Impact of Natalizumab Versus Fingolimod in Relapsing-Remitting Multiple Sclerosis (RRMS) Participants

Relapsing-Remitting Multiple Sclerosis Clinical Trial

— REVEAL  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02342704
• Other study ID #: 101MS408
• Secondary ID: 2013-004622-29
• Status: Terminated
• Phase: Phase 4
• First received: January 15, 2015
• Last updated: June 16, 2016
• Start date: November 2014
• Est. completion date: May 2016

Study information

• Verified date: June 2016
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos SanitariosAustralia: Department of Health and Ageing Therapeutic Goods AdministrationItaly: The Italian Medicines AgencyCzech Republic: State Institute for Drug ControlSweden: Medical Products AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyFrance: Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM)Germany: Paul-Ehrlich-InstitutUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Description:

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 129
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing-Remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• natalizumab
Administered as specified in the treatment arm
• fingolimod
Administered as specified in the treatment arm

Locations

Country	Name	City	State
Australia	Research Site	Camperdown	New South Wales
Australia	Research Site	Heidelberg	Victoria
Australia	Research Site	New Lambton Heights	New South Wales
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Hradec Kralove
Czech Republic	Research Site	Jihlava
Czech Republic	Research Site	Ostrava - Poruba
Czech Republic	Research Site	Pardubice
Czech Republic	Research Site	Praha 5
Czech Republic	Research Site	Teplice
France	Research Site	Libourne Cedex	Gironde
France	Research Site	Nimes	Gard
France	Research Site	Toulouse cedex 9	Haute Garonne
Germany	Research Site	Erbach	Hessen
Germany	Research Site	Freiburg	Baden Wuerttemberg
Italy	Research Site	Gianicolense	Roma
Italy	Research Site	Roma
Spain	Research Site	Barcelona
Spain	Research Site	El Palmar	Murcia
Spain	Research Site	Girona
Spain	Research Site	Madrid
Spain	Research Site	Malaga	Málaga
Spain	Research Site	Santa Cruz de Tenerife	Tenerife
Spain	Research Site	Sevilla
Spain	Research Site	Vigo	Pontevedra
Sweden	Research Site	Göteborg
Sweden	Research Site	Stockholm
United Kingdom	Research Site	Glasgow	Strathclyde
United Kingdom	Research Site	London	Greater London
United States	Research Site	Atlanta	Georgia
United States	Research Site	Aurora	Colorado
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Des Moines	Iowa
United States	Research Site	Knoxville	Tennessee
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Port Charlotte	Florida
United States	Research Site	Round Rock	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	Seattle	Washington
United States	Research Site	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Australia,  Czech Republic,  France,  Germany,  Italy,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cumulative number of =6-month confirmed T1-hypointense lesions arising from new on-treatment T1-Gd+ lesions		Up to Week 52	No
Secondary	Cumulative number of new T1-Gd+ lesions		Up to Week 52	No
Secondary	Change in total T1-hypointense and total T2-hyperintense lesion volumes		Up to Week 52	No
Secondary	Cumulative number of new or enlarging T2 lesions		Up to Week 52	No
Secondary	Proportion of participants with NEDA	No Evidence of Disease Activity is defined as: No relapses; No 12-week confirmed disability progression based on Expanded Disability Status Scale (EDSS) (defined as an increase of 1.0 or more on the EDSS from baseline of 1.0 or more, or an increase of 1.5 or more from a baseline score of 0) that was sustained for 12 weeks; No new T1-Gd+ lesions on brain MRI. No new or enlarging T2-hyperintense lesions.	Up to Week 52	No
Secondary	Time to first relapse	A clinical relapse is defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement.	Up to Week 52	No
Secondary	Cumulative risk of relapse		Up to Week 52	No
Secondary	Time to complete recovery from first relapse	12-week confirmed complete EDSS recovery from first on-treatment relapse is defined as an EDSS score that is equal to or lower than the last pre-relapse EDSS score and sustained for at least 12 weeks.	Up to Week 52	No
Secondary	Change in information processing speed as measured by SDMT	The SDMT examines sustained attention and concentration by primarily assessing complex visual scanning and tracking. The participant examines a series of 9 meaningless geometric symbols, which are labeled 1 to 9. For 90 seconds, the participant substitutes symbols in a row by the corresponding numbers and responds verbally. The score is the number of correct answers in 90 seconds.	Up to Week 52	No