Disease Control and Safety in Patients With Relapsing Remitting Multiple Sclerosis (RRMS) Switching From Natalizumab to Fingolimod (TOFIINGO)

August 6, 2014 updated by: Novartis Pharmaceuticals

A 32-week, Patient- and Rater-blinded, Randomized, Multi-center, Parallel-group Study to Evaluate Disease Control and Safety in Patients With Relapsing Remitting Multiple Sclerosis Transferred From Previous Treatment With Natalizumab to Fingolimod (FTY720)

This study evaluated disease control during different lengths of treatment transition from natalizumab to fingolimod.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Patient were screened, signed an informed consent at visit 1, at the 2nd visit, all patient received a baseline infusion of Natalizumub and subsequently randomized to one of 3 treatment arms. At the randomization visit, the Washout Phase started, and eligible patients were randomized 1:1:1 to one of three treatment groups:

  • 8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod,
  • 12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod, or
  • 16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod.

Study Type

Interventional

Enrollment (Actual)

142

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Box Hill, Victoria, Australia, 3128
        • Novartis Investigative Site
      • Heidelberg, Victoria, Australia, 3084
        • Novartis Investigative Site
  • Austria
      • Vienna, Austria, 1010
        • Novartis Investigative Site
  • Czech Republic
      • Prague 5, Czech Republic, 150 00
        • Novartis Investigative Site
      • Praha 2, Czech Republic, 128 08
        • Novartis Investigative Site
      • Teplice, Czech Republic, 415 29
        • Novartis Investigative Site
  • Finland
      • Helsinki, Finland, 00100
        • Novartis Investigative Site
  • Germany
      • Bad Mergentheim, Germany, 97980
        • Novartis Investigative Site
      • Berlin, Germany, 10713
        • Novartis Investigative Site
      • Berlin, Germany, 12163
        • Novartis Investigative Site
      • Bielefeld, Germany, 33647
        • Novartis Investigative Site
      • Bochum, Germany, 44791
        • Novartis Investigative Site
      • Celle, Germany, 29223
        • Novartis Investigative Site
      • Erbach, Germany, 64711
        • Novartis Investigative Site
      • Erfurt, Germany, 99089
        • Novartis Investigative Site
      • Hamburg, Germany, 22083
        • Novartis Investigative Site
      • Itzehoe, Germany, 25524
        • Novartis Investigative Site
      • Kandel, Germany, 76870
        • Novartis Investigative Site
      • Krefeld, Germany, 47805
        • Novartis Investigative Site
      • Leipzig, Germany, 04275
        • Novartis Investigative Site
      • Münster, Germany, 48149
        • Novartis Investigative Site
      • Neuburg, Germany, 86633
        • Novartis Investigative Site
      • Neuruppin, Germany, 16816
        • Novartis Investigative Site
      • Rüdersdorf, Germany, 15562
        • Novartis Investigative Site
      • Siegen, Germany, 57076
        • Novartis Investigative Site
      • Ulm, Germany, 89073
        • Novartis Investigative Site
    • Baden-Wuerttemberg
      • Ostfildern, Baden-Wuerttemberg, Germany, 73760
        • Novartis Investigative Site
  • Greece
      • Athens, Greece, GR-106 76
        • Novartis Investigative Site
      • Athens, Greece, GR 151 25
        • Novartis Investigative Site
    • GR
      • Athens, GR, Greece, 115 25
        • Novartis Investigative Site
      • Ioannina, GR, Greece, 455 00
        • Novartis Investigative Site
      • Thessaloniki, GR, Greece, 570 10
        • Novartis Investigative Site
  • Hungary
      • Budapest, Hungary, 1085
        • Novartis Investigative Site
      • Budapest, Hungary, 1074
        • Novartis Investigative Site
  • Israel
      • Ashkelon, Israel, 78278
        • Novartis Investigative Site
      • Jerusalem, Israel, 91120
        • Novartis Investigative Site
  • Italy
    • MI
      • Milano, MI, Italy, 20132
        • Novartis Investigative Site
    • PA
      • Cefalù, PA, Italy, 90015
        • Novartis Investigative Site
  • Spain
      • Barcelona, Spain, 08025
        • Novartis Investigative Site
      • Madrid, Spain, 28046
        • Novartis Investigative Site
    • Andalucia
      • Málaga, Andalucia, Spain, 29010
        • Novartis Investigative Site
      • Sevilla, Andalucia, Spain, 41009
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
  • Switzerland
      • Basel, Switzerland, 4031
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Patients must:

  • Have relapsing remitting multiple sclerosis
  • Have been on treatment with natalizumab for at least 6 months prior to screening and discontinuation is an option.

Exclusion Criteria:

Patients with:

  • History of chronic immune disease
  • Crohn's disease
  • Certain cancers
  • Uncontrolled diabetes
  • Certain eye disorders
  • Negative for varicella-zoster virus IgG antibodies
  • Certain hepatic conditions
  • Low white blood cell count
  • On certain immunosuppressive medications or heart medications
  • Resting heart rate less than 45 bpm.
  • Certain heart conditions or certain lung conditions
  • Inability to undergo MRI scans

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 8-week washout + Fingolimod (FTY720)
8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day
Drug: Fingolimod
Fingolimod 0.5 mg capsules for oral administration once daily
EXPERIMENTAL: 12-week washout + Fingolimod (FTY720)
12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day
Drug: Fingolimod
Fingolimod 0.5 mg capsules for oral administration once daily
Drug: Placebo
Matching placebo in capsules for oral administration once daily.
EXPERIMENTAL: 16-week washout + Fingolimod (FTY720)
16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Drug: Fingolimod
Fingolimod 0.5 mg capsules for oral administration once daily
Drug: Placebo
Matching placebo in capsules for oral administration once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) Through 8 Weeks of Fingolimod Treatment
Time Frame: Number of active T2 lesions from last natalizumab dose through 8 weeks of fingolimod treatment
Active lesions were measured on brain MRI scans, performed at week 8, compared to the prior scan. The primary variable was analyzed by fitting a negative binomial regression model adjusted for washout group.
Number of active T2 lesions from last natalizumab dose through 8 weeks of fingolimod treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) up to the Initiation of Fingolimod Treatment
Time Frame: 8, 12 and 16 weeks (number of active T2 lesions during the washout period only)
Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated from baseline to beginning of treatment.
8, 12 and 16 weeks (number of active T2 lesions during the washout period only)
Number of Active (New or Newly Enlarging) T2 Lesions During the First 8 Weeks of Fingolimod Treatment
Time Frame: Number of active T2 lesions during 8 wks of fingolimod treatment
Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated for first 8 weeks of fingolimod treatment.
Number of active T2 lesions during 8 wks of fingolimod treatment
Number of Active (New or Newly Enlarging) T2 Lesions During the 24 Weeks After the Last Natalizumab Infusion (Baseline)
Time Frame: Baseline up to 24 weeks
Lesions will be measured by MRIs and the number of active (new or newly enlarging) T2 lesions will be calculated for 24 weeks from baseline.
Baseline up to 24 weeks
Change From Baseline in Expanded Disability Status Scale (EDSS) by Washout Group
Time Frame: Baseline to week 16 and week 32
Kurtzke's Expanded Disability Status Scale (EDSS) measures the changes in neurologic impairment, either chronic (progression over time), or acute (MS relapses). The EDSS steps range from 0 (normal) to 10 (death due to MS). Relapse severity is assessed based on severity of neurologic impairment as evaluated using the EDSS.
Baseline to week 16 and week 32
Cumulative Number of Gadolinium-enhancing T1 Lesions From the Last Natalizumab Infusion
Time Frame: 8 weeks and 24 weeks
Gadolinium-enhancing lesions will be measured on post-contrast T1-weighted brain MRI scans
8 weeks and 24 weeks
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Washout Period
Time Frame: Baseline to maximum of 16 weeks
Adverse events were summarized by the number of patients having any adverse event overall.
Baseline to maximum of 16 weeks
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Fingolimod Treatment
Time Frame: Baseline to maximum of 16 weeks
Adverse events were summarized by the number of patients having any adverse event overall.
Baseline to maximum of 16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2011

Primary Completion (ACTUAL)

November 1, 2012

Study Completion (ACTUAL)

November 1, 2012

Study Registration Dates

First Submitted

August 18, 2011

First Submitted That Met QC Criteria

December 22, 2011

First Posted (ESTIMATE)

December 26, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

August 8, 2014

Last Update Submitted That Met QC Criteria

August 6, 2014

Last Verified

August 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CFTY720D2324
  • 2011-001442-15 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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