Analyzed 
[Units: Participants]
 429   425   418 
Percentage of Patients Free of Disability Progression at Month 24 Assessed With the Expanded Disability Status Scale (EDSS) 
[Units: Percentage of participants]
Number (95% Confidence Interval)
 83.4 
 (79.7 to 87.1) 
 82.3 
 (78.6 to 86.1) 
 75.9 
 (71.7 to 80.2) 

No statistical analysis provided for Percentage of Patients Free of Disability Progression at Month 24 Assessed With the Expanded Disability Status Scale (EDSS)



3.  Secondary:   Number of New or Newly Enlarged T2 Lesions at Month 24 in Comparison With Baseline   [ Time Frame: Baseline to end of study (Month 24) ]

Measure Type Secondary
Measure Title Number of New or Newly Enlarged T2 Lesions at Month 24 in Comparison With Baseline
Measure Description The number of new or newly enlarged T2 lesions at Month 24 in comparison to baseline was assessed with T2-weighted magnetic resonance image (MRI) scans. A T2-weighted MRI scan utilizes particular values of the echo time (TE) and the repetition time (TR) parameters of image acquisition. Inflammation and tissue damage are seen as bright areas in T2 images and are often referred to as T2 lesions. T2-weighted MRI scans are a sensitive way to evaluate the brain for demyelinating diseases, such as multiple sclerosis.
Time Frame Baseline to end of study (Month 24)  
Safety Issue No  

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.
Intent-to-treat population (ITT): All patients who were randomized and received at least one dose of study medication.

Reporting Groups
  Description
Fingolimod 1.25 mg Patients self-administered fingolimod 1.25 mg capsules orally once daily.
Fingolimod 0.5 mg Patients self-administered fingolimod 0.5 mg capsules orally once daily.
Placebo Patients self-administered a fingolimod placebo capsule orally once daily.

Measured Values
   Fingolimod 1.25 mg   Fingolimod 0.5 mg   Placebo 
Participants Analyzed 
[Units: Participants]
 429   425   418 
Units Analyzed (Patients with non-missing values) 
[Units: Patients with non-missing values]
 337   370   339 
Number of New or Newly Enlarged T2 Lesions at Month 24 in Comparison With Baseline 
[Units: T2 lesions]
Mean (Standard Deviation)
 2.5  (5.52)   2.5  (7.19)   9.8  (13.17) 

No statistical analysis provided for Number of New or Newly Enlarged T2 Lesions at Month 24 in Comparison With Baseline




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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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