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
2 other identifiers
interventional
585
11 countries
107
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Nov 2018
Longer than P75 for phase_3
107 active sites
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
First Submitted
Initial submission to the registry
September 27, 2018
CompletedFirst Posted
Study publicly available on registry
October 1, 2018
CompletedStudy Start
First participant enrolled
November 27, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
July 24, 2023
CompletedResults Posted
Study results publicly available
June 12, 2024
CompletedJune 12, 2024
May 1, 2024
4.2 years
September 27, 2018
January 31, 2024
May 14, 2024
Conditions
Outcome Measures
Primary Outcomes (2)
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 Outcomes (21)
Part 1: Time to First Relapse as Adjudicated by an Independent Neurology Evaluation Committee (INEC)
Up to Week 72
Part 1: Annualized Relapse Rate at Week 72
Week 72
Part 1: Time to Expanded Disability Status Scale (EDSS) Worsening
Up to Week 72
Part 1: Mean Number of New T1 Hypointense Lesions at Weeks 24, 48, and 72
Weeks 24, 48, and 72
Part 1: Mean Number of New or Newly Enlarging T2 Hyperintense Lesions at Weeks 24 and 48
Weeks 24 and 48
- +16 more secondary outcomes
Study Arms (5)
Part 1: IV Q4W
EXPERIMENTALParticipants received natalizumab 300 mg intravenous (IV) infusion once Q4W up to Week 72.
Part 1: IV Q6W
EXPERIMENTALParticipants received natalizumab 300 mg IV infusion once Q6W up to Week 72.
Part 2: Run-in Period: IV Q6W
EXPERIMENTALParticipants who completed Part 1 or were newly enrolled in Part 2 received natalizumab 300 mg IV infusion Q6W from Week 72 through Week 102.
Part 2: Crossover Period: IV Q6W, then SC Q6W
EXPERIMENTALParticipants 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.
Part 2: Crossover Period: SC Q6W, then IV Q6W
EXPERIMENTALParticipants 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.
Interventions
Natalizumab 300 mg IV infusion.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Biogenlead
Study Sites (107)
North Central Neurology Associates, P.C.
Cullman, Alabama, 35058, United States
Alabama Neurology Associates
Homewood, Alabama, 35209, United States
UCI MIND
Irvine, California, 92607, United States
UC San Diego Movement Disorder Center
La Jolla, California, 92037, United States
MS Center of California
Laguna Hills, California, 92653, United States
Stanford Hospital and Clinics
Palo Alto, California, 94304, United States
University of Colorado Hospital Anschutz Outpatient Pavillion
Aurora, Colorado, 80010-0510, United States
Advanced Neurosciences Research
Fort Collins, Colorado, 80528, United States
Yale University
Fairfield, Connecticut, 06824, United States
Georgetown University Hospital-Medstar
Washington D.C., District of Columbia, 20007-2113, United States
University of Miami Miller School of Medicine
Miami, Florida, 33125, United States
Infinity Clinical Research, LLC
Sunrise, Florida, 33351, United States
University of South Florida
Tampa, Florida, 33612, United States
Shepherd Center, Inc.
Atlanta, Georgia, 30309, United States
Atlanta Neuroscience Institute
Atlanta, Georgia, 30327, United States
NorthShore University HealthSystem
Evanston, Illinois, 60201, United States
Northwestern University
Evanston, Illinois, 60208, United States
College Park Family Care Center
Overland Park, Kansas, 66212, United States
Lahey Clinic Inc. - PARENT ACCOUNT
Burlington, Massachusetts, 01805, United States
Neurology Center of New England P.C.
Foxborough, Massachusetts, 02035, United States
Beth Israel Deaconess Medical Center, Inc.
Jamaica Plain, Massachusetts, 02130-2075, United States
Dragonfly Research, LLC
Wellesley, Massachusetts, 02481, United States
South Shore Neurology Associates
Weymouth, Massachusetts, 02190, United States
Michigan Institute for Neurological Disorders
Farmington Hills, Michigan, 48334, United States
Michigan State University
Grand Rapids, Michigan, 49506, United States
Memorial Healthcare
Owosso, Michigan, 48867, United States
Minneapolis Clinic of Neurology
Golden Valley, Minnesota, 55422, United States
Washington University, School of Medicine
St Louis, Missouri, 63110, United States
Cleveland Clinic Lou Ruvo Center for Brain Health
Las Vegas, Nevada, 89106, United States
RWJ Barnabas Health
Newark, New Jersey, 07102, United States
Holy Name Medical Center
Teaneck, New Jersey, 07666, United States
NYU Langone Clinical Cancer Center
New York, New York, 10016, United States
Mount Sinai Medical Center
New York, New York, 10029, United States
Columbia University Hervert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Island Neurological Associates, P.C.
Plainview, New York, 11803, United States
Raleigh Neurology Associates
Raleigh, North Carolina, 27607-6010, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
University of Cincinnati
Cincinnati, Ohio, 45267, United States
The Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
OhioHealth Riverside Methodist Hospital
Columbus, Ohio, 43214, United States
Dayton Center for Neurological Disorders
Dayton, Ohio, 45459, United States
Providence Neurological Specialties
Portland, Oregon, 97225, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, 15213, United States
Sibyl Wray, MD Neurology, PC
Knoxville, Tennessee, 37922, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37215, United States
Central Texas Neurology Consultants
Round Rock, Texas, 78681, United States
Rocky Mountain MS Research Group LLC
Salt Lake City, Utah, 84103, United States
University Of Virginia
Charlottesville, Virginia, 22908, United States
Multiple Sclerosis Center of Greater Washington
Vienna, Virginia, 22182, United States
Virginia Mason Medical Center
Seattle, Washington, 98101, United States
Wheaton Franciscan Healthcare
Milwaukee, Wisconsin, 53227, United States
Royal North Shore Hospital
St Leonards, New South Wales, 2065, Australia
Brain and Mind Centre
Sydney, New South Wales, 2050, Australia
Lyell McEwin Hospital
Elizabeth Vale, South Australia, 5112, Australia
Box Hill Hospital
Box Hill, Victoria, 3128, Australia
The Alfred Hospital
Melbourne, Victoria, 3004, Australia
Royal Melbourne Hospital
Parkville, Victoria, 3050, Australia
Cliniques Universitaires de Bruxelles Hopital Erasme
Brussels, 1070, Belgium
Cliniques Universitaires Saint-Luc
Brussels, 1200, Belgium
UZA
Edegem, 2650, Belgium
CHU de Tivoli
La Louvière, 7100, Belgium
St. Michael's Hospital
Toronto, Ontario, M5B 1W8, Canada
Clinique Neuro-Outaouais
Gatineau, Quebec, J8Y 1W2, Canada
Recherche SEPMUS
Greenfield Park, Quebec, J4V 2J2, Canada
CHUM Centre de Recherche
Montreal, Quebec, H2X 0A9, Canada
Montreal Neurological Institute Clinical Research Unit
Montreal, Quebec, H3A 3B4, Canada
Groupe Hospitalier Pellegrin - Hôpital Pellegrin
Bordeaux, 33076, France
CHU CAEN - Hôpital de la Côte de Nacre
Caen, 14033, France
Hopital Roger Salengro - CHU Lille
Lille, 59037, France
CHU Nice - Hôpital Pasteur
Nice, 6001, France
CHU Nantes - Hopital Nord Laënnec
Saint-Herblain, 44800, France
CHU Strasbourg - Nouvel Hôpital Civil
Strasbourg, 67091, France
Neurologie im Alphamed
Bamberg, 96052, Germany
Charité - Campus Charité Mitte
Berlin, 10117, Germany
Katholisches Klinikum Bochum gGmbH
Bochum, 44791, Germany
Neuro Centrum Science GmbH
Erbach im Odenwald, 64711, Germany
Universitaetsklinikum Essen
Essen, 45147, Germany
Universitaetsklinikum Freiburg
Freiburg im Breisgau, 79106, Germany
Universitaetsklinikum Giessen und Marburg GmbH Standort Marburg
Marburg, 35043, Germany
Klinikum rechts der Isar der TU Muenchen
Munich, 81675, Germany
Universitaetsklinikum Muenster
Münster, 48149, Germany
Synconcept GmbH - Neuro MVZ
Stuttgart, 70182, Germany
Chaim Sheba Medical Center
Ramat Gan, 52363, Israel
Azienda Ospedaliero Universitaria Policlinico "Gaspare Rodolico - San Marco" (Presidio G. Rodolico)
Catania, 95123, Italy
Fondazione Istituto G.Giglio di Cefalù
Cefalù, 90015, Italy
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milan, 20133, Italy
Azienda Ospedaliera Universitaria- Università degli Studi della Campania "Luigi Vanvitelli"
Napoli, 80131, Italy
I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo
Pozzilli, 86077, Italy
Amphia Ziekenhuis, Molengracht
Breda, 4818 CK, Netherlands
St. Antonius Ziekenhuis
Nieuwegein, 3435 CM, Netherlands
Zuyderland Medisch Centrum - Sittard-Geleen
Sittard, 6162 BG, Netherlands
Hospital Universitari Arnau de Vilanova
Lleida, Catalonia, 25198, Spain
Hospital Universitario Virgen de la Arrixaca
El Palmar, Murcia, 30120, Spain
Hospital Universitario Ramon y Cajal
Madrid, 28034, Spain
Hospital Regional Universitario de Malaga
Málaga, 29010, Spain
Hospital Universitario Virgen Macarena
Seville, 41009, Spain
King's College Hospital
London, Greater London, SE5 9RS, United Kingdom
The National Hospital for Neurology & Neurosurgery
London, Greater London, WC1N 3BG, United Kingdom
Walton Centre for Neurology & Neurosurgery.
Liverpool, Merseyside, L9 7LJ, United Kingdom
Queen Elizabeth University Hospital Campus
Glasgow, Strathclyde, G51 4TF, United Kingdom
Newcastle University- Clinical Ageing Research Unit
Newcastle upon Tyne, Tyne & Wear, NE4 5PL, United Kingdom
Charing Cross Hospital
London, W6 8RF, United Kingdom
Nottingham University Hospital, Queen's Medical Centre
Nottingham, NG7 2UH, United Kingdom
Salford Care Organisation
Salford, M6 8HD, United Kingdom
Royal Hallamshire Hospital
Sheffield, S10 2JF, United Kingdom
Morriston Hospital
Swansea, SA6 6NL, United Kingdom
Related Publications (3)
Foley JF, Defer G, Ryerson LZ, Cohen JA, Arnold DL, Butzkueven H, Cutter GR, Giovannoni G, Killestein J, Wiendl H, Li K, Dsilva L, Toukam M, Ferber K, Sohn J, Engelman H, Lasky T. Pharmacokinetics and Pharmacodynamics of Natalizumab 6-Week Dosing vs Continued 4-Week Dosing for Relapsing-Remitting Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2024 Dec;11(6):e200321. doi: 10.1212/NXI.0000000000200321. Epub 2024 Oct 11.
PMID: 39393045DERIVEDWiendl H, Foley J, Defer G, Zhovtis Ryerson L, Cohen JA, Arnold DL, Butzkueven H, Cutter GR, Giovannoni G, Killestein J, Domingo-Horne R, Toukam M, Nunn A, Maghzi AH, Kuhelj R, Lasky T. Patient Preference for Subcutaneous Versus Intravenous Administration with Every-6-Week Natalizumab (Tysabri(R)) Dosing: NOVA Phase IIIb Extension Study (Part 2). Neurol Ther. 2024 Oct;13(5):1385-1401. doi: 10.1007/s40120-024-00647-0. Epub 2024 Jul 24.
PMID: 39046635DERIVEDFoley 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.
PMID: 35483387DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- US Biogen Clinical Trial Center
- Organization
- Biogen
Study Officials
- STUDY DIRECTOR
Medical Director
Biogen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 27, 2018
First Posted
October 1, 2018
Study Start
November 27, 2018
Primary Completion
January 31, 2023
Study Completion
July 24, 2023
Last Updated
June 12, 2024
Results First Posted
June 12, 2024
Record last verified: 2024-05
Data Sharing
- IPD Sharing
- Will not share
Please refer data queries to DataSharing@biogen.com.