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

Relapsing-remitting Multiple Sclerosis (RRMS) Clinical Trial

— ASSESS  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01633112
• Other study ID #: CFTY720D2312
• Status: Terminated
• Phase: Phase 3
• Start date: August 9, 2012
• Est. completion date: April 30, 2018

Study information

• Verified date: April 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1064
• Est. completion date: April 30, 2018
• Est. primary completion date: April 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• fingolimod
capsule
• glatiramer acetate
subcutaneous injection

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Brazil	Novartis Investigative Site	Belo Horizonte	Minas Gerais
Brazil	Novartis Investigative Site	Campina Grande do Sul
Brazil	Novartis Investigative Site	Goiania
Brazil	Novartis Investigative Site	Joinville	Santa Catarina
Brazil	Novartis Investigative Site	Passo Fundo
Brazil	Novartis Investigative Site	Porto Alegre	Rio Grande Do Sul
Brazil	Novartis Investigative Site	Rio de Janeiro
Brazil	Novartis Investigative Site	Sao Paulo
Brazil	Novartis Investigative Site	São Paulo	SP
Canada	Novartis Investigative Site	Burnaby	British Columbia
Canada	Novartis Investigative Site	Chicoutimi	Quebec
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Halifax	Nova Scotia
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Ottawa	Ontario
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Santiago
Mexico	Novartis Investigative Site	Aguascalientes
Mexico	Novartis Investigative Site	Chihuahua
Mexico	Novartis Investigative Site	Chihuahua
Mexico	Novartis Investigative Site	Mexico	Distrito Federal
Mexico	Novartis Investigative Site	Monterrey
Mexico	Novartis Investigative Site	Monterrey	Nuevo León
Mexico	Novartis Investigative Site	San Luis Potosi	San Luis Potosí
Mexico	Novartis Investigative Site	Tlalnepantla	Edo De Mexico
Puerto Rico	Novartis Investigative Site	Guaynabo
United States	Novartis Investigative Site	Akron	Ohio
United States	Novartis Investigative Site	Albany	New York
United States	Novartis Investigative Site	Albuquerque	New Mexico
United States	Novartis Investigative Site	Alexandria	Virginia
United States	Novartis Investigative Site	Amherst	New York
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Aurora	Colorado
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Bellevue	Ohio
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Boulder	Colorado
United States	Novartis Investigative Site	Buffalo	New York
United States	Novartis Investigative Site	Chapel Hill	North Carolina
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Charlottesville	Virginia
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Cordova	Tennessee
United States	Novartis Investigative Site	Cullman	Alabama
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Dayton	Ohio
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Elk Grove Village	Illinois
United States	Novartis Investigative Site	Evanston	Illinois
United States	Novartis Investigative Site	Fairfield	Connecticut
United States	Novartis Investigative Site	Farmington Hills	Michigan
United States	Novartis Investigative Site	Flossmoor	Illinois
United States	Novartis Investigative Site	Fort Collins	Colorado
United States	Novartis Investigative Site	Freehold	New Jersey
United States	Novartis Investigative Site	Grand Rapids	Michigan
United States	Novartis Investigative Site	Great Falls	Montana
United States	Novartis Investigative Site	Hammond	Louisiana
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Issaquah	Washington
United States	Novartis Investigative Site	Jacksonville	Florida
United States	Novartis Investigative Site	Kansas City	Kansas
United States	Novartis Investigative Site	Kansas City	Missouri
United States	Novartis Investigative Site	Knoxville	Tennessee
United States	Novartis Investigative Site	Las Vegas	Nevada
United States	Novartis Investigative Site	Lenexa	Kansas
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Louisville	Kentucky
United States	Novartis Investigative Site	Loveland	Colorado
United States	Novartis Investigative Site	Maitland	Florida
United States	Novartis Investigative Site	Milwaukee	Wisconsin
United States	Novartis Investigative Site	Naples	Florida
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	New Orleans	Louisiana
United States	Novartis Investigative Site	New Port Richey	Florida
United States	Novartis Investigative Site	Newark	Delaware
United States	Novartis Investigative Site	Newark	New Jersey
United States	Novartis Investigative Site	Norfolk	Virginia
United States	Novartis Investigative Site	Northbrook	Illinois
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Orlando	Florida
United States	Novartis Investigative Site	Ormond Beach	Florida
United States	Novartis Investigative Site	Patchogue	New York
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Pompano Beach	Florida
United States	Novartis Investigative Site	Ponte Vedra Beach	Florida
United States	Novartis Investigative Site	Port Charlotte	Florida
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	Roanoke	Virginia
United States	Novartis Investigative Site	Rochester	New York
United States	Novartis Investigative Site	Round Rock	Texas
United States	Novartis Investigative Site	Sacramento	California
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	Salt Lake City	Utah
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	Sarasota	Florida
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Sherman	Texas
United States	Novartis Investigative Site	Spartanburg	South Carolina
United States	Novartis Investigative Site	Springfield	Massachusetts
United States	Novartis Investigative Site	Stony Brook	New York
United States	Novartis Investigative Site	Syracuse	New York
United States	Novartis Investigative Site	Tallahassee	Florida
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Teaneck	New Jersey
United States	Novartis Investigative Site	Toledo	Ohio
United States	Novartis Investigative Site	Traverse City	Michigan
United States	Novartis Investigative Site	Tucson	Arizona
United States	Novartis Investigative Site	Tulsa	Oklahoma
United States	Novartis Investigative Site	Vero Beach	Florida
United States	Novartis Investigative Site	Washington	District of Columbia
United States	Novartis Investigative Site	West Des Moines	Iowa
United States	Novartis Investigative Site	West Palm Beach	Florida
United States	Novartis Investigative Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Chile,  Mexico,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Gd Enhancing T1 Lesion Count	Inflammatory activity based on MRI measurement of Gd enhancing T1 lesion count	At 12 months/end of study
Secondary	Gd Enhancing T1 Lesion Volume	Inflammatory activity based on MRI measurement of Gd enhancing T1 lesion count	Baseline, 12 months/end of study
Secondary	Percentage of Patients Free of New T1 Hypointense Lesions	Based on MRI measures of new T1 hypointense lesions	12 months
Secondary	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
Secondary	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