NCT02342704

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).

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
111

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Nov 2014

Geographic Reach
9 countries

42 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 30, 2014

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

January 15, 2015

Completed
6 days until next milestone

First Posted

Study publicly available on registry

January 21, 2015

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 18, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 18, 2016

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

June 9, 2017

Completed
Last Updated

June 9, 2017

Status Verified

May 1, 2017

Enrollment Period

1.5 years

First QC Date

January 15, 2015

Results QC Date

May 17, 2017

Last Update Submit

May 17, 2017

Conditions

Outcome Measures

Primary Outcomes (1)

  • Cumulative Number of ≥ 6-Month Confirmed T1-Hypointense Lesions Arising From New On-Treatment T1-Gadolinium-Enhancing (Gd+) Lesions

    Up to Week 52

Secondary Outcomes (10)

  • Cumulative Number of New T1-Gd+ Lesions

    Baseline, Week 4, Week 12, Week 24

  • Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 24

    Baseline, Week 24

  • Change From Baseline in Total T1-Hypointense and Total T2-Hyperintense Lesion Volumes at Week 52

    Baseline, Week 52

  • Cumulative Number of New or Enlarging T2 Lesions

    Baseline, Week 24

  • Proportion of Participants With No Evidence of Disease Activity (NEDA)

    Up to Week 52

  • +5 more secondary outcomes

Study Arms (2)

natalizumab

EXPERIMENTAL

Open-label natalizumab 300 mg IV every 4 weeks (Q4W)

Drug: natalizumab

fingolimod

ACTIVE COMPARATOR

Open-label fingolimod 0.5 mg once daily orally

Drug: fingolimod

Interventions

Administered as specified in the treatment arm

Also known as: BG00002, Tysabri
natalizumab

Administered as specified in the treatment arm

Also known as: FTY720, Gilenya
fingolimod

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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.
  • 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.
  • +6 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (42)

Research Site

Aurora, Colorado, 80045, United States

Location

Research Site

Colorado Springs, Colorado, 80907, United States

Location

Research Site

Port Charlotte, Florida, 33952, United States

Location

Research Site

Atlanta, Georgia, 30327, United States

Location

Research Site

Des Moines, Iowa, 50314, United States

Location

Research Site

Philadelphia, Pennsylvania, 19104, United States

Location

Research Site

Knoxville, Tennessee, 37922, United States

Location

Research Site

Round Rock, Texas, 78681, United States

Location

Research Site

San Antonio, Texas, 78229, United States

Location

Research Site

Seattle, Washington, 98122, United States

Location

Research Site

Tacoma, Washington, 98405, United States

Location

Research Site

Milwaukee, Wisconsin, 53215, United States

Location

Research Site

Camperdown, New South Wales, 2050, Australia

Location

Research Site

New Lambton Heights, New South Wales, 2305, Australia

Location

Research Site

Heidelberg, Victoria, 3084, Australia

Location

Research Site

Brno, 625 00, Czechia

Location

Research Site

Brno, 656 91, Czechia

Location

Research Site

Hradec Králové, 500 05, Czechia

Location

Research Site

Jihlava, 58633, Czechia

Location

Research Site

Ostrava - Poruba, 708 52, Czechia

Location

Research Site

Pardubice, 532 03, Czechia

Location

Research Site

Prague, 150 06, Czechia

Location

Research Site

Teplice, 415 01, Czechia

Location

Research Site

Nîmes, Gard, 30029, France

Location

Research Site

Libourne, Gironde, 33505, France

Location

Research Site

Toulouse, Haute Garonne, 31059, France

Location

Research Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Research Site

Erbach im Odenwald, Hesse, 64711, Germany

Location

Research Site

Gianicolense, Roma, 87-00151, Italy

Location

Research Site

Roma, 00189, Italy

Location

Research Site

El Palmar, Murcia, 30120, Spain

Location

Research Site

Málaga, Málaga, 29010, Spain

Location

Research Site

Vigo, Pontevedra, 36204, Spain

Location

Research Site

Santa Cruz de Tenerife, Tenerife, 38010, Spain

Location

Research Site

Barcelona, 08035, Spain

Location

Research Site

Girona, 17007, Spain

Location

Research Site

Madrid, 28006, Spain

Location

Research Site

Seville, E 41009, Spain

Location

Research Site

Gothenburg, 41345, Sweden

Location

Research Site

Stockholm, 17176, Sweden

Location

Research Site

London, Greater London, SE5 9NU, United Kingdom

Location

Research Site

Glasgow, Strathclyde, G51 4TF, United Kingdom

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

NatalizumabFingolimod Hydrochloride

Condition Hierarchy (Ancestors)

Multiple SclerosisDemyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsSphingosineAmino AlcoholsAlcoholsOrganic ChemicalsPropylene GlycolsGlycolsAmines

Results Point of Contact

Title
Biogen Study Medical Director
Organization
Biogen

Study Officials

  • Medical Director

    Biogen

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 15, 2015

First Posted

January 21, 2015

Study Start

November 30, 2014

Primary Completion

May 18, 2016

Study Completion

May 18, 2016

Last Updated

June 9, 2017

Results First Posted

June 9, 2017

Record last verified: 2017-05

Locations