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

Primary Purpose

Relapsing Remitting Multiple Sclerosis (RRMS)

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Fingolimod
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsing Remitting Multiple Sclerosis (RRMS) focused on measuring Relapsing remitting multiple sclerosis, multiple sclerosis (MS), safety, tolerability, health outcomes, fingolimod, disease control, MRI

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

8-week washout + Fingolimod (FTY720)

12-week washout + Fingolimod (FTY720)

16-week washout + Fingolimod (FTY720)

Arm Description

8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day

12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day

16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day

Outcomes

Primary Outcome Measures

Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) 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.

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
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
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)
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
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
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
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
Adverse events were summarized by the number of patients having any adverse event overall.

Full Information

First Posted
August 18, 2011
Last Updated
August 6, 2014
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01499667
Brief Title
Disease Control and Safety in Patients With Relapsing Remitting Multiple Sclerosis (RRMS) Switching From Natalizumab to Fingolimod
Acronym
TOFIINGO
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)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2014
Overall Recruitment Status
Terminated
Why Stopped
Based on recent publications, determination of natalizumub washout period was no longer relevant.
Study Start Date
September 2011 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsing Remitting Multiple Sclerosis (RRMS)
Keywords
Relapsing remitting multiple sclerosis, multiple sclerosis (MS), safety, tolerability, health outcomes, fingolimod, disease control, MRI

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
142 (Actual)

8. Arms, Groups, and Interventions

Arm Title
8-week washout + Fingolimod (FTY720)
Arm Type
Experimental
Arm Description
8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day
Arm Title
12-week washout + Fingolimod (FTY720)
Arm Type
Experimental
Arm Description
12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day
Arm Title
16-week washout + Fingolimod (FTY720)
Arm Type
Experimental
Arm Description
16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day
Intervention Type
Drug
Intervention Name(s)
Fingolimod
Intervention Description
Fingolimod 0.5 mg capsules for oral administration once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo in capsules for oral administration once daily.
Primary Outcome Measure Information:
Title
Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) Through 8 Weeks of Fingolimod Treatment
Description
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.
Time Frame
Number of active T2 lesions from last natalizumab dose through 8 weeks of fingolimod treatment
Secondary Outcome Measure Information:
Title
Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) up to the Initiation of Fingolimod Treatment
Description
Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated from baseline to beginning of treatment.
Time Frame
8, 12 and 16 weeks (number of active T2 lesions during the washout period only)
Title
Number of Active (New or Newly Enlarging) T2 Lesions During the First 8 Weeks of Fingolimod Treatment
Description
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.
Time Frame
Number of active T2 lesions during 8 wks of fingolimod treatment
Title
Number of Active (New or Newly Enlarging) T2 Lesions During the 24 Weeks After the Last Natalizumab Infusion (Baseline)
Description
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.
Time Frame
Baseline up to 24 weeks
Title
Change From Baseline in Expanded Disability Status Scale (EDSS) by Washout Group
Description
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.
Time Frame
Baseline to week 16 and week 32
Title
Cumulative Number of Gadolinium-enhancing T1 Lesions From the Last Natalizumab Infusion
Description
Gadolinium-enhancing lesions will be measured on post-contrast T1-weighted brain MRI scans
Time Frame
8 weeks and 24 weeks
Title
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Washout Period
Description
Adverse events were summarized by the number of patients having any adverse event overall.
Time Frame
Baseline to maximum of 16 weeks
Title
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Fingolimod Treatment
Description
Adverse events were summarized by the number of patients having any adverse event overall.
Time Frame
Baseline to maximum of 16 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Box Hill
State/Province
Victoria
ZIP/Postal Code
3128
Country
Australia
Facility Name
Novartis Investigative Site
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Novartis Investigative Site
City
Vienna
ZIP/Postal Code
1010
Country
Austria
Facility Name
Novartis Investigative Site
City
Prague 5
ZIP/Postal Code
150 00
Country
Czech Republic
Facility Name
Novartis Investigative Site
City
Praha 2
ZIP/Postal Code
128 08
Country
Czech Republic
Facility Name
Novartis Investigative Site
City
Teplice
ZIP/Postal Code
415 29
Country
Czech Republic
Facility Name
Novartis Investigative Site
City
Helsinki
ZIP/Postal Code
00100
Country
Finland
Facility Name
Novartis Investigative Site
City
Ostfildern
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
73760
Country
Germany
Facility Name
Novartis Investigative Site
City
Bad Mergentheim
ZIP/Postal Code
97980
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
10713
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
12163
Country
Germany
Facility Name
Novartis Investigative Site
City
Bielefeld
ZIP/Postal Code
33647
Country
Germany
Facility Name
Novartis Investigative Site
City
Bochum
ZIP/Postal Code
44791
Country
Germany
Facility Name
Novartis Investigative Site
City
Celle
ZIP/Postal Code
29223
Country
Germany
Facility Name
Novartis Investigative Site
City
Erbach
ZIP/Postal Code
64711
Country
Germany
Facility Name
Novartis Investigative Site
City
Erfurt
ZIP/Postal Code
99089
Country
Germany
Facility Name
Novartis Investigative Site
City
Hamburg
ZIP/Postal Code
22083
Country
Germany
Facility Name
Novartis Investigative Site
City
Itzehoe
ZIP/Postal Code
25524
Country
Germany
Facility Name
Novartis Investigative Site
City
Kandel
ZIP/Postal Code
76870
Country
Germany
Facility Name
Novartis Investigative Site
City
Krefeld
ZIP/Postal Code
47805
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04275
Country
Germany
Facility Name
Novartis Investigative Site
City
Münster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Novartis Investigative Site
City
Neuburg
ZIP/Postal Code
86633
Country
Germany
Facility Name
Novartis Investigative Site
City
Neuruppin
ZIP/Postal Code
16816
Country
Germany
Facility Name
Novartis Investigative Site
City
Rüdersdorf
ZIP/Postal Code
15562
Country
Germany
Facility Name
Novartis Investigative Site
City
Siegen
ZIP/Postal Code
57076
Country
Germany
Facility Name
Novartis Investigative Site
City
Ulm
ZIP/Postal Code
89073
Country
Germany
Facility Name
Novartis Investigative Site
City
Athens
State/Province
GR
ZIP/Postal Code
115 25
Country
Greece
Facility Name
Novartis Investigative Site
City
Ioannina
State/Province
GR
ZIP/Postal Code
455 00
Country
Greece
Facility Name
Novartis Investigative Site
City
Thessaloniki
State/Province
GR
ZIP/Postal Code
570 10
Country
Greece
Facility Name
Novartis Investigative Site
City
Athens
ZIP/Postal Code
GR 151 25
Country
Greece
Facility Name
Novartis Investigative Site
City
Athens
ZIP/Postal Code
GR-106 76
Country
Greece
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
1074
Country
Hungary
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
1085
Country
Hungary
Facility Name
Novartis Investigative Site
City
Ashkelon
ZIP/Postal Code
78278
Country
Israel
Facility Name
Novartis Investigative Site
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20132
Country
Italy
Facility Name
Novartis Investigative Site
City
Cefalù
State/Province
PA
ZIP/Postal Code
90015
Country
Italy
Facility Name
Novartis Investigative Site
City
Málaga
State/Province
Andalucia
ZIP/Postal Code
29010
Country
Spain
Facility Name
Novartis Investigative Site
City
Sevilla
State/Province
Andalucia
ZIP/Postal Code
41009
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Novartis Investigative Site
City
Basel
ZIP/Postal Code
4031
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
28856176
Citation
Derfuss T, Kovarik JM, Kappos L, Savelieva M, Chhabra R, Thakur A, Zhang Y, Wiendl H, Tomic D. alpha4-integrin receptor desaturation and disease activity return after natalizumab cessation. Neurol Neuroimmunol Neuroinflamm. 2017 Aug 25;4(5):e388. doi: 10.1212/NXI.0000000000000388. eCollection 2017 Sep.
Results Reference
derived

Learn more about this trial

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

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