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

This study has been terminated.
(Based on recent publications, determination of natalizumub washout period was no longer relevant.)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01499667
First received: August 18, 2011
Last updated: August 6, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
Relapsing Remitting Multiple Sclerosis (RRMS)
Drug: Fingolimod
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated from baseline to beginning of treatment.

  • 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 ] [ Designated as safety issue: No ]
    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 (New or Newly Enlarging) T2 Lesions During the 24 Weeks After the Last Natalizumab Infusion (Baseline) [ Time Frame: Baseline up to 24 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Expanded Disability Status Scale (EDSS) by Washout Group [ Time Frame: Baseline to week 16 and week 32 ] [ Designated as safety issue: No ]
    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.

  • Cumulative Number of Gadolinium-enhancing T1 Lesions From the Last Natalizumab Infusion [ Time Frame: 8 weeks and 24 weeks ] [ Designated as safety issue: No ]
    Gadolinium-enhancing lesions will be measured on post-contrast T1-weighted brain MRI scans

  • Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Washout Period [ Time Frame: Baseline to maximum of 16 weeks ] [ Designated as safety issue: Yes ]
    Adverse events were summarized by the number of patients having any adverse event overall.

  • Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Fingolimod Treatment [ Time Frame: Baseline to maximum of 16 weeks ] [ Designated as safety issue: Yes ]
    Adverse events were summarized by the number of patients having any adverse event overall.


Enrollment: 142
Study Start Date: September 2011
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  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: NCT01499667

  Show 44 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01499667     History of Changes
Other Study ID Numbers: CFTY720D2324, 2011-001442-15
Study First Received: August 18, 2011
Results First Received: November 25, 2013
Last Updated: August 6, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
United Kingdom: Medicines and Healthcare Products Regulatory Agency
European Union: European Medicines Agency

Keywords provided by Novartis:
Relapsing remitting multiple sclerosis
multiple sclerosis (MS)
safety
tolerability
health outcomes
fingolimod
disease control
MRI

Additional relevant MeSH terms:
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes
Fingolimod
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014