Efficacy of Fingolimod in de Novo Patients Versus Fingolimod in Patients Previously Treated With a First Line Disease Modifying Therapy (EARLiMS)

A Multi-centre, Open-label, Non-randomised, Parallel Group Clinical Trial to Assess the Efficacy of Fingolimod in Naive Patients Versus Fingolimod in Patients Previously Treated With Interferons or Glatiramer Acetate, Based on the Presence of Relapses in Patients With Relapsing-remitting Multiple Sclerosis.

This study assessed the efficacy of fingolimod in patients with short duration relapsing-remitting multiple sclerosis who had not been previously treated with disease-modifying therapies (DMTs), versus patients with the same disease duration who had previously received first-line DMTs.

Study Overview

• Status: Completed
• Conditions: Relapsing Remitting Multiple Sclerosis
• Intervention / Treatment: Drug: Fingolimod (FTY720)

• Study Type: Interventional
• Enrollment (Actual): 347
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Bedford Park, Australia, SA 5042
    • Novartis Investigative Site
  • Brisbane Queensland, Australia, 4029
    • Novartis Investigative Site
  • Geelong VIC, Australia, 3220
    • Novartis Investigative Site
  • New South Wales
    • East Gosford, New South Wales, Australia, 2250
      • Novartis Investigative Site
    • Kanwal, New South Wales, Australia, 2259
      • Novartis Investigative Site
    • Liverpool, New South Wales, Australia, 2170
      • Novartis Investigative Site
    • New Lambton Heights, New South Wales, Australia, 2305
      • Novartis Investigative Site
    • Sydney, New South Wales, Australia, 2050
      • Novartis Investigative Site
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Novartis Investigative Site
  • South Australia
    • Adelaide, South Australia, Australia
      • Novartis Investigative Site
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Novartis Investigative Site
    • Fitzroy, Victoria, Australia, 3011
      • Novartis Investigative Site
    • Melbourne, Victoria, Australia, 3000
      • Novartis Investigative Site
    • Parkville, Victoria, Australia, 3050
      • Novartis Investigative Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Las Palmas de Gran Canaria, Spain, 35016
    • Novartis Investigative Site
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Madrid, Spain, 28006
    • Novartis Investigative Site
  • Madrid, Spain, 28007
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Santa Cruz de Tenerife, Spain, 38009
    • Novartis Investigative Site
  • A Coruna
    • Ferrol, A Coruna, Spain, 15405
      • Novartis Investigative Site
  • Andalucia
    • Córdoba, Andalucia, Spain, 14004
      • Novartis Investigative Site
    • Granada, Andalucia, Spain, 18012
      • Novartis Investigative Site
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41009
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41014
      • Novartis Investigative Site
  • Asturias
    • Oviedo, Asturias, Spain, 33006
      • Novartis Investigative Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Novartis Investigative Site
  • Castilla La Mancha
    • Albacete, Castilla La Mancha, Spain, 02006
      • Novartis Investigative Site
  • Castilla Y Leon
    • Valladolid, Castilla Y Leon, Spain, 47011
      • Novartis Investigative Site
  • Castilla Y León
    • Leon, Castilla Y León, Spain, 24080
      • Novartis Investigative Site
  • Catalunya
    • Badalona, Catalunya, Spain, 08916
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
  • Cataluña
    • Tarragona, Cataluña, Spain, 43007
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46026
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46017
      • Novartis Investigative Site
  • Galicia
    • La Coruna, Galicia, Spain, 15006
      • Novartis Investigative Site
  • Islas Baleares
    • Palma De Mallorca, Islas Baleares, Spain, 07120
      • Novartis Investigative Site
  • Las Palmas De G.C
    • Las Palmas de Gran Canaria, Las Palmas De G.C, Spain, 35010
      • Novartis Investigative Site
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Novartis Investigative Site
  • Pais Vasco
    • Barakaldo, Pais Vasco, Spain, 48903
      • Novartis Investigative Site
    • Bilbao, Pais Vasco, Spain, 48013
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients diagnosed with multiple sclerosis, according to the 2010 revised McDonald criteria, with a relapsing-remitting course, and with at least 9 T2 lesions consistent with the disease, with disease duration greater than or equal to one year and less than or equal to five years.
• Patients who have had at least two relapses in the past two years and an Expanded Disability Status Scale score between 0 and 3.5, inclusive.

Patients

• Treatment naïve: patients who have never been treated with a Disease Modifying Therapy or
• Previously treated with a first-line Disease Modifying Therapy

Exclusion Criteria:

• Patients who have received treatment with:

Fingolimod at any time (e.g. participation in a fingolimod clinical trial), Immunosuppressant drugs such as azathioprine or methotrexate at any time; Immunoglobulins in the past 6 months. Monoclonal antibodies including natalizumab, Cladribine, cyclophosphamide or mitoxantrone, at any time.

- Other protocol defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Naive or de novo participants; Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.	Drug: Fingolimod (FTY720); Hard gelatin capsules containing 0.5 mg of fingolimod.
EXPERIMENTAL: Previously treated with first-line DMTs participants; Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months.	Drug: Fingolimod (FTY720); Hard gelatin capsules containing 0.5 mg of fingolimod.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annual Relapse Rate (ARR)	ARR = 365 days * number of relapses / total days taking the study medication.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Relapse	Time to first relapse was defined as the time from the first day of treatment to the first day of a new neurological symptom or worsening of an existing one.	first day of treatment to the first day of a new neurological symptom or worsening of an existing one, up to 12 months
Change From Baseline in Expanded Disability Status Scale (EDSS) Score	The EDSS is an ordinal clinical rating scale ranging from a total score of 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. A negative change from baseline indicates improvement.	baseline, 12 months
Change From Baseline in Cerebral Volume	Cerebral volume was assessed by magnetic resonance imaging (MRI). A negative change from baseline indicates improvement.	baseline, 12 months
Percentage of Participants With Mild, Moderate or Severe Relapse	The investigator classified a relapse as moderate-severe if oral or intravenous (IV) treatment (according to the local clinical practice) with steroids and/or hospitalization was needed. If neither oral nor IV treatment with steroids nor hospitalization was needed, the relapse was considered as mild.	12 months
Percentage of Relapse-free Participants	Relapse-free participants were defined as participants who experienced no new neurological symptom or worsening of an existing one (relapses) during the 12-month treatment period with 0.5 mg fingolimod.	12 months
Mean Number of T2 Active Lesions	The mean number of new or enlarged T2 active lesions was assessed by MRI.	12 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 24, 2011
• Primary Completion (ACTUAL): December 26, 2015
• Study Completion (ACTUAL): December 26, 2015

Study Registration Dates

• First Submitted: December 19, 2011
• First Submitted That Met QC Criteria: December 22, 2011
• First Posted (ESTIMATE): December 26, 2011

Study Record Updates

• Last Update Posted (ACTUAL): January 25, 2019
• Last Update Submitted That Met QC Criteria: August 15, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Fingolimod; Relapsing Remitting Multiple Sclerosis; Early multiple sclerosis; Naive patients
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Sphingosine 1 Phosphate Receptor Modulators; Fingolimod Hydrochloride
• Other Study ID Numbers: CFTY720DES03; 2011-003484-30 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No