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

NCT ID: NCT03689972

Last Updated: 2024-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 585 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-27
• Study Completion Date: 2023-07-24

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.

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.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: IV Q4W

Participants received natalizumab 300 mg intravenous (IV) infusion once Q4W up to Week 72.

Group Type: EXPERIMENTAL

Natalizumab

Intervention Type: DRUG

Natalizumab 300 mg IV infusion.

Part 1: IV Q6W

Participants received natalizumab 300 mg IV infusion once Q6W up to Week 72.

Group Type: EXPERIMENTAL

Natalizumab

Intervention Type: DRUG

Natalizumab 300 mg IV infusion.

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.

Group Type: EXPERIMENTAL

Natalizumab

Intervention Type: DRUG

Natalizumab 300 mg IV infusion.

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.

Group Type: EXPERIMENTAL

Natalizumab

Intervention Type: DRUG

Natalizumab 300 mg SC injection or IV infusion.

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.

Group Type: EXPERIMENTAL

Natalizumab

Intervention Type: DRUG

Natalizumab 300 mg SC injection or IV infusion.

Interventions

Natalizumab

Natalizumab 300 mg IV infusion.

Intervention Type: DRUG

Natalizumab

Natalizumab 300 mg SC injection or IV infusion.

Intervention Type: DRUG

Other Intervention Names

BG00002; BG00002

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biogen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Biogen

Locations

North Central Neurology Associates, P.C.

Cullman, Alabama, United States

Alabama Neurology Associates

Homewood, Alabama, United States

UCI MIND

Irvine, California, United States

UC San Diego Movement Disorder Center

La Jolla, California, United States

MS Center of California

Laguna Hills, California, United States

Stanford Hospital and Clinics

Palo Alto, California, United States

University of Colorado Hospital Anschutz Outpatient Pavillion

Aurora, Colorado, United States

Advanced Neurosciences Research

Fort Collins, Colorado, United States

Yale University

Fairfield, Connecticut, United States

Georgetown University Hospital-Medstar

Washington D.C., District of Columbia, United States

University of Miami Miller School of Medicine

Miami, Florida, United States

Infinity Clinical Research, LLC

Sunrise, Florida, United States

University of South Florida

Tampa, Florida, United States

Shepherd Center, Inc.

Atlanta, Georgia, United States

Atlanta Neuroscience Institute

Atlanta, Georgia, United States

NorthShore University HealthSystem

Evanston, Illinois, United States

Northwestern University

Evanston, Illinois, United States

College Park Family Care Center

Overland Park, Kansas, United States

Lahey Clinic Inc. - PARENT ACCOUNT

Burlington, Massachusetts, United States

Neurology Center of New England P.C.

Foxborough, Massachusetts, United States

Beth Israel Deaconess Medical Center, Inc.

Jamaica Plain, Massachusetts, United States

Dragonfly Research, LLC

Wellesley, Massachusetts, United States

South Shore Neurology Associates

Weymouth, Massachusetts, United States

Michigan Institute for Neurological Disorders

Farmington Hills, Michigan, United States

Michigan State University

Grand Rapids, Michigan, United States

Memorial Healthcare

Owosso, Michigan, United States

Minneapolis Clinic of Neurology

Golden Valley, Minnesota, United States

Washington University, School of Medicine

St Louis, Missouri, United States

Cleveland Clinic Lou Ruvo Center for Brain Health

Las Vegas, Nevada, United States

RWJ Barnabas Health

Newark, New Jersey, United States

Holy Name Medical Center

Teaneck, New Jersey, United States

NYU Langone Clinical Cancer Center

New York, New York, United States

Mount Sinai Medical Center

New York, New York, United States

Columbia University Hervert Irving Comprehensive Cancer Center

New York, New York, United States

Island Neurological Associates, P.C.

Plainview, New York, United States

Raleigh Neurology Associates

Raleigh, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

University of Cincinnati

Cincinnati, Ohio, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

OhioHealth Riverside Methodist Hospital

Columbus, Ohio, United States

Dayton Center for Neurological Disorders

Dayton, Ohio, United States

Providence Neurological Specialties

Portland, Oregon, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Magee-Womens Hospital of UPMC

Pittsburgh, Pennsylvania, United States

Sibyl Wray, MD Neurology, PC

Knoxville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Central Texas Neurology Consultants

Round Rock, Texas, United States

Rocky Mountain MS Research Group LLC

Salt Lake City, Utah, United States

University Of Virginia

Charlottesville, Virginia, United States

Multiple Sclerosis Center of Greater Washington

Vienna, Virginia, United States

Virginia Mason Medical Center

Seattle, Washington, United States

Wheaton Franciscan Healthcare

Milwaukee, Wisconsin, United States

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Brain and Mind Centre

Sydney, New South Wales, Australia

Lyell McEwin Hospital

Elizabeth Vale, South Australia, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Cliniques Universitaires de Bruxelles Hopital Erasme

Brussels, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

UZA

Edegem, , Belgium

CHU de Tivoli

La Louvière, , Belgium

St. Michael's Hospital

Toronto, Ontario, Canada

Clinique Neuro-Outaouais

Gatineau, Quebec, Canada

Recherche SEPMUS

Greenfield Park, Quebec, Canada

CHUM Centre de Recherche

Montreal, Quebec, Canada

Montreal Neurological Institute Clinical Research Unit

Montreal, Quebec, Canada

Groupe Hospitalier Pellegrin - Hôpital Pellegrin

Bordeaux, , France

CHU CAEN - Hôpital de la Côte de Nacre

Caen, , France

Hopital Roger Salengro - CHU Lille

Lille, , France

CHU Nice - Hôpital Pasteur

Nice, , France

CHU Nantes - Hopital Nord Laënnec

Saint-Herblain, , France

CHU Strasbourg - Nouvel Hôpital Civil

Strasbourg, , France

Neurologie im Alphamed

Bamberg, , Germany

Charité - Campus Charité Mitte

Berlin, , Germany

Katholisches Klinikum Bochum gGmbH

Bochum, , Germany

Neuro Centrum Science GmbH

Erbach im Odenwald, , Germany

Universitaetsklinikum Essen

Essen, , Germany

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

Universitaetsklinikum Giessen und Marburg GmbH Standort Marburg

Marburg, , Germany

Klinikum rechts der Isar der TU Muenchen

Munich, , Germany

Universitaetsklinikum Muenster

Münster, , Germany

Synconcept GmbH - Neuro MVZ

Stuttgart, , Germany

Chaim Sheba Medical Center

Ramat Gan, , Israel

Azienda Ospedaliero Universitaria Policlinico "Gaspare Rodolico - San Marco" (Presidio G. Rodolico)

Catania, , Italy

Fondazione Istituto G.Giglio di Cefalù

Cefalù, , Italy

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, , Italy

Azienda Ospedaliera Universitaria- Università degli Studi della Campania "Luigi Vanvitelli"

Napoli, , Italy

I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo

Pozzilli, , Italy

Amphia Ziekenhuis, Molengracht

Breda, , Netherlands

St. Antonius Ziekenhuis

Nieuwegein, , Netherlands

Zuyderland Medisch Centrum - Sittard-Geleen

Sittard, , Netherlands

Hospital Universitari Arnau de Vilanova

Lleida, Catalonia, Spain

Hospital Universitario Virgen de la Arrixaca

El Palmar, Murcia, Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital Regional Universitario de Malaga

Málaga, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

King's College Hospital

London, Greater London, United Kingdom

The National Hospital for Neurology & Neurosurgery

London, Greater London, United Kingdom

Walton Centre for Neurology & Neurosurgery.

Liverpool, Merseyside, United Kingdom

Queen Elizabeth University Hospital Campus

Glasgow, Strathclyde, United Kingdom

Newcastle University- Clinical Ageing Research Unit

Newcastle upon Tyne, Tyne & Wear, United Kingdom

Charing Cross Hospital

London, , United Kingdom

Nottingham University Hospital, Queen's Medical Centre

Nottingham, , United Kingdom

Salford Care Organisation

Salford, , United Kingdom

Royal Hallamshire Hospital

Sheffield, , United Kingdom

Morriston Hospital

Swansea, , United Kingdom

Countries

United States; Australia; Belgium; Canada; France; Germany; Israel; Italy; Netherlands; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39393045 (View on PubMed)

Wiendl 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.

Reference Type: DERIVED

PMID: 39046635 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35483387 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-002145-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

101MS329

Identifier Type: -

Identifier Source: org_study_id