Clinical trial NCT00027300: Safety and Efficacy of Natalizumab in the Treatment of Multiple Sclerosis
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Determine the Safety and Efficacy of Natalizumab in Subjects With Relapsing-Remitting Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis, Relapsing-Remitting
Keywords: Relapsing Remitting Multiple Sclerosis
Lead sponsor: Biogen
Sponsor class: INDUSTRY
Collaborators: name: Elan Pharmaceuticals
First posted: 2001-12-03
Enrollment: 900
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: 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.
timeFrame: 1 year and 2 years
Secondary outcomes:
measure: Reduction in MRI changes and clinical relapses
timeFrame: 1 year
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Berkeley
country: United States
facility: East Bay Region Associates in Neurology
state: California
city: Davis
country: United States
facility: UC Davis School of Medicine, Department of Neurology
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine, Department of Neurology
state: Connecticut
city: Miami
country: United States
facility: University of Miami School of Medicine, Department of Neurology
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center, Department of Neurology
state: Kansas
city: Farmington Hills
country: United States
facility: Michigan Institute for Neurological Disorders
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Teaneck
country: United States
facility: Gimbel MS Center
state: New Jersey
city: Albuquerque
country: United States
facility: CMRRC
state: New Mexico
city: Portland
country: United States
facility: Oregon Health Sciences University, Department of Neurology
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Hospital, Neurosciences Research
state: Pennsylvania
city: Dallas
country: United States
facility: Texas Neurology
state: Texas
city: Seattle
country: United States
facility: University of Washington MS Research Center
state: Washington
city: Brugge
country: Belgium
facility: Algemeen Ziekenhuis St. Jan
city: Diepenbeek
country: Belgium
facility: LUC- University Centre
city: Melsbroek
country: Belgium
facility: National MS Centrum
city: Vancouver
country: Canada
facility: Vancouver Hospital and Health Sciences Center UBC Pavilion, MS Clinical Research Group
state: British Columbia
city: Winnipeg
country: Canada
facility: Health Services Centre
state: Manitoba
city: Kingston
country: Canada
facility: Kingston General Hospital, Neurology
state: Ontario
city: London
country: Canada
facility: University Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook and Women's College and Health Science Centre
state: Ontario
city: Toronto
country: Canada
facility: University of Toronto, MS Clinic, St. Michael's Hospital
state: Ontario
city: Quebec City
country: Canada
facility: CHVO Hull Hospital
state: Quebec
city: Halifax
country: Canada
facility: MS Research Unit, Center for Clinical Research
city: Ottawa
country: Canada
facility: Family Medical Centre
city: Brno
country: Czech Republic
facility: Faculty Hospital Brno Bohunice
city: Brno
country: Czech Republic
facility: Faculty Hospital St. Anne
city: Hradec Kralove
country: Czech Republic
facility: Faculty Hospital of Hradec Kralove
city: Olomouc
country: Czech Republic
facility: Faculty Hospital Olomouc
city: Ostrava
country: Czech Republic
facility: Faculty Hospital Of Ostrava Poruba
city: Pardubice
country: Czech Republic
facility: Hospital Pardubice - Department of Neurology
city: Plzen
country: Czech Republic
facility: Faculty Hospital Plzen - Clinic of Neurology
city: Prague
country: Czech Republic
facility: General Teaching Hospital - Neurological Department
city: Prague
country: Czech Republic
facility: Faculty Hospital Motol - Neurological Clinic
city: Marseille
country: France
facility: Hopital de la Timone, Service de Neurologie
city: Rennes
country: France
facility: CHRU - Hopital de Pontchaillou, Service de Neurologie
city: Bochurn
country: Germany
facility: St. Josef-Hospital, Neurologische Klinik der Ruhruniversitat Bochum
city: Bydgoszcz
country: Germany
facility: Klinika Neurologii
city: Amsterdam
country: Netherlands
facility: Academisch Ziekenhuis VU
city: Queen Square
country: United Kingdom
facility: Institute of Neurology
state: London
city: Whitechapel
country: United Kingdom
facility: The Royal London Hospital
state: London
city: Wimbledon
country: United Kingdom
facility: Atkin's Morely Hospital
state: London
city: Essex
country: United Kingdom
facility: Oldchurch Hospital
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital NHS Trust - Department of Clinical Neurology
city: Leeds
country: United Kingdom
facility: St. James University Hospital, Department of Neurology
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Kings College Hospital, Kings Neuroscience Center
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Oxford
country: United Kingdom
facility: The Radcliffe Infirmary, University Department of Clinical Neurology
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
city: Stoke on Trent
country: United Kingdom
facility: North Staffordshire Royal Infirmary - Neurology Department
Study officials:
affiliation: Biogen
name: Michael Panzara, MD, MPH
role: STUDY_DIRECTOR
affiliation: VU Medical Centre
name: Chris Polman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.