An Extension Study of the Efficacy and Safety of Fingolimod (FTY720) in Patients With Relapsing Multiple Sclerosis

• ClinicalTrials.gov Identifier: NCT00670449
• Recruitment Status: Completed
• First Posted: May 1, 2008
• Results First Posted: September 4, 2013
• Last Update Posted: September 4, 2013
• Sponsor: Novartis
• Collaborator: Mitsubishi Tanabe Pharma Corporation
• Information provided by (Responsible Party): Novartis

Study Description

Brief Summary:

This study was an extension study of NCT00537082. This study was designed to evaluate the efficacy and safety of long-term administration of 0.5 mg or 1.25 mg of fingolimod (FTY720) to relapsing multiple sclerosis.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis	Drug: Fingolimod	Phase 2

Detailed Description:

A decision was made to switch all patients on fingolimod 1.25 mg/day to fingolimod 0.5 mg/day in an amendment to the study protocol. The study became open-label with all patients receiving fingolimod 0.5 mg/day on 22 Feb 2010.

The efficacy data for Months 0-6 in this study report is from the core study NCT00537082.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 143 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An Extension of the 6-month, Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Study Comparing Efficacy and Safety of FTY720 0.5 mg and 1.25 mg Administered Orally Once Daily in Patients With Relapsing Multiple Sclerosis
• Study Start Date: April 2008
• Actual Primary Completion Date: April 2012
• Actual Study Completion Date: April 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Fingolimod 0.5 mg; Patients who received fingolimod 0.5 orally once daily in the core study continued on the same dose in this extension study.	Drug: Fingolimod; Fingolimod was supplied in capsules.; Other Names: Gilenya; Imsera
Experimental: Fingolimod 1.25 mg; Patients who received fingolimod 1.25 mg orally once daily in the core study continued on the same dose in this extension study.	Drug: Fingolimod; Fingolimod was supplied in capsules.; Other Names: Gilenya; Imsera
Experimental: Placebo-fingolimod; Patients who were randomized to placebo in the core study were re-randomized to either fingolimod 0.5 or 1.25 mg (1:1) orally once daily in this extension study.	Drug: Fingolimod; Fingolimod was supplied in capsules.; Other Names: Gilenya; Imsera

Outcome Measures

Primary Outcome Measures :

1. Percentage of Patients Free of Gd-enhanced T1 Weighted Magnetic Resonance Imaging (MRI) Lesions [ Time Frame: Months 6, 9, 12, 18, 24, 36, and 48 ]
   To ensure consistency, MRI scans were evaluated centrally at the Institute of Neurotherapeutics in Kyoto, Japan. After checking the scans for completeness and quality, all scans were analyzed by blinded readers (experienced neurologists). The number of Gd-enhanced T1 weighted MRI lesions were counted and recorded. Lesions expanding through several slices were counted as only 1 lesion.

Secondary Outcome Measures :

1. Percentage of Patients Free of New or Newly Enlarged T2 Weighted MRI Lesions [ Time Frame: Months 0-3, 3-6, 6-9, 9-12, 12-18, 18-24, 24-36,36-48, and 48 to the end of the study (up to 4 years) ]
   To ensure consistency, MRI scans were evaluated centrally at the Institute of Neurotherapeutics in Kyoto, Japan. After checking the scans for completeness and quality, all scans were analyzed by blinded readers (experienced neurologists). The number of new or newly enlarged T2 weighted MRI lesions were counted and recorded. New lesions were identified by comparing each lesion with previous scans. Lesions expanding through several slices were counted as only 1 lesion.
2. Aggregate Annualized Relapse Rate (ARR) Based on Confirmed Relapses [ Time Frame: Months 0-6, 6-12, 12-24, 24-36, 36-48, and 48 to the end of the study (up to 4 years) ]
   The ARR was defined as the total number of relapses for all patients in the treatment arm / total number of days in the study for all patients in the treatment arm for the specific period of time × 365.25. General definition of relapse: Appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from the onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (< 37.5°C) or infection. A relapse was to be confirmed by a neurologist trained on the Expanded Disability Status Scale (EDSS). A relapse must be accompanied by an increase of at least half a step (0.5) on the EDSS or an increase of 1 point on 2 different Functional Systems (FS) of the EDSS or 2 points on 1 of the FS (excluding Bowel/Bladder or Cerebral FS).
3. Percentage of Patients Relapse-free at the End of the Study [ Time Frame: Baseline to the end of the study (up to 4 years) ]
   Patients who did not experience any relapses confirmed by a neurologist during the study were regarded as relapse-free patients.
4. Percentage of Patients Free From 3-month and 6-month Confirmed Disability Progression at Their Last Expanded Disability Status Scale (EDSS) Assessment [ Time Frame: Baseline to the end of the study (up to 4 years) ]
   Disability progression was measured by the EDSS score. A trained neurologist grades the multiple sclerosis (MS) disability of the patient on a scale of 0-5 (no to severe disability) in 8 Functional Systems (FS): Pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral (or mental), and other. The EDSS score ranges from 0-10 (normal to dead) with higher scores indicating greater disability. A 3-month confirmed disability progression was defined as a 3-month sustained increase from baseline in the EDSS score, that is, every EDSS score obtained (scheduled or unscheduled) within 3-months after the first progression met the following progression criteria: One point (1) increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point (0.5) increase in patients with baseline EDSS score of 5.5 or above. A 6-month confirmed disability progression was defined exactly the same except that the sustained progression had to last 6 months.
5. Change From Core Study Baseline in the Expanded Disability Status Scale (EDSS) Score [ Time Frame: Baseline to Months 12, 24, 36, 48, and end of study (up to 4 years) ]
   Disability progression was measured by the EDSS score. A trained neurologist grades the multiple sclerosis (MS) disability of the patient on a scale of 0-5 (no to severe disability) in 8 Functional Systems (FS): Pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral (or mental), and other. The EDSS score ranges from 0-10 (normal to dead) with higher scores indicating greater disability. A 3-month confirmed disability progression was defined as a 3-month sustained increase from baseline in the EDSS score, that is, every EDSS score obtained (scheduled or unscheduled) within 3-months after the first progression met the following progression criteria: One point (1) increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point (0.5) increase in patients with baseline EDSS score of 5.5 or above. A 6-month confirmed disability progression was defined exactly the same except that the sustained progression had to last 6 months.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients who completed 6 months of treatment with the study drug and the Month 6 visit in the core study NCT00537082.
• Females of childbearing potential who have a negative pregnancy test in the core study NCT00537082.

Exclusion Criteria:

• Patients who permanently discontinued study drug treatment prior to the Month 6 visit in the core study NCT00537082.

Other protocol-defined inclusion/exclusion criteria applied to the study.

Contacts and Locations

Locations

Japan

Novartis Investigative Site

Chiba, Japan, 276-8524

Novartis Investigative Site

Ehime, Japan, 791-0295

Novartis Investigative Site

Fukuoka, Japan, 807-8555

Novartis Investigative Site

Gunma, Japan, 371-8511

Novartis Investigative Site

Hyogo, Japan, 650-0017

Novartis Investigative Site

Ibaraki, Japan, 305-8576

Novartis Investigative Site

Kanagawa, Japan, 259-1193

Novartis Investigative Site

Kyoto, Japan, 604-8453

Novartis Investigative Site

Kyoto, Japan, 616-8255

Novartis Investigative Site

Morioka, Japan, 020-8505

Novartis Investigative Site

Niigata, Japan, 951-8520

Novartis Investigative Site

Osaka, Japan, 556-0016

Novartis Investigative Site

Osaka, Japan, 589-8511

Novartis Investigative Site

Osaka, Japan

Novartis Investigative Site

Sapporo, Japan, 060-8648

Novartis Investigative Site

Tochigi, Japan, 329-0498

Novartis Investigative Site

Tokyo, Japan, 113-8519

Novartis Investigative Site

Tokyo, Japan, 145-0065

Novartis Investigative Site

Tokyo, Japan, 162-8666

Novartis Investigative Site

Wakayama, Japan, 641-8510

Sponsors and Collaborators

Novartis

Mitsubishi Tanabe Pharma Corporation

Investigators

• Principal Investigator: Novartis Pharmaceuticals, Japan; 81-3-3797-8748

More Information

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

Saida T, Itoyama Y, Kikuchi S, Hao Q, Kurosawa T, Ueda K, Auberson LZ, Tsumiyama I, Nagato K, Kira JI. Long-term efficacy and safety of fingolimod in Japanese patients with relapsing multiple sclerosis: 3-year results of the phase 2 extension study. BMC Neurol. 2017 Jan 28;17(1):17. doi: 10.1186/s12883-017-0794-5.

Kira J, Itoyama Y, Kikuchi S, Hao Q, Kurosawa T, Nagato K, Tsumiyama I, von Rosenstiel P, Zhang-Auberson L, Saida T. Fingolimod (FTY720) therapy in Japanese patients with relapsing multiple sclerosis over 12 months: results of a phase 2 observational extension. BMC Neurol. 2014 Jan 29;14:21. doi: 10.1186/1471-2377-14-21.

• Responsible Party: Novartis
• ClinicalTrials.gov Identifier: NCT00670449
• Other Study ID Numbers: CFTY720D1201E1
• First Posted: May 1, 2008
• Results First Posted: September 4, 2013
• Last Update Posted: September 4, 2013
• Last Verified: June 2013

Keywords provided by Novartis:

FTY720; multiple sclerosis; MS

Additional relevant MeSH terms:

Multiple Sclerosis; 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; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs