Clinical trial NCT02342704: Impact of Natalizumab Versus Fingolimod in Relapsing-Remitting Multiple Sclerosis (RRMS) Participants
Official title: A Multicenter, Randomized, Open-Label Study to Assess the Impact of Natalizumab Versus Fingolimod on Central Nervous System Tissue Damage and Recovery in Active Relapsing-Remitting Multiple Sclerosis Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Relapsing-Remitting Multiple Sclerosis
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2015-01-21
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to assess the effect of natalizumab compared to fingolimod on the evolution of new on-treatment T1-gadolinium-enhancing (Gd+) lesions to persistent black holes (PBH) over 52 weeks. The secondary objectives of this study in this study population are to assess the effect of natalizumab compared to fingolimod on: magnetic resonance imaging (MRI) measures of central nervous system (CNS) tissue destruction as measured by the number of new T1-Gd+ lesions; various other MRI measures of disease activity; No Evidence of Disease Activity (NEDA); Relapse on treatment over 52 weeks; The change in information processing speed as measured by the Symbol Digit Modalities Test (SDMT).

Detailed description: This study also includes a Diffusion Tensor Imaging (DTI) sub-study that includes healthy volunteers. Healthy volunteers will not receive any study medication.

Eligibility criteria: Key Inclusion Criteria for MS Patients:

* Must have a documented diagnosis of relapsing MS (McDonald 2010 Criteria) at study screening with EDSS score from 0.0 to 5.5.
* If the subject is on Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera, and Aubagio (BRACE-TA) at study screening:
* He/she must have been on therapy for at least 6 months (unless experiencing highly active disease), have at least 9 T2-hyperintense lesions on a brain MRI scan, and have experienced ≥1 relapse within the last 6 months prior to study screening with ≥1 new T1-Gd+ lesion on a brain MRI scan performed ≤6 months prior to study screening or ≥2 new T2 lesions on a brain MRI scan performed ≤6 months prior to study screening, with comparison made to a T2 MRI scan performed up to 18 months before study screening
* If the subject has highly active disease, regardless of whether they are disease-modifying therapy (DMT)-naïve or had previous exposure to Betaseron, Rebif, Avonex, Copaxone, Extavia, Tecfidera, and Aubagio (BRACE-TA), they must have had ≥2 disabling relapses in the 12 months prior to study screening and either ≥1 new T1-Gd+ lesion on a brain MRI scan performed ≤6 months prior to study screening or ≥2 new T2 lesions on a brain MRI scan performed ≤6 months prior to study screening, with comparison made to a T2 MRI scan performed up to 18 months before study screening

Key Exclusion Criteria for MS Patients:

* Diagnosis of Primary Progressive Multiple Sclerosis and/or Secondary Progressive Multiple Sclerosis.
* History or positive test result at study screening for human immunodeficiency virus (HIV), hepatitis C virus (HCV) antibody or current hepatitis B infection (defined as positive for hepatitis B surface antigen \[HBsAg\] and/or hepatitis B core antibody \[HBcAb\]).
* Prior treatment with natalizumab or fingolimod.
* History of or known active malignant disease, including solid tumors and hematologic malignancies (subjects with cutaneous basal and squamous cell carcinoma that has been completely excised and considered cured prior to study screening remain eligible).
* History of opportunistic infections or any clinically significant major disease, as determined by the Investigator.
* A clinically significant infectious illness (e.g., pneumonia, septicemia) within the 1 month prior to study screening.
* History of drug or alcohol abuse (as defined by the Investigator) within 1 year prior to study screening.
* Prior history of immunosuppressant use (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate, cladribine, rituximab), or exposure to intravenous immunoglobulin (IGIV), monoclonal antibodies, cytokines, growth factors, soluble receptors, other recombinant products, or fusion proteins in the last 12 months prior to study screening.
* History of myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure in last 6 months.
* Treatment with Class Ia (e.g., procainamide, quinidine, ajmaline, disopyramide) or Class III (amiodarone, bretylium, dofelitide, sotalol, ibulitide, azilimide) anti-arrhythmic drugs.
* Concurrent therapy with drugs that slow heart rate (e.g., beta-blockers, heart-rate lowering calcium channel blockers such as diltiazem or verapamil, or digoxin).
* Hypertension not controlled with prescribed medications.
* History of severe respiratory disease, pulmonary fibrosis or class III or IV chronic obstructive pulmonary disease.
* The use of live or live attenuated vaccination within 8 weeks of study screening.

Key Inclusion Criteria for Healthy Volunteers:

* Subjects who are generally healthy as demonstrated by physical examination and by medical history, with no history or evidence of major illnesses, diseases, or disorders.
* Subjects of childbearing potential must practice effective contraception and be willing and able to continue contraception for duration of the study.
* No history of drug or alcohol abuse (as defined by the Investigator) within 1 year prior to study screening.

Key Exclusion Criteria for Healthy Volunteers:

* Claustrophobia sufficient to interfere with generating reliable MRI scans.
* History of other major illness including neurological disorders as determined by the Investigator.
* Presence of a metal device affected by MRI (e.g., any type of electronic, mechanical or magnetic implant, cardiac pacemaker, aneurysm clips, implanted cardiac defibrillator) or potential ferromagnetic foreign body (metal slivers, metal shavings, other metal objects), which would be a contraindication for MRI.
* Women who are currently pregnant or breastfeeding, or who have a positive pregnancy test result at screening.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Primary outcomes:
measure: Cumulative Number of ≥ 6-Month Confirmed T1-Hypointense Lesions Arising From New On-Treatment T1-Gadolinium-Enhancing (Gd+) Lesions
timeFrame: Up to Week 52
Secondary outcomes:
measure: Cumulative Number of New T1-Gd+ Lesions
timeFrame: Baseline, Week 4, Week 12, Week 24
measure: Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 52
timeFrame: Baseline, Week 52
measure: Cumulative Number of New or Enlarging T2 Lesions
timeFrame: Baseline, Week 24
measure: Proportion of Participants With No Evidence of Disease Activity (NEDA)
timeFrame: Up to Week 52
measure: Time to First Relapse
timeFrame: Up to Week 52
measure: Cumulative Risk of Relapse
timeFrame: Up to Week 52
measure: Time to Complete Recovery From First Relapse
timeFrame: Up to Week 52
measure: Change From Baseline in Symbol Digit Modalities Test (SDMT) at Week 24
timeFrame: Baseline, Week 24
measure: Change From Baseline in SDMT at Week 52
timeFrame: Baseline, Week 52
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Colorado Springs
country: United States
facility: Research Site
state: Colorado
city: Port Charlotte
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Des Moines
country: United States
facility: Research Site
state: Iowa
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Round Rock
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Tacoma
country: United States
facility: Research Site
state: Washington
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Camperdown
country: Australia
facility: Research Site
state: New South Wales
city: New Lambton Heights
country: Australia
facility: Research Site
state: New South Wales
city: Heidelberg
country: Australia
facility: Research Site
state: Victoria
city: Brno
country: Czechia
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Hradec Kralove
country: Czechia
facility: Research Site
city: Jihlava
country: Czechia
facility: Research Site
city: Ostrava - Poruba
country: Czechia
facility: Research Site
city: Pardubice
country: Czechia
facility: Research Site
city: Praha 5
country: Czechia
facility: Research Site
city: Teplice
country: Czechia
facility: Research Site
city: Nimes
country: France
facility: Research Site
state: Gard
city: Libourne Cedex
country: France
facility: Research Site
state: Gironde
city: Toulouse cedex 9
country: France
facility: Research Site
state: Haute Garonne
city: Freiburg
country: Germany
facility: Research Site
state: Baden Wuerttemberg
city: Erbach
country: Germany
facility: Research Site
state: Hessen
city: Gianicolense
country: Italy
facility: Research Site
state: Roma
city: Roma
country: Italy
facility: Research Site
city: El Palmar
country: Spain
facility: Research Site
state: Murcia
city: Malaga
country: Spain
facility: Research Site
state: Málaga
city: Vigo
country: Spain
facility: Research Site
state: Pontevedra
city: Santa Cruz de Tenerife
country: Spain
facility: Research Site
state: Tenerife
city: Barcelona
country: Spain
facility: Research Site
city: Girona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Göteborg
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
state: Greater London
city: Glasgow
country: United Kingdom
facility: Research Site
state: Strathclyde
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Butzkueven H, Licata S, Jeffery D, Arnold DL, Filippi M, Geurts JJ, Santra S, Campbell N, Ho PR; REVEAL Investigators. Natalizumab versus fingolimod for patients with active relapsing-remitting multiple sclerosis: results from REVEAL, a prospective, randomised head-to-head study. BMJ Open. 2020 Oct 20;10(10):e038861. doi: 10.1136/bmjopen-2020-038861.