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

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 Intervention Model: Parallel Assignment Masking: Double Blind (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)

Resource links provided by NLM:

Genetics Home Reference related topics: multiple sclerosis

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Fingolimod Fingolimod hydrochloride Natalizumab

U.S. FDA Resources

Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

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 ]
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) ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 (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

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

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Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators


Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals

More Information


Responsible Party:	Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01499667 History of Changes
Other Study ID Numbers:	CFTY720D2324 2011-001442-15 ( EudraCT Number )
Study First Received:	August 18, 2011
Results First Received:	November 25, 2013
Last Updated:	August 6, 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:


Sclerosis Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting Pathologic Processes Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases	Autoimmune Diseases Immune System Diseases Natalizumab Fingolimod Hydrochloride Immunologic Factors Physiological Effects of Drugs Immunosuppressive Agents

ClinicalTrials.gov processed this record on July 21, 2017

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