Efficacy and Safety of Fingolimod in Patients With Relapsing-remitting Multiple Sclerosis With Optional Extension Phase (TRANSFORMS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT00340834
First received: June 19, 2006
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

This study assessed the safety, tolerability, and efficacy of 2 doses of oral fingolimod versus interferon β-1a to reduce the frequency of relapses in patients with relapsing-remitting multiple sclerosis.


Condition Intervention Phase
Multiple Sclerosis
Drug: Fingolimod 1.25 mg
Drug: Fingolimod 0.5 mg
Drug: Interferon β-1a 30 µg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 12-month Double-blind, Randomized, Multicenter, Active-controlled, Parallel-group Study Comparing the Efficacy and Safety of 0.5 mg and 1.25 mg Fingolimod (FTY720) Administered Orally Once Daily Versus Interferon ß-1a (Avonex) Administered im Once Weekly in Patients With Relapsing-remitting Multiple Sclerosis With Optional Extension Phase

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Estimated Annualized Aggregate Relapse Rate (ARR) in the Core Phase of the Study [ Time Frame: Baseline to Month 12 ] [ Designated as safety issue: No ]
    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 calculated using negative binomial regression adjusted by treatment, country, number of relapses in the previous 2 years, and the baseline Expanded Disability Status Scale score.


Secondary Outcome Measures:
  • Number of New or Newly Enlarged T2 Lesions in Comparison With Baseline in the Core Phase of the Study [ Time Frame: Baseline to Month 12 ] [ Designated as safety issue: No ]
    The number of new or newly enlarged T2 lesions 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.

  • Percentage of Participants Free of 3-month Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at the End of the Core Phase of the Study [ Time Frame: Baseline to Month 12 ] [ Designated as safety issue: No ]
    The EDSS is a scale for assessing disability in 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel & bladder, cerebral, other functions). An overall score ranging from 0 (normal) to 10 (death due to MS) is calculated. Disability progression was determined by the EDSS score based on the following criteria: 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. Percent of patients free of disability progression was calculated using the Kaplan-Meier method.

  • Estimated Annualized Aggregate Relapse Rate (ARR) in the Core and Extension Phases of the Study [ Time Frame: Month 0 to end of study (up to approximately 4.5 years) ] [ Designated as safety issue: No ]
    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 calculated using negative binomial regression adjusted by treatment, country, number of relapses in the previous 2 years, and the baseline Expanded Disability Status Scale score.

  • Number of New or Newly Enlarged T2 Lesions in the Extension Phase of the Study [ Time Frame: Month 12 to end of study (up to approximately 3.5 years) ] [ Designated as safety issue: No ]
    The number of new or newly enlarged T2 lesions 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.

  • Percentage of Participants Free of 3-month and 6-month Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at the End of the Extension Phase of the Study [ Time Frame: Baseline to end of study (up to approximately 4.5 years) ] [ Designated as safety issue: No ]
    The EDSS is a scale for assessing disability in 8 functional systems (visual, brain stem, pyramidal, cerebellar, sensory, bowel & bladder, cerebral, other functions). An overall score ranging from 0 (normal) to 10 (death due to MS) is calculated. Disability progression was determined by the EDSS score based on the following criteria: 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. Percent of patients free of disability progression was calculated using the Kaplan-Meier method.


Enrollment: 1292
Study Start Date: May 2006
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fingolimod 1.25 mg Drug: Fingolimod 1.25 mg

Core: Patients self-administered fingolimod 1.25 mg capsules orally once daily. In addition, they self-administered an interferon β-1a placebo intramuscular (im) injection once weekly.

Extension: Patients self-administered fingolimod 1.25 mg capsules orally once daily until switched to 0.5 mg capsules upon study protocol amendment.

Other Name: FTY720
Experimental: Fingolimod 0.5 mg Drug: Fingolimod 0.5 mg

Core: Patients self-administered fingolimod 0.5 mg capsules orally once daily. In addition, they self-administered an interferon β-1a placebo intramuscular (im) injection once weekly.

Extension: Patients self-administered fingolimod 0.5 mg capsules orally once daily.

Other Name: FTY720
Active Comparator: Interferon β-1a 30 µg Drug: Interferon β-1a 30 µg

Core: Patients self-administered interferon β-1a 30 μg in an intramuscular (im) injection once weekly. In addition, they self-administered a fingolimod placebo capsule orally once daily.

Extension: Patients self-administered either fingolimod 1.25 mg or 0.5 mg capsules orally once daily until switched to 0.5 mg capsules upon study protocol amendment.


  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients between ages 18-55 with a diagnosis of multiple sclerosis (MS)
  • Patients with a relapsing-remitting disease course
  • Patients with Expanded Disability Status Scale (EDSS) score of 0-5.5

Exclusion Criteria:

  • Patients with other chronic disease of the immune system, malignancies, acute pulmonary disease, cardiac failure, etc
  • Pregnant or nursing women
  • Patients who cannot tolerate treatment with an interferon

Other protocol-defined inclusion/exclusion criteria applied to the study.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00340834

  Show 170 Study Locations
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmacuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00340834     History of Changes
Other Study ID Numbers: CFTY720D2302, CFTY720D2302E1
Study First Received: June 19, 2006
Results First Received: January 4, 2011
Last Updated: January 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
FTY720
Interferon
RRMS
Multiple Sclerosis
Efficacy

Additional relevant MeSH terms:
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Interferon beta 1a
Interferons
Interferon-beta
Fingolimod
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on September 16, 2014