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

• ClinicalTrials.gov Identifier: NCT01499667
• Recruitment Status: Terminated
• First Posted: December 26, 2011
• Results First Posted: April 4, 2014
• Last Update Posted: August 8, 2014
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Relapsing Remitting Multiple Sclerosis (RRMS)	Drug: Fingolimod; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 142 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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)
• Study Start Date: September 2011
• Actual Primary Completion Date: November 2012
• Actual Study Completion Date: November 2012

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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
6. 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.
7. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

Australia, Victoria

Novartis Investigative Site

Box Hill, Victoria, Australia, 3128

Novartis Investigative Site

Heidelberg, Victoria, Australia, 3084

Austria

Novartis Investigative Site

Vienna, Austria, 1010

Czech Republic

Novartis Investigative Site

Prague 5, Czech Republic, 150 00

Novartis Investigative Site

Praha 2, Czech Republic, 128 08

Novartis Investigative Site

Teplice, Czech Republic, 415 29

Finland

Novartis Investigative Site

Helsinki, Finland, 00100

Germany

Novartis Investigative Site

Ostfildern, Baden-Wuerttemberg, Germany, 73760

Novartis Investigative Site

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

Greece

Novartis Investigative Site

Athens, GR, Greece, 115 25

Novartis Investigative Site

Ioannina, GR, Greece, 455 00

Novartis Investigative Site

Thessaloniki, GR, Greece, 570 10

Novartis Investigative Site

Athens, Greece, GR 151 25

Novartis Investigative Site

Athens, Greece, GR-106 76

Hungary

Novartis Investigative Site

Budapest, Hungary, 1074

Novartis Investigative Site

Budapest, Hungary, 1085

Israel

Novartis Investigative Site

Ashkelon, Israel, 78278

Novartis Investigative Site

Jerusalem, Israel, 91120

Italy

Novartis Investigative Site

Milano, MI, Italy, 20132

Novartis Investigative Site

Cefalù, PA, Italy, 90015

Spain

Novartis Investigative Site

Málaga, Andalucia, Spain, 29010

Novartis Investigative Site

Sevilla, Andalucia, Spain, 41009

Novartis Investigative Site

Barcelona, Catalunya, Spain, 08035

Novartis Investigative Site

Barcelona, Spain, 08025

Novartis Investigative Site

Madrid, Spain, 28046

Switzerland

Novartis Investigative Site

Basel, Switzerland, 4031

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Derfuss T, Kovarik JM, Kappos L, Savelieva M, Chhabra R, Thakur A, Zhang Y, Wiendl H, Tomic D. α4-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.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01499667
• Other Study ID Numbers: CFTY720D2324; 2011-001442-15 ( EudraCT Number )
• First Posted: December 26, 2011
• Results First Posted: April 4, 2014
• Last Update Posted: August 8, 2014
• Last Verified: August 2014

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

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; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Fingolimod Hydrochloride; Sphingosine 1 Phosphate Receptor Modulators; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs