MS Study Evaluating Safety and Efficacy of Two Doses of Fingolimod Versus Copaxone (ASSESS)

A 12-month, Randomized, Rater- and Dose-blinded Study to Compare the Efficacy and Safety of Fingolimod 0.25 mg and 0.5 mg Administered Orally Once Daily With Glatiramer Acetate 20 mg Administered Subcutaneously Once Daily in Patients With Relapsing-remitting Multiple Sclerosis

The purpose of this study was to demonstrate that at least one dose (0.5 mg followed by 0.25 mg) of fingolimod is superior to glatiramer acetate 20 mg SC in reducing the ARR up to 12 months in patients with relapsing-remitting MS

Study Overview

• Status: Terminated
• Conditions: Relapsing-remitting Multiple Sclerosis (RRMS)
• Intervention / Treatment: Drug: fingolimod; Drug: glatiramer acetate

Detailed Description

This was a multicenter, randomized, rater- and dose-blinded, study to compare the efficacy and safety of 0.25 mg and 0.5 mg of fingolimod with glatimer acetate 20 mg s.c. in patients with RRMS.

This study consisted of 3 periods:

• Screening Period: up to 45 days for all patients
• Treatment Period: 12 months of glatiramer acetate 20 mg, fingolimod 0.25 mg, or fingolimod 0.5 mg
• Follow-up occurred 3 months (12 weeks) after the last dose of study drug for all patients The informed consent form was signed prior to any study related activities at the screening visit. Randomization to either treatment group was preformed at visit 1 after a diligent check of applicable in- and exclusion criteria in a 1:1:1 ratio (changed to 5:3:2 after implementation of Amendment 2 in 2015).

Treatment groups:

• fingolimod 0.5 mg/day orally for up to 12 months
• fingolimod 0.25 mg/day orally for up to 12 months
• glatiramer acetate 20 mg/day subcutaneously for up to 12 months

• Study Type: Interventional
• Enrollment (Actual): 1064
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos aires, Argentina, C1015ABR
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1437JCP
      • Novartis Investigative Site
• Brazil
  • Campina Grande do Sul, Brazil, 83430 000
    • Novartis Investigative Site
  • Goiania, Brazil, 74605 020
    • Novartis Investigative Site
  • Passo Fundo, Brazil, 99010-080
    • Novartis Investigative Site
  • Rio de Janeiro, Brazil, 22610-350
    • Novartis Investigative Site
  • Sao Paulo, Brazil, 05651-901
    • Novartis Investigative Site
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150 221
      • Novartis Investigative Site
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
      • Novartis Investigative Site
  • SP
    • São Paulo, SP, Brazil, 08270-070
      • Novartis Investigative Site
  • Santa Catarina
    • Joinville, Santa Catarina, Brazil, 89202-165
      • Novartis Investigative Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6R 2B7
      • Novartis Investigative Site
  • British Columbia
    • Burnaby, British Columbia, Canada, V5G 2X6
      • Novartis Investigative Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 4K4
      • Novartis Investigative Site
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
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  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 5H6
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H1T 2M4
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H3A 2B4
      • Novartis Investigative Site
• Chile
  • Santiago, Chile, 8380815
    • Novartis Investigative Site
  • Santiago, Chile, PISO 1
    • Novartis Investigative Site
• Mexico
  • Aguascalientes, Mexico, 20127
    • Novartis Investigative Site
  • Chihuahua, Mexico, 31000
    • Novartis Investigative Site
  • Chihuahua, Mexico, 31203
    • Novartis Investigative Site
  • Monterrey, Mexico, 64460
    • Novartis Investigative Site
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 03310
      • Novartis Investigative Site
  • Edo De Mexico
    • Tlalnepantla, Edo De Mexico, Mexico, 54055
      • Novartis Investigative Site
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64000
      • Novartis Investigative Site
  • San Luis Potosí
    • San Luis Potosi, San Luis Potosí, Mexico, 78240
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• Puerto Rico
  • Guaynabo, Puerto Rico, 00968
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• United States
  • Alabama
    • Cullman, Alabama, United States, 35058
      • Novartis Investigative Site
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Novartis Investigative Site
    • Phoenix, Arizona, United States, 85013
      • Novartis Investigative Site
    • Phoenix, Arizona, United States, 85018
      • Novartis Investigative Site
    • Tucson, Arizona, United States, 85741
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  • California
    • Los Angeles, California, United States, 90089
      • Novartis Investigative Site
    • Sacramento, California, United States, 95817
      • Novartis Investigative Site
  • Colorado
    • Aurora, Colorado, United States, 80045
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    • Boulder, Colorado, United States, 80304
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    • Denver, Colorado, United States, 80220
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    • Fort Collins, Colorado, United States, 80528
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    • Loveland, Colorado, United States, 80538
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  • Connecticut
    • Fairfield, Connecticut, United States, 06824
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  • Delaware
    • Newark, Delaware, United States, 19713
      • Novartis Investigative Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
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  • Florida
    • Jacksonville, Florida, United States, 32209
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    • Maitland, Florida, United States, 32751
      • Novartis Investigative Site
    • Naples, Florida, United States, 34119
      • Novartis Investigative Site
    • New Port Richey, Florida, United States, 34653
      • Novartis Investigative Site
    • Orlando, Florida, United States, 32806
      • Novartis Investigative Site
    • Ormond Beach, Florida, United States, 32174
      • Novartis Investigative Site
    • Pompano Beach, Florida, United States, 33060
      • Novartis Investigative Site
    • Ponte Vedra Beach, Florida, United States, 32082-4627
      • Novartis Investigative Site
    • Port Charlotte, Florida, United States, 33952
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    • Sarasota, Florida, United States, 34243
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    • Tallahassee, Florida, United States, 32308
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    • Tampa, Florida, United States, 33609
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    • Vero Beach, Florida, United States, 32960
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    • West Palm Beach, Florida, United States, 33407
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  • Georgia
    • Atlanta, Georgia, United States, 30327
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  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Novartis Investigative Site
    • Evanston, Illinois, United States, 60201
      • Novartis Investigative Site
    • Flossmoor, Illinois, United States, 60422
      • Novartis Investigative Site
    • Northbrook, Illinois, United States, 60062
      • Novartis Investigative Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Novartis Investigative Site
    • Indianapolis, Indiana, United States, 46256
      • Novartis Investigative Site
  • Iowa
    • West Des Moines, Iowa, United States, 50314
      • Novartis Investigative Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Novartis Investigative Site
    • Lenexa, Kansas, United States, 66212
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  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Novartis Investigative Site
  • Louisiana
    • Hammond, Louisiana, United States, 70403
      • Novartis Investigative Site
    • New Orleans, Louisiana, United States, 70121
      • Novartis Investigative Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Novartis Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Novartis Investigative Site
    • Springfield, Massachusetts, United States, 01104
      • Novartis Investigative Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Novartis Investigative Site
    • Detroit, Michigan, United States, 48201
      • Novartis Investigative Site
    • Farmington Hills, Michigan, United States, 48334
      • Novartis Investigative Site
    • Grand Rapids, Michigan, United States, 49503
      • Novartis Investigative Site
    • Traverse City, Michigan, United States, 49684-2340
      • Novartis Investigative Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Novartis Investigative Site
    • Saint Louis, Missouri, United States, 63131
      • Novartis Investigative Site
    • Saint Louis, Missouri, United States, 63141
      • Novartis Investigative Site
    • Saint Louis, Missouri, United States, 63104
      • Novartis Investigative Site
  • Montana
    • Great Falls, Montana, United States, 59405
      • Novartis Investigative Site
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Novartis Investigative Site
  • New Jersey
    • Freehold, New Jersey, United States, 07728
      • Novartis Investigative Site
    • Newark, New Jersey, United States, 07103
      • Novartis Investigative Site
    • Teaneck, New Jersey, United States, 07666
      • Novartis Investigative Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Novartis Investigative Site
  • New York
    • Albany, New York, United States, 12208
      • Novartis Investigative Site
    • Amherst, New York, United States, 14226
      • Novartis Investigative Site
    • Buffalo, New York, United States, 14203
      • Novartis Investigative Site
    • Patchogue, New York, United States, 11772
      • Novartis Investigative Site
    • Rochester, New York, United States, 14642
      • Novartis Investigative Site
    • Stony Brook, New York, United States, 11794
      • Novartis Investigative Site
    • Syracuse, New York, United States, 13210
      • Novartis Investigative Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-9500
      • Novartis Investigative Site
    • Charlotte, North Carolina, United States, 28204
      • Novartis Investigative Site
    • Winston-Salem, North Carolina, United States, 27157
      • Novartis Investigative Site
  • Ohio
    • Akron, Ohio, United States, 44320
      • Novartis Investigative Site
    • Bellevue, Ohio, United States, 44811
      • Novartis Investigative Site
    • Columbus, Ohio, United States, 43210
      • Novartis Investigative Site
    • Columbus, Ohio, United States, 43221
      • Novartis Investigative Site
    • Dayton, Ohio, United States, 45408
      • Novartis Investigative Site
    • Toledo, Ohio, United States, 43614
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Novartis Investigative Site
    • Oklahoma City, Oklahoma, United States, 73112
      • Novartis Investigative Site
    • Tulsa, Oklahoma, United States, 74137
      • Novartis Investigative Site
  • Oregon
    • Portland, Oregon, United States, 97225
      • Novartis Investigative Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
      • Novartis Investigative Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29302
      • Novartis Investigative Site
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Novartis Investigative Site
    • Knoxville, Tennessee, United States, 37934
      • Novartis Investigative Site
    • Nashville, Tennessee, United States, 37205
      • Novartis Investigative Site
    • Nashville, Tennessee, United States, 37204
      • Novartis Investigative Site
  • Texas
    • Dallas, Texas, United States, 75214
      • Novartis Investigative Site
    • Houston, Texas, United States, 77030
      • Novartis Investigative Site
    • Round Rock, Texas, United States, 78681
      • Novartis Investigative Site
    • San Antonio, Texas, United States, 78258
      • Novartis Investigative Site
    • Sherman, Texas, United States, 75092
      • Novartis Investigative Site
  • Utah
    • Salt Lake City, Utah, United States, 84103
      • Novartis Investigative Site
  • Virginia
    • Alexandria, Virginia, United States, 22310
      • Novartis Investigative Site
    • Charlottesville, Virginia, United States, 22903
      • Novartis Investigative Site
    • Norfolk, Virginia, United States, 23507
      • Novartis Investigative Site
    • Richmond, Virginia, United States, 23226
      • Novartis Investigative Site
    • Roanoke, Virginia, United States, 24018
      • Novartis Investigative Site
  • Washington
    • Issaquah, Washington, United States, 98029
      • Novartis Investigative Site
    • Seattle, Washington, United States, 98101
      • Novartis Investigative Site
    • Seattle, Washington, United States, 98122-4379
      • Novartis Investigative Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Written informed consent must be obtained before any assessment is performed
• Male and female patients 18 to 65 years of age, inclusive.
• Patients with RRMS, as defined by 2010 revised McDonald criteria.
• Patients must be neurologically stable with no onset of relapse within 30 days of randomization
• Patients with at least 1 documented relapse during the previous year or 2 documented relapses during the previous 2 years before randomization.
• Patients with an EDSS score of 0 to 6, inclusive, at Screening. A score of 6.0 indicates unilateral assistance (cane or crutch) required to walk at least 100 meters with or without resting.

Exclusion criteria:

• Patients with a history of malignancy of any organ system (other than cutaneous basal cell carcinoma) in the last 5 years that do not have confirmation of absence of a malignancy prior to randomization
• Patients with an active chronic disease (or stable but treated with immune therapy) of the immune system other than MS (e.g., rheumatoid arthritis, scleroderma, Sjogren's syndrome, Crohn's disease, ulcerative colitis) or with a known immunodeficiency syndrome (HIV-antibody positive, AIDS, hereditary immune deficiency, drug-induced immune deficiency).
• Patients who have been treated with:
• High-dose intravenous (IV) immunoglobulin (Ig) within 4 weeks before randomization
• Immunosuppressive/chemotherapeutic medications (e.g., azathioprine, cyclophosphamide, methotrexate) within 6 months before randomization
• Natalizumab within 2 months before randomization
• Previous treatment with lymphocyte-depleting therapies (e.g., rituximab, alemtuzumab, ofatumumab, ocrelizumab, or cladribine) within 1 year before randomization Previous treatment with mitoxantrone within 6 months before randomization
• Use of teriflunomide within 3.5 months prior to randomization, except if active washout (with either cholestyramine or activated charcoal) was done. In that case, plasma levels are required to be measured and be below 0.02 mg/L before randomization.

No washout period is necessary for patients treated with dimethyl fumarate, interferon (IFN) beta, or glatiramer acetate.

Patients being treated with dimethyl fumarate, glatiramer acetate, or IFN beta at the Screening visit can continue drug intake up to the day before Day 1 of this study (i.e., there is no need for a washout period).

• Patients who have been treated with systemic corticosteroids or adrenocorticotropic hormones in the past 30 days prior to the screening magnetic resonance imaging (MRI) procedure.
• Patients with uncontrolled diabetes mellitus (glycosylated hemoglobin >9%) or with diabetic neuropathy.
• Patients with a diagnosis of macular edema during Screening (patients with a history of macular edema will be allowed to enter the study provided that they do not have macular edema at Screening).
• Patients with severe active bacterial, viral, or fungal infections.
• Patients without acceptable evidence of immunity to varicella zoster virus (VZV) at randomization.
• Patients who have received any live or live-attenuated vaccines (including VZV, herpes simplex, or measles) within 1 month before randomization.
• Patients who have received total lymphoid irradiation or bone marrow transplantation.
• Patients with any unstable medical/psychiatric condition, as assessed by the primary treating physician at each site.
• Patients who in the last 6 months experienced any of the following cardiovascular conditions or findings in the screening electrocardiogram (ECG): myocardial infarction, unstable angina, stroke, transient ischemic attack or decompensated heart failure requiring hospitalization or Class III/IV heart failure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: fingolimod 0.5 mg; orally once daily	Drug: fingolimod; capsule; Other Names: Gilenya; FTY720, fingolimod hydrochloride,
EXPERIMENTAL: fingolimod 0.25mg; orally once daily	Drug: fingolimod; capsule; Other Names: Gilenya; FTY720, fingolimod hydrochloride,
ACTIVE_COMPARATOR: glatiramer acetate 20 mg; subcutaneous once daily	Drug: glatiramer acetate; subcutaneous injection; Other Names: Copaxone, Glatopa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Annualized Relapse Rate	Annualized relapse rate (ARR) was defined as the average number of confirmed relapses per year (i.e., the total number of confirmed relapses divided by the total days in the study multiplied by 365.25). The number of relapses included all the confirmed relapses experienced during the study from first dose to end of study.	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New or Newly Enlarging T2 Lesions	Inflammatory activity based on MRI measurement of new/newly enlarged T2 lesion count.	At 12 months/end of study
Number of Participants Free of New/Newly Enlarged T2 Lesions	Inflammatory activity based on MRI measurement of new/newly enlarged T2 lesion count.	At 12 months/end of study
Change From Baseline in T2 Lesion Volume	Inflammatory activity based on MRI measurement of new/newly enlarged T2 lesion volume	Baseline, 12 months/end of study
Gd Enhancing T1 Lesion Count	Inflammatory activity based on MRI measurement of Gd enhancing T1 lesion count	At 12 months/end of study
Gd Enhancing T1 Lesion Volume	Inflammatory activity based on MRI measurement of Gd enhancing T1 lesion count	Baseline, 12 months/end of study
Percentage of Patients Free of New T1 Hypointense Lesions	Based on MRI measures of new T1 hypointense lesions	12 months
Change From Baseline in TSQM Scales	Treatment Satisfaction Questionnaire for Medication (TSQM) was developed and validated as a general measure for treatment satisfaction. Each scale score was calculated by summing individual items and then transformed to a 0-100 scale. Higher summary scores indicate better satisfaction with study drug.	6 months, 12 months/end of study
Percent Brain Volume Change From Baseline	Using a Central MRI vendor to ensure calibrated MRI scanning equipment across all sites, MRI scans were performed on subjects following the established parameters and transferred to the central vendor for review of quality and assessment/evaluation.	Baseline, 12 months, end of study

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Cree BAC, Goldman MD, Corboy JR, Singer BA, Fox EJ, Arnold DL, Ford C, Weinstock-Guttman B, Bar-Or A, Mientus S, Sienkiewicz D, Zhang Y, Karan R, Tenenbaum N; ASSESS Trial Investigators. Efficacy and Safety of 2 Fingolimod Doses vs Glatiramer Acetate for the Treatment of Patients With Relapsing-Remitting Multiple Sclerosis: A Randomized Clinical Trial. JAMA Neurol. 2020 Aug 24;78(1):1-13. doi: 10.1001/jamaneurol.2020.2950. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 9, 2012
• Primary Completion (ACTUAL): April 30, 2018
• Study Completion (ACTUAL): April 30, 2018

Study Registration Dates

• First Submitted: June 29, 2012
• First Submitted That Met QC Criteria: July 3, 2012
• First Posted (ESTIMATE): July 4, 2012

Study Record Updates

• Last Update Posted (ACTUAL): May 28, 2019
• Last Update Submitted That Met QC Criteria: April 29, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• 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; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Adjuvants, Immunologic; Sphingosine 1 Phosphate Receptor Modulators; Fingolimod Hydrochloride; Glatiramer Acetate; (T,G)-A-L
• Other Study ID Numbers: CFTY720D2312

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com