A Study to Evaluate Efficacy, Safety, and Tolerability of EID of Natalizumab (BG00002) in Participants With RRMS Switching From Treatment With Natalizumab SID in Relation to Continued SID Treatment- Followed by Extension Study Comprising SC and IV Natalizumab Administration

A Randomized, Controlled, Open-Label, Rater-Blinded, Phase 3b Study of the Efficacy, Safety, and Tolerability of 6-Week Extended Interval Dosing (EID) of Natalizumab (BG00002) in Subjects With Relapsing-Remitting Multiple Sclerosis Switching From Treatment With 4-Week Natalizumab Standard Interval Dosing (SID) in Relation to Continued SID Treatment - Followed by an Open-Label Crossover Extension Study Comprising Subcutaneous and Intravenous Natalizumab Administration

Part 1: The primary objective is to evaluate the efficacy of natalizumab extended interval dosing (EID) (every 6 weeks [Q6W]) in participants who have previously been treated with natalizumab standard interval dosing (SID) (every 4 weeks [Q4W]) for at least 12 months, in relation to continued Q4W treatment. The secondary objectives is to evaluate relapse-based clinical efficacy measures, disability worsening, additional Magnetic resonance imaging (MRI)-lesion efficacy measures and safety of Q6W in participants who have previously been treated with natalizumab Q4W for at least 12 months, in relation to continued Q4W treatment.

Part 2: The primary objective is to evaluate participant preference for subcutaneous (SC) versus intravenous (IV) route of natalizumab administration. The secondary objectives is to evaluate treatment satisfaction, drug preparation and administration time, safety and immunogenicity, efficacy and characterize pharmacokinetic (PK) and pharmacodynamic (PD) drug preparation and administration time of SC versus IV routes of natalizumab administration.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Drug: Natalizumab; Drug: Natalizumab

Detailed Description

This study will be conducted in 2 parts. At the end of part 1, participants who provide consent and are eligible, and newly enrolled participants, will enter part 2, an Open Label Extension comprising a crossover analysis.

Those participants who completed part 1 and cannot participate, or elect not to participate, in Part 2 (Open label extension) will enter a 12-week follow-up.

• Study Type: Interventional
• Enrollment (Actual): 585
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Sydney, New South Wales, Australia, 2050
      • Brain and Mind Centre
  • South Australia
    • Elizabeth Vale, South Australia, Australia, 5112
      • Lyell McEwin Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint-luc
  • Bruxelles, Belgium, 1070
    • Cliniques universitaires de Bruxelles Hopital Erasme
  • Edegem, Belgium, 2650
    • UZA
  • La Louvière, Belgium, 7100
    • CHU de Tivoli
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
  • Quebec
    • Gatineau, Quebec, Canada, J8Y 1W2
      • Clinique Neuro-Outaouais
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Recherche SEPMUS
    • Montreal, Quebec, Canada, H2X 0A9
      • CHUM Centre de Recherche
    • Montreal, Quebec, Canada, H3A 3B4
      • Montreal Neurological Institute Clinical Research Unit
• France
  • Bordeaux, France, 33076
    • Groupe Hospitalier Pellegrin - Hôpital Pellegrin
  • Caen, France, 14033
    • Chu Caen - Hôpital de La Côte de Nacre
  • Lille, France, 59037
    • Hopital Roger Salengro - CHU Lille
  • Nice, France, 6001
    • CHU Nice - Hôpital Pasteur
  • Saint Herblain, France, 44800
    • CHU Nantes - Hopital Nord Laënnec
  • Strasbourg, France, 67091
    • CHU Strasbourg - Nouvel Hopital Civil
• Germany
  • Bamberg, Germany, 96052
    • Neurologie im Alphamed
  • Berlin, Germany, 10117
    • Charité - Campus Charité Mitte
  • Bochum, Germany, 44791
    • Katholisches Klinikum Bochum gGmbH
  • Erbach, Germany, 64711
    • Neuro Centrum Science GmbH
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen
  • Freiburg, Germany, 79106
    • Universitaetsklinikum Freiburg
  • Marburg, Germany, 35043
    • Universitaetsklinikum Giessen und Marburg GmbH Standort Marburg
  • Muenster, Germany, 48149
    • Universitaetsklinikum Muenster
  • Munich, Germany, 81675
    • Klinikum rechts der Isar der TU Muenchen
  • Stuttgart, Germany, 70182
    • Synconcept GmbH - Neuro MVZ
• Israel
  • Ramat Gan, Israel, 52363
    • Chaim Sheba Medical Center
• Italy
  • Catania, Italy, 95123
    • Azienda Ospedaliero Universitaria Policlinico "Gaspare Rodolico - San Marco" (Presidio G. Rodolico)
  • Cefalù, Italy, 90015
    • Fondazione Istituto G.Giglio di Cefalù
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Neurologico Carlo Besta
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria- Università Degli Studi Della Campania "Luigi Vanvitelli"
  • Pozzilli, Italy, 86077
    • I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo
• Netherlands
  • Breda, Netherlands, 4818 CK
    • Amphia Ziekenhuis, Molengracht
  • Nieuwegein, Netherlands, 3435 CM
    • St. Antonius ziekenhuis
  • Sittard, Netherlands, 6162 BG
    • Zuyderland Medisch Centrum - Sittard-Geleen
• Spain
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Malaga, Spain, 29010
    • Hospital Regional Universitario de Malaga
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Catalonia
    • Lleida, Catalonia, Spain, 25198
      • Hospital Universitari Arnau de Vilanova
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Hospital Universitario Virgen de La Arrixaca
• United Kingdom
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital
  • Nottingham, United Kingdom, NG7 2UH
    • Nottingham University Hospital, Queen's Medical Centre
  • Salford, United Kingdom, M6 8HD
    • Salford Care Organisation
  • Sheffield, United Kingdom, S10 2JF
    • Royal Hallamshire Hospital
  • Swansea, United Kingdom, SA6 6NL
    • Morriston Hospital
  • Greater London
    • London, Greater London, United Kingdom, SE5 9RS
      • King's College Hospital
    • London, Greater London, United Kingdom, WC1N 3BG
      • The National Hospital for Neurology & Neurosurgery
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L9 7LJ
      • Walton Centre for Neurology & Neurosurgery.
  • Strathclyde
    • Glasgow, Strathclyde, United Kingdom, G51 4TF
      • Queen Elizabeth University Hospital Campus
  • Tyne & Wear
    • Newcastle upon Tyne, Tyne & Wear, United Kingdom, NE4 5PL
      • Newcastle University- Clinical Ageing Research Unit
• United States
  • Alabama
    • Cullman, Alabama, United States, 35058
      • North Central Neurology Associates, P.C.
    • Homewood, Alabama, United States, 35209
      • Alabama Neurology Associates
  • California
    • Irvine, California, United States, 92607
      • UCI MIND
    • La Jolla, California, United States, 92037
      • UC San Diego Movement Disorder Center
    • Laguna Hills, California, United States, 92653
      • MS Center of California
    • Palo Alto, California, United States, 94304
      • Stanford Hospital and Clinics
  • Colorado
    • Aurora, Colorado, United States, 80010-0510
      • University of Colorado Hospital Anschutz Outpatient Pavillion
    • Fort Collins, Colorado, United States, 80528
      • Advanced Neurosciences Research
  • Connecticut
    • Fairfield, Connecticut, United States, 06824
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20007-2113
      • Georgetown University Hospital-Medstar
  • Florida
    • Miami, Florida, United States, 33125
      • University of Miami Miller School of Medicine
    • Sunrise, Florida, United States, 33351
      • Infinity Clinical Research, LLC
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30327
      • Atlanta NeuroScience Institute
    • Atlanta, Georgia, United States, 30309
      • Shepherd Center, Inc.
  • Illinois
    • Evanston, Illinois, United States, 60208
      • Northwestern University
    • Evanston, Illinois, United States, 60201
      • Northshore University Healthsystem
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • College Park Family Care Center
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic Inc. - PARENT ACCOUNT
    • Foxboro, Massachusetts, United States, 02035
      • Neurology Center of New England P.C.
    • Jamaica Plain, Massachusetts, United States, 02130-2075
      • Beth Israel Deaconess Medical Center, Inc.
    • Wellesley, Massachusetts, United States, 02481
      • Dragonfly Research, LLC
    • Weymouth, Massachusetts, United States, 02190
      • South Shore Neurology Associates
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Michigan Institute for Neurological Disorders
    • Grand Rapids, Michigan, United States, 49506
      • Michigan State University
    • Owosso, Michigan, United States, 48867
      • Memorial Healthcare
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • Minneapolis Clinic of Neurology
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University, School of Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo Center for Brain Health
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • RWJ Barnabas Health
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • New York, New York, United States, 10032
      • Columbia University Hervert Irving Comprehensive Cancer Center
    • New York, New York, United States, 10016
      • NYU Langone Clinical Cancer Center
    • Plainview, New York, United States, 11803
      • Island Neurological Associates, P.C.
  • North Carolina
    • Raleigh, North Carolina, United States, 27607-6010
      • Raleigh Neurology Associates
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43214
      • OhioHealth Riverside Methodist Hospital
    • Dayton, Ohio, United States, 45459
      • Dayton Center for Neurological Disorders
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence Neurological Specialties
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee-Womens Hospital of UPMC
  • Tennessee
    • Knoxville, Tennessee, United States, 37922
      • Sibyl Wray, MD Neurology, PC
    • Nashville, Tennessee, United States, 37215
      • Vanderbilt University Medical Center
  • Texas
    • Round Rock, Texas, United States, 78681
      • Central Texas Neurology Consultants
  • Utah
    • Salt Lake City, Utah, United States, 84103
      • Rocky Mountain MS Research Group LLC
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Vienna, Virginia, United States, 22182
      • Multiple Sclerosis Center of Greater Washington
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53227
      • Wheaton Franciscan Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

For Part 1:

• Ability of the participant to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations.
• Diagnosis of relapsing remitting multiple sclerosis (RRMS) according to the McDonald criteria [Thompson 2018].
• Treatment with natalizumab as disease-modifying monotherapy for RRMS that is consistent with the approved dosing for a minimum of 12 months prior to randomization. The participant must have received at least 11 doses of natalizumab in the 12 months prior to randomization with no missed doses in the 3 months prior to randomization.
• Expanded Disability Status Scale (EDSS) score <=5.5 at screening.
• No relapses in the last 12 months prior to randomization, as determined by the enrolling Investigator.

For Part 2:

• Ability of the participants to understand the purpose and risks of the study and provide signed and dated informed consent for Part 2 and authorization to use confidential health information in accordance with national and local participant privacy regulations.
• Completed Part 1 Week 72 visit while remaining on their randomized treatment assignment of Q4W or Q6W.

Key Exclusion Criteria:

For Part 1:

• Primary and secondary progressive multiple sclerosis (MS).
• MRI positive for Gd-enhancing lesions at screening.
• Participants for whom MRI is contraindicated (e.g., have a contraindicated pacemaker or other contraindicated implanted metal device, have suffered, or are at risk for, side effects from Gd, or have claustrophobia that cannot be medically managed).
• History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic (including diabetes), urologic, pulmonary, neurologic (except for RRMS), dermatologic, psychiatric, renal, or other major disease that would preclude participation in a clinical study, in the opinion of the Investigator.
• Presence of anti-natalizumab antibodies at screening.

For Part 2:

• Participants treated with natalizumab Q6W was reverted to natalizumab Q4W by choice or as rescue treatment in Part 1.
• Participant received treatment with any MS disease-modifying therapy other than natalizumab in Part 1 or in the period between Part 1 and Part 2.
• History of human immunodeficiency virus or history of other immunodeficient conditions.
• Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 30 days (or 5 half-lives of the agent, whichever is longer) prior to the Baseline Visit or at any time during this study.
• Inability to comply with study requirements.
• Other unspecified reasons that, in the opinion of the Investigator or Biogen, make the participant unsuitable for enrollment.

The inclusion and exclusion criteria for new participants who did not participate in Part 1 of the study are the same as those for participants who did participate in Part 1.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: IV Q4W; Participants received natalizumab 300 mg intravenous (IV) infusion once Q4W up to Week 72.	Drug: Natalizumab; Natalizumab 300 mg SC injection or IV infusion.; Other Names: BG00002; Drug: Natalizumab; Natalizumab 300 mg IV infusion.; Other Names: BG00002
Experimental: Part 1: IV Q6W; Participants received natalizumab 300 mg IV infusion once Q6W up to Week 72.	Drug: Natalizumab; Natalizumab 300 mg SC injection or IV infusion.; Other Names: BG00002; Drug: Natalizumab; Natalizumab 300 mg IV infusion.; Other Names: BG00002
Experimental: Part 2: Run-in Period: IV Q6W; Participants who completed Part 1 or were newly enrolled in Part 2 received natalizumab 300 mg IV infusion Q6W from Week 72 through Week 102.	Drug: Natalizumab; Natalizumab 300 mg SC injection or IV infusion.; Other Names: BG00002; Drug: Natalizumab; Natalizumab 300 mg IV infusion.; Other Names: BG00002
Experimental: Part 2: Crossover Period: IV Q6W, then SC Q6W; Participants who completed run-in period of Part 2 were randomized to receive natalizumab 300 mg IV infusion Q6W from Week 108 through Week 126 followed by natalizumab 300 mg subcutaneous (SC) injection Q6W from Week 132 through Week 150 along with a single dose of natalizumab 300 mg SC injection or IV infusion as per participant's choice at Week 156.	Drug: Natalizumab; Natalizumab 300 mg SC injection or IV infusion.; Other Names: BG00002; Drug: Natalizumab; Natalizumab 300 mg IV infusion.; Other Names: BG00002
Experimental: Part 2: Crossover Period: SC Q6W, then IV Q6W; Participants who completed run-in period of Part 2 were randomized to receive natalizumab 300 mg SC injection Q6W from Week 108 through Week 126 followed by natalizumab 300 mg IV infusion Q6W from Week 132 through Week 150 along with a single dose of natalizumab 300 mg SC injection or IV infusion as per participant's choice at Week 156.	Drug: Natalizumab; Natalizumab 300 mg SC injection or IV infusion.; Other Names: BG00002; Drug: Natalizumab; Natalizumab 300 mg IV infusion.; Other Names: BG00002

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions at Week 72	T2 hyperintense lesions were analyzed by magnetic resonance imaging (MRI) scans of brain. New MRI scans were compared with the prior MRI scans to analyze the number of new or newly enlarging T2 hyperintense lesions at Week 72 relative to baseline.	Week 72
Part 2: Percentage of Participants Indicating a Preference for Natalizumab SC Administration at the End of Crossover Period of Part 2		Week 150

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Time to First Relapse as Adjudicated by an Independent Neurology Evaluation Committee (INEC)	Relapse is defined as the onset of new or recurrent neurological symptoms, not associated with fever, infection, severe stress, or drug toxicity, lasting at least 24 hours, accompanied by new objective abnormalities on a neurological examination. Only relapses confirmed by an INEC were included in the analysis. Time to First Relapse was estimated by Kaplan-Meier method.	Up to Week 72
Part 1: Annualized Relapse Rate at Week 72	Annualized relapse rate is calculated as the total number of INEC-confirmed relapses that occurred during the treatment period divided by the total number of participant-years followed in the period.	Week 72
Part 1: Time to Expanded Disability Status Scale (EDSS) Worsening	Confirmed EDSS worsening is defined as an increase of at least 1.0 point from a baseline EDSS score ≥ 1.0 or an increase of at least 1.5 points from a baseline EDSS score of 0 that is confirmed after at least 24 weeks. Time to EDSS worsening is estimated by Kaplan-Meier method.	Up to Week 72
Part 1: Mean Number of New T1 Hypointense Lesions at Weeks 24, 48, and 72	T1 hypointense lesions on brain were analyzed by MRI scans of brain. New MRI scans were compared with the prior MRI scans to analyze the number of new T1 hypointense lesions at Weeks 24, 48, and 72 relative to baseline.	Weeks 24, 48, and 72
Part 1: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions at Weeks 24 and 48	T2 hyperintense lesions were analyzed by MRI scans of brain. New MRI scans were compared with the prior MRI scans to analyze the number of new or newly enlarging T2 hyperintense lesions at Weeks 24 and 48 relative to baseline.	Weeks 24 and 48
Part 1: Mean Number of New Gadolinium (Gd) Enhancing Lesions at Weeks 24, 48, and 72	Gd enhancing lesions on brain were analyzed by MRI scans of brain. New MRI scans were compared with the prior MRI scans to analyze the number of new Gd enhancing lesions at Weeks 24, 48, and 72 relative to baseline.	Weeks 24, 48, and 72
Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is any event occurring on or after first dose after randomization up to 12 weeks (or 24 weeks for PML [progressive multifocal leukoencephalopathy] events) following the last dose on the study.An SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, is a medically important event.	Baseline up to Week 84
Part 2: Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Scores During the Crossover Period	The TSQM has 14 questions that assesses participants' global satisfaction level with their treatment in 4 domains: side effects (There are 5 questions in the side effects domain, however one of them is a Yes/No question and there are 4 sub-components, hence a maximum score of 20), effectiveness (3 questions), global satisfaction (3 questions), and convenience (3 questions). All questions are scored from 1 (least satisfied) to 5 or 7 (most satisfied). The total score is summed for each domain to obtain: side effects (1-20), effectiveness (1-21), global satisfaction (1-17), and convenience (1-21), using transformed scores between 0 and 100 for effectiveness. Lower total scores in each domain indicate dissatisfaction with the study medication and higher total scores indicate satisfaction.	Part 2 Baseline (Week 108) up to Week 156
Part 2: Mean Time for Drug Preparation and Drug Administration During the Crossover Period		Week 108 up to Week 156
Part 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is any event occurring on or after first dose after randomization up to and including 12 weeks (or 24 weeks for PML events) following the last dose on the study.	Part 2: Baseline (Week 108) up to Week 180
Part 2: Percentage of Participants With Anti-Natalizumab Antibodies During the Crossover Period		Part 2 Baseline (Week 108) up to Week 156
Part 2: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions During the Crossover Period	T2 hyperintense lesions were analyzed by MRI scans of brain. New MRI scans were compared with the prior MRI scans to analyze the number of new or newly enlarging T2 hyperintense lesions during the crossover period of Part 2 relative to baseline.	Part 2 Baseline (Week 108) up to Week 156
Part 2: Time to First Relapse During the Crossover Period	Relapse is defined as the onset of new or recurrent neurological symptoms, not associated with fever, infection, severe stress, or drug toxicity, lasting at least 24 hours. The time to first relapse is defined as the time from the first randomized dose in Part 2 up to the first relapse. Time to First Relapse is estimated by Kaplan-Meier method.	Part 2 Baseline (Week 108) up to Week 156
Part 2: Annualized Relapse Rate During the Crossover Period	Annualized relapse rate is calculated as the total number of relapses that occurred during the treatment period divided by the total number of participant-years followed in the period.	Part 2 Baseline (Week 108) up to Week 156
Part 2: Change From Baseline in EDSS Score During the Crossover Period	The EDSS is a scale based on standardized neurological examination which comprised of optic, brain stem, pyramidal, cerebellar, sensory and cerebral functions, as well as walking ability. It measures the MS disability status on a scale ranging from 0 (normal) to 10 (death due to MS), with higher scores indicating more disability.	Part 2 Baseline (Week 108) up to Week 156
Part 2: Mean Number of New Gd Enhancing Lesions During the Crossover Period	Gd enhancing lesions on brain were analyzed by MRI scans of brain. New MRI scans were compared with the prior MRI scans to analyze the number of new Gd enhancing lesions during the crossover period of Part 2 relative to baseline.	Week 108 up to Week 156
Part 2: Mean Number of New T1 Hypointense Lesions During the Crossover Period	T1 hypointense lesions on brain were analyzed by MRI scans of brain. New MRI scans were compared with the prior MRI scans to analyze the number of new T1 hypointense lesions during the crossover period of Part 2 relative to baseline.	Week 108 up to Week 156
Part 2: Mean Percentage Change From Baseline in Brain Volume During the Crossover Period		Part 2 Baseline (Week 108) up to Week 156
Part 2: Change From Baseline in Cortical and Thalamic Brain Region Volume During the Crossover Period		Part 2 Baseline (Week 108) up to Week 156
Part 2: Trough Serum Concentration of Natalizumab (Ctrough) During the Crossover Period		Pre-dose at Weeks 108, 114, 120, 126, 132, 138, 144, 150, and 156
Part 2: Mean Trough α4 Integrin Saturation During the Crossover Period		Pre-dose at Weeks 108, 114, 120, 126, 132, 138, 144, 150, and 156

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Medical Director, Biogen

Publications and helpful links

General Publications

• Foley JF, Defer G, Ryerson LZ, Cohen JA, Arnold DL, Butzkueven H, Cutter G, Giovannoni G, Killestein J, Wiendl H, Smirnakis K, Xiao S, Kong G, Kuhelj R, Campbell N; NOVA study investigators. Comparison of switching to 6-week dosing of natalizumab versus continuing with 4-week dosing in patients with relapsing-remitting multiple sclerosis (NOVA): a randomised, controlled, open-label, phase 3b trial. Lancet Neurol. 2022 Jul;21(7):608-619. doi: 10.1016/S1474-4422(22)00143-0. Epub 2022 Apr 25.

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2018
• Primary Completion (Actual): January 31, 2023
• Study Completion (Actual): July 24, 2023

Study Registration Dates

• First Submitted: September 27, 2018
• First Submitted That Met QC Criteria: September 27, 2018
• First Posted (Actual): October 1, 2018

Study Record Updates

• Last Update Posted (Actual): June 12, 2024
• Last Update Submitted That Met QC Criteria: May 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Immunologic Factors; Natalizumab
• Other Study ID Numbers: 101MS329; 2018-002145-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Please refer data queries to DataSharing@biogen.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No