Safety and Efficacy of Natalizumab in the Treatment of Multiple Sclerosis

• ClinicalTrials.gov Identifier: NCT00027300
• Recruitment Status: Completed
• First Posted: December 3, 2001
• Last Update Posted: January 9, 2017
• Sponsor: Biogen
• Collaborator: Elan Pharmaceuticals
• Information provided by: Biogen

Tracking Information

• First Submitted Date: November 30, 2001
• First Posted Date: December 3, 2001
• Last Update Posted Date: January 9, 2017
• Study Start Date: November 2001
• Actual Primary Completion Date: November 2004 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 15, 2009): 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. [ Time Frame: 1 year and 2 years ]
• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures (submitted: June 15, 2009): Reduction in MRI changes and clinical relapses [ Time Frame: 1 year ]
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Multiple Sclerosis, Relapsing-Remitting

Intervention

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

Study Arms

• Experimental: Group 1
  Natalizumab 300 mg, IV
  Intervention: Drug: Natalizumab
• Placebo Comparator: Group 2
  Placebo IV infusion
  Intervention: Drug: Placebo

Publications *

• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 12, 2006): 900
• Original Enrollment: Not Provided
• Actual Study Completion Date: January 2005
• Actual Primary Completion Date: November 2004 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, Czech Republic, France, Germany, Netherlands, United Kingdom, United States

Administrative Information

• NCT Number: NCT00027300
• Other Study ID Numbers: C-1801
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Biogen Idec Medical Director, Biogen Idec
• Original Responsible Party: Not Provided
• Current Study Sponsor: Biogen
• Original Study Sponsor: Same as current
• Collaborators: Elan Pharmaceuticals

Investigators

• Study Director: Michael Panzara, MD, MPH; Biogen
• Principal Investigator: Chris Polman, MD; VU Medical Centre

• PRS Account: Biogen
• Verification Date: January 2017