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

Relapsing Remitting Multiple Sclerosis (RRMS) Clinical Trial

— 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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01499667
• Other study ID #: CFTY720D2324
• Secondary ID: 2011-001442-15
• Status: Terminated
• Phase: Phase 3
• First received: August 18, 2011
• Last updated: August 6, 2014
• Start date: September 2011
• Est. completion date: November 2012

Study information

• Verified date: August 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Federal Institute for Drugs and Medical DevicesUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyEuropean Union: European Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 142
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing Remitting Multiple Sclerosis (RRMS)
• Sclerosis

Intervention

Drug:
• Fingolimod
Fingolimod 0.5 mg capsules for oral administration once daily
• Placebo
Matching placebo in capsules for oral administration once daily.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Box Hill	Victoria
Australia	Novartis Investigative Site	Heidelberg	Victoria
Austria	Novartis Investigative Site	Vienna
Czech Republic	Novartis Investigative Site	Prague 5
Czech Republic	Novartis Investigative Site	Praha 2
Czech Republic	Novartis Investigative Site	Teplice
Finland	Novartis Investigative Site	Helsinki
Germany	Novartis Investigative Site	Bad Mergentheim
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bielefeld
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Celle
Germany	Novartis Investigative Site	Erbach
Germany	Novartis Investigative Site	Erfurt
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Itzehoe
Germany	Novartis Investigative Site	Kandel
Germany	Novartis Investigative Site	Krefeld
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Münster
Germany	Novartis Investigative Site	Neuburg
Germany	Novartis Investigative Site	Neuruppin
Germany	Novartis Investigative Site	Ostfildern	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Rüdersdorf
Germany	Novartis Investigative Site	Siegen
Germany	Novartis Investigative Site	Ulm
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Ioannina	GR
Greece	Novartis Investigative Site	Thessaloniki	GR
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Israel	Novartis Investigative Site	Ashkelon
Israel	Novartis Investigative Site	Jerusalem
Italy	Novartis Investigative Site	Cefalù	PA
Italy	Novartis Investigative Site	Milano	MI
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Málaga	Andalucia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Switzerland	Novartis Investigative Site	Basel

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Australia,  Austria,  Czech Republic,  Finland,  Germany,  Greece,  Hungary,  Israel,  Italy,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Number of active T2 lesions from last natalizumab dose through 8 weeks of fingolimod treatment	No
Secondary	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.	8, 12 and 16 weeks (number of active T2 lesions during the washout period only)	No
Secondary	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 T2 lesions during 8 wks of fingolimod treatment	No
Secondary	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.	Baseline up to 24 weeks	No
Secondary	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.	Baseline to week 16 and week 32	No
Secondary	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	8 weeks and 24 weeks	No
Secondary	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.	Baseline to maximum of 16 weeks	Yes
Secondary	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.	Baseline to maximum of 16 weeks	Yes