Clinical trial NCT01633112: MS Study Evaluating Safety and Efficacy of Two Doses of Fingolimod Versus Copaxone
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Relapsing-remitting Multiple Sclerosis (RRMS)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-07-04
Enrollment: 1064
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

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

Eligibility criteria: 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.

Primary outcomes:
measure: Confirmed Annualized Relapse Rate
timeFrame: up to 12 months
Secondary outcomes:
measure: New or Newly Enlarging T2 Lesions
timeFrame: At 12 months/end of study
measure: Number of Participants Free of New/Newly Enlarged T2 Lesions
timeFrame: At 12 months/end of study
measure: Change From Baseline in T2 Lesion Volume
timeFrame: Baseline, 12 months/end of study
measure: Gd Enhancing T1 Lesion Count
timeFrame: At 12 months/end of study
measure: Gd Enhancing T1 Lesion Volume
timeFrame: Baseline, 12 months/end of study
measure: Percentage of Patients Free of New T1 Hypointense Lesions
timeFrame: 12 months
measure: Change From Baseline in TSQM Scales
timeFrame: 6 months, 12 months/end of study
measure: Percent Brain Volume Change From Baseline
timeFrame: Baseline, 12 months, end of study
Other outcomes:
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country: United States
facility: Novartis Investigative Site
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state: Connecticut
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state: Delaware
city: Washington
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facility: Novartis Investigative Site
state: District of Columbia
city: Jacksonville
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facility: Novartis Investigative Site
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facility: Novartis Investigative Site
state: Florida
city: Naples
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city: New Port Richey
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state: Florida
city: Orlando
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state: Florida
city: Ormond Beach
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facility: Novartis Investigative Site
state: Florida
city: Pompano Beach
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facility: Novartis Investigative Site
state: Florida
city: Ponte Vedra Beach
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facility: Novartis Investigative Site
state: Florida
city: Port Charlotte
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city: Sarasota
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city: Tallahassee
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city: Vero Beach
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city: West Palm Beach
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city: Atlanta
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state: Georgia
city: Elk Grove Village
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state: Illinois
city: Evanston
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state: Illinois
city: Flossmoor
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facility: Novartis Investigative Site
state: Illinois
city: Northbrook
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city: Indianapolis
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city: Indianapolis
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city: West Des Moines
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city: Kansas City
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city: Lenexa
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city: Louisville
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city: Hammond
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city: New Orleans
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city: Boston
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city: Springfield
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city: Detroit
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city: Farmington Hills
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city: Saint Louis
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city: Newark
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city: Chapel Hill
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city: Charlotte
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facility: Novartis Investigative Site
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city: Winston-Salem
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city: Cordova
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city: Knoxville
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city: Nashville
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city: Nashville
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city: Houston
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city: Round Rock
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city: Alexandria
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city: Charlottesville
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city: Richmond
country: United States
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city: Roanoke
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city: Issaquah
country: United States
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state: Washington
city: Seattle
country: United States
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city: Seattle
country: United States
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city: Milwaukee
country: United States
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state: Wisconsin
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos aires
country: Argentina
facility: Novartis Investigative Site
city: Belo Horizonte
country: Brazil
facility: Novartis Investigative Site
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: Rio Grande Do Sul
city: Joinville
country: Brazil
facility: Novartis Investigative Site
state: Santa Catarina
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Campina Grande do Sul
country: Brazil
facility: Novartis Investigative Site
city: Goiania
country: Brazil
facility: Novartis Investigative Site
city: Passo Fundo
country: Brazil
facility: Novartis Investigative Site
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Burnaby
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Halifax
country: Canada
facility: Novartis Investigative Site
state: Nova Scotia
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Chicoutimi
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Tlalnepantla
country: Mexico
facility: Novartis Investigative Site
state: Edo De Mexico
city: Monterrey
country: Mexico
facility: Novartis Investigative Site
state: Nuevo León
city: San Luis Potosi
country: Mexico
facility: Novartis Investigative Site
state: San Luis Potosí
city: Aguascalientes
country: Mexico
facility: Novartis Investigative Site
city: Chihuahua
country: Mexico
facility: Novartis Investigative Site
city: Chihuahua
country: Mexico
facility: Novartis Investigative Site
city: Monterrey
country: Mexico
facility: Novartis Investigative Site
city: Guaynabo
country: Puerto Rico
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.