Safety and Efficacy of Natalizumab in the Treatment of Multiple Sclerosis

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00027300
• Other study ID #: C-1801
• Status: Completed
• Phase: Phase 3
• First received: November 30, 2001
• Last updated: January 5, 2017
• Start date: November 2001
• Est. completion date: January 2005

Study information

• Verified date: January 2017
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 900
• Est. completion date: January 2005
• Est. primary completion date: November 2004
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• Natalizumab
Natalizumab 300 mg IV infusion, every 4 weeks, for up to 116 weeks.
• Placebo
Placebo, IV infusion, every 4 weeks, for up to 116 weeks.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Biogen	Elan Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czech Republic,  France,  Germany,  Netherlands,  United Kingdom, 

References & Publications (2)

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 multi — View Citation

Voloshyna N, Havrdová 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Reduction in MRI changes and clinical relapses		1 year	No

External Links

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