Safety and Efficacy of Natalizumab in the Treatment of Multiple Sclerosis

NCT00027300 | Completed Phase 3 DMC

• 1 other identifier: C-1801
• Study Type: interventional
• Target: 900
• Locations: 8 countries
• Sites: 53

Brief Summary

The purpose of this study is to determine the safety and efficacy of natalizumab in the treatment of individuals who have been diagnosed with relapsing remitting multiple sclerosis (MS). It is hoped that natalizumab will prevent certain types of white blood cells from moving out of the bloodstream into organs, including the brain, that are being damaged by autoimmune disease (a disease in which the body's own immune system attacks certain organs). These white blood cells are thought to cause inflammation that can result in lesions (small areas of damage) in the brain. These lesions are thought to be the cause of relapses and disability in MS.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

Relapsing Remitting Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• The primary objectives of this study are to determine whether natalizumab, when compared with placebo, is effective in reducing the rate of clinical relapses at 1 year and, in slowing the progression of disability at 2 years.

  1 year and 2 years

Secondary Outcomes (1)

• Reduction in MRI changes and clinical relapses

  1 year

Study Arms (2)

Group 1

EXPERIMENTAL

Natalizumab 300 mg, IV

Drug: Natalizumab

Group 2

PLACEBO COMPARATOR

Placebo IV infusion

Drug: Placebo

Interventions

Natalizumab DRUG

Natalizumab 300 mg IV infusion, every 4 weeks, for up to 116 weeks.

Also known as: Tysabri

Group 1

Placebo DRUG

Placebo, IV infusion, every 4 weeks, for up to 116 weeks.

Group 2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of MS, as defined by McDonald et al., criteria # 1-4 (McDonald et al., 2001)
• Between the ages of 18 and 50, inclusive.
• Baseline EDSS score between 0.0 and 5.0, inclusive.
• Have experienced at least one relapse within the 12 months prior to randomization.
• Cranial MRI scan demonstrating lesion(s) consistent with MS.
• Have given written informed consent to participate in the study.

You may not qualify if:

• Primary progressive, secondary progressive, or progressive relapsing MS.
• MS relapse has occurred,in the opinion of the investigator, within 50 days prior to randomization and/or the subject has not stabilized from a previous relapse.
• A clinically significant infectious illness within 30 days prior to randomization.
• History of, or abnormal laboratory results indicative of any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal and/or other major disease, that in the opinion of the investigator, would preclude the administration of a recombinant humanized antibody immunomodulating agent for 116 weeks.
• History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
• Unable to perform the Timed 25-foot Walk, 9HPT, and PASAT 3.
• Abnormal blood tests performed at the Screening Visit.

Sponsors & Collaborators

• Biogen: lead
• Elan Pharmaceuticals: collaborator

Study Sites (53)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259, United States

Location

East Bay Region Associates in Neurology

Berkeley, California, 94705, United States

Location

UC Davis School of Medicine, Department of Neurology

Davis, California, 95817-2307, United States

Location

Yale University School of Medicine, Department of Neurology

New Haven, Connecticut, 06510, United States

Location

University of Miami School of Medicine, Department of Neurology

Miami, Florida, 33136, United States

Location

University of Kansas Medical Center, Department of Neurology

Kansas City, Kansas, 66160, United States

Location

Michigan Institute for Neurological Disorders

Farmington Hills, Michigan, 48335, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Gimbel MS Center

Teaneck, New Jersey, 07666, United States

Location

CMRRC

Albuquerque, New Mexico, 87131, United States

Location

Oregon Health Sciences University, Department of Neurology

Portland, Oregon, 97201-3098, United States

Location

Lehigh Valley Hospital, Neurosciences Research

Allentown, Pennsylvania, 18103, United States

Location

Texas Neurology

Dallas, Texas, 75214, United States

Location

University of Washington MS Research Center

Seattle, Washington, 98195, United States

Location

Algemeen Ziekenhuis St. Jan

Bruges, 8000, Belgium

Location

LUC- University Centre

Diepenbeek, 3590, Belgium

Location

National MS Centrum

Melsbroek, 1820, Belgium

Location

Vancouver Hospital and Health Sciences Center UBC Pavilion, MS Clinical Research Group

Vancouver, British Columbia, V6T 2B5, Canada

Location

Health Services Centre

Winnipeg, Manitoba, R3A 1R9, Canada

Location

Kingston General Hospital, Neurology

Kingston, Ontario, K7L 2V7, Canada

Location

University Hospital

London, Ontario, N6A 5A5, Canada

Location

Sunnybrook and Women's College and Health Science Centre

Toronto, Ontario, M4N 3M5, Canada

Location

University of Toronto, MS Clinic, St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

CHVO Hull Hospital

Québec, Quebec, J8Y 1W7, Canada

Location

MS Research Unit, Center for Clinical Research

Halifax, B3H 1V7, Canada

Location

Family Medical Centre

Ottawa, K1N 5C7, Canada

Location

Faculty Hospital Brno Bohunice

Brno, 60200, Czechia

Location

Faculty Hospital St. Anne

Brno, 656 91, Czechia

Location

Faculty Hospital of Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Faculty Hospital Olomouc

Olomouc, 775 20, Czechia

Location

Faculty Hospital Of Ostrava Poruba

Ostrava, 70852, Czechia

Location

Hospital Pardubice - Department of Neurology

Pardubice, 532 03, Czechia

Location

Faculty Hospital Plzen - Clinic of Neurology

Pilsen, 304 60, Czechia

Location

General Teaching Hospital - Neurological Department

Prague, 2 12802, Czechia

Location

Faculty Hospital Motol - Neurological Clinic

Prague, 5 105 06, Czechia

Location

Hopital de la Timone, Service de Neurologie

Marseille, 13385, France

Location

CHRU - Hopital de Pontchaillou, Service de Neurologie

Rennes, 35033, France

Location

St. Josef-Hospital, Neurologische Klinik der Ruhruniversitat Bochum

Bochurn, 44791, Germany

Location

Klinika Neurologii

Bydgoszcz, 85-681, Germany

Location

Academisch Ziekenhuis VU

Amsterdam, 1081 HV, Netherlands

Location

Institute of Neurology

Queen Square, London, WC1N 3BG, United Kingdom

Location

The Royal London Hospital

Whitechapel, London, E1 1BB, United Kingdom

Location

Atkin's Morely Hospital

Wimbledon, London, SW20 0NE, United Kingdom

Location

Oldchurch Hospital

Essex, NE1 4LP, United Kingdom

Location

Ipswich Hospital NHS Trust - Department of Clinical Neurology

Ipswich, IP4 5PD, United Kingdom

Location

St. James University Hospital, Department of Neurology

Leeds, LS9 7TF, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

Kings College Hospital, Kings Neuroscience Center

London, SE5 9RS, United Kingdom

Location

Royal Victoria Infirmary

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

The Radcliffe Infirmary, University Department of Clinical Neurology

Oxford, OX2 0HE, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

Location

North Staffordshire Royal Infirmary - Neurology Department

Stoke-on-Trent, ST4 7LN, United Kingdom

Location

Related Publications (5)

• Voloshyna N, Havrdova E, Hutchinson M, Nehrych T, You X, Belachew S, Hotermans C, Paes D. Natalizumab improves ambulation in relapsing-remitting multiple sclerosis: results from the prospective TIMER study and a retrospective analysis of AFFIRM. Eur J Neurol. 2015 Mar;22(3):570-7. doi: 10.1111/ene.12618. Epub 2014 Dec 15.

  PMID: 25511792 BACKGROUND

• Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006 Mar 2;354(9):899-910. doi: 10.1056/NEJMoa044397.

  PMID: 16510744 RESULT

• Nakamura K, Sun Z, Hara-Cleaver C, Bodhinathan K, Avila RL. Natalizumab reduces loss of gray matter and thalamic volume in patients with relapsing-remitting multiple sclerosis: A post hoc analysis from the randomized, placebo-controlled AFFIRM trial. Mult Scler. 2024 May;30(6):687-695. doi: 10.1177/13524585241235055. Epub 2024 Mar 12.

  PMID: 38469809 DERIVED

• Strijbis EM, Coerver E, Mostert J, van Kempen ZLE, Killestein J, Comtois J, Repovic P, Bowen JD, Cutter G, Koch M. Association of age and inflammatory disease activity in the pivotal natalizumab clinical trials in relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2023 Oct;94(10):792-799. doi: 10.1136/jnnp-2022-330887. Epub 2023 May 12.

  PMID: 37173129 DERIVED

• Balcer LJ, Galetta SL, Polman CH, Eggenberger E, Calabresi PA, Zhang A, Scanlon JV, Hyde R. Low-contrast acuity measures visual improvement in phase 3 trial of natalizumab in relapsing MS. J Neurol Sci. 2012 Jul 15;318(1-2):119-24. doi: 10.1016/j.jns.2012.03.009. Epub 2012 Apr 21.

  PMID: 22521274 DERIVED

Related Links

• The web site of the National Multiple Sclerosis Society, an organization dedicated to providing information to individuals with MS, their families and healthcare providers
• MSActiveSource.com is a resource for news, information and disease management for all individuals touched by multiple sclerosis. This site is sponsored by Biogen.

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Natalizumab

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Michael Panzara, MD, MPH

  Biogen

  STUDY DIRECTOR

• Chris Polman, MD

  VU Medical Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: November 30, 2001
• First Posted: December 3, 2001
• Study Start: November 1, 2001
• Primary Completion: November 1, 2004
• Study Completion: January 1, 2005
• Last Updated: January 9, 2017

Record last verified: 2017-01

Locations

DE (2); CZ (9); US (14); GB (13); BE (3); CA (9); NL (1); FR (2)