The Effects of Tysabri Treatment on Vaccination Response and Lymphocyte Subsets in Subjects With Relapsing Forms of Multiple Sclerosis
A Randomized, Open-Label Study to Assess the Effects of Tysabri Treatment on Vaccination Response and Lymphocyte Subsets in Subjects With Relapsing Forms of Multiple Sclerosis
1 other identifier
interventional
60
1 country
10
Brief Summary
The primary objectives of this study were: to evaluate the effect of Tysabri® (natalizumab) on antibody responses after immunization with a neoantigen (keyhole limpet hemocyanin \[KLH\]) and a recall antigen (tetanus toxoid \[Td\]), and to evaluate the effect of Tysabri on circulating lymphocyte subsets (CD3+, CD4+, CD8+, CD19+, and CD56+) over time in participants with relapsing forms of multiple sclerosis (MS). The secondary objective was to assess alpha4-integrin saturation and alpha4-integrin expression levels over time.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_4 multiple-sclerosis
Started Jan 2008
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 25, 2007
CompletedFirst Posted
Study publicly available on registry
September 27, 2007
CompletedStudy Start
First participant enrolled
January 1, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2009
CompletedResults Posted
Study results publicly available
July 29, 2011
CompletedFebruary 15, 2017
December 1, 2016
1.8 years
September 25, 2007
March 17, 2011
December 29, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Percentage of Keyhole Limpet Hemocyanin (KLH) Responders at Day 28 Post-Vaccination
KLH responders were defined as those participants who had at least a 2-fold increase over pre-immunization level of anti-KLH antibodies in their blood at 28 days after vaccination with KLH.
28 days after immunization (Day 28 for Vaccinations Only Group/Day 196 for Tysabri Plus Vaccinations Group)
Percentage of Tetanus Diphtheria Toxoid (Td) Responders at Day 28 Post-Vaccination
Tetanus responders were defined as participants who had at least a 2-fold increase over pre-immunization levels of anti-tetanus antibodies in their blood at 28 days after they were immunized with tetanus.
28 days after immunization (Day 28 for Vaccinations Only Group/Day 196 for Tysabri Plus Vaccinations Group)
Secondary Outcomes (4)
Mean Percentage Change From Baseline in Circulating Lymphocyte Subsets CD3+, CD4+, CD8+, CD19+, and CD56+ at Month 3 of Tysabri Therapy
Month 0 (Baseline), Month 3
Mean Percentage Change From Baseline in Circulating Lymphocyte Subsets CD3+, CD4+, CD8+, CD19+, and CD56+ at Month 6 of Tysabri Therapy
Month 0 (Baseline), Month 6
Mean Alpha4-Integrin Saturation at Baseline, Month 3, and Month 6
Month 0 (Baseline), Month 3, and Month 6
Mean Alpha4-Integrin Expression at Baseline, Month 3, and Month 6
Month 0 (Baseline), Month 3, and Month 6
Study Arms (2)
Tysabri Plus Vaccinations
EXPERIMENTALParticipants receive 9 monthly doses of Tysabri 300 mg intravenous (IV), and receive vaccinations with neoantigen and recall antigen (keyhole limpet hemocyanin \[KLH\] and tetanus diphtheria toxoid \[Td\], according to manufacturer's prescribing information) at Month 6 (following the 7th dose of Tysabri) for both KLH and Td, and 14 and 28 days later for KLH.
Vaccinations Only
OTHERParticipants receive only vaccinations with neoantigen and recall antigen (KLH and Td, according to manufacturer's prescribing information) at Month 0 for both KLH and Td, and 14 and 28 days later for KLH. They do not receive any treatment for their MS and remain in the study through Month 2.
Interventions
KLH 1 mg administered subcutaneously (SC) in accordance with the Immucothel investigator's brochure.
Td administered in accordance with the manufacturer's prescribing information.
Eligibility Criteria
You may qualify if:
- able to give written informed consent
- diagnosis of a relapsing form of MS and must fall within the therapeutic indication stated in the approved label for Tysabri
- aged 18-60 years, inclusive at the time of consent
- free of signs and symptoms suggestive of any serious opportunistic infection, based on medical history, physical examination, or laboratory testing
- must have a known history of tetanus toxoid immunization
You may not qualify if:
- tetanus toxoid vaccination less than 2 years prior to Screening
- known hypersensitivity to tetanus-diphtheria vaccine or KLH or any other administered vaccinations or their components (such as thimerosal)
- known allergy to shellfish
- history of active tuberculosis or undergoing treatment for tuberculosis
- previous exposure to KLH or vaccines containing KLH components (e.g., cancer vaccines)
- known history of human immunodeficiency virus (HIV), hepatitis C, or hepatitis B infection
- history of, or available abnormal laboratory results indicative of any significant disease
- history of malignancy
- history of organ transplantation (including anti-rejection therapy)
- history of severe allergic or anaphylactic reactions or known drug hypersensitivity
- a clinically significant infectious illness within 30 days prior to the Screening visit
- prior exposure to Tysabri, rituximab, any murine protein, or any therapeutic monoclonal antibody at any time
- receipt of intravenous (IV) or intramuscular (IM) immunoglobulin within 6 months of screening
- live virus, bacterial vaccines, or any other vaccines within 3 months of screening
- treatment with immunosuppressant medications within 6 months prior to screening
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Biogenlead
Study Sites (10)
Research Site 1
Fullerton, California, 92835, United States
Research Site
Centennial, Colorado, 80112, United States
Research site
Farmington Hills, Michigan, 48334, United States
Research Site
Patchogue, New York, 11772, United States
Research Site 3
Charlotte, North Carolina, 28207, United States
Research Site 5
Oklahoma City, Oklahoma, 73130, United States
Research Site
Franklin, Tennessee, 37064, United States
Research Site
Dallas, Texas, 75214, United States
Research Site 2
Seattle, Washington, 98122, United States
Research Site 4
Charleston, West Virginia, 25301, United States
Related Publications (1)
Kaufman M, Pardo G, Rossman H, Sweetser MT, Forrestal F, Duda P. Natalizumab treatment shows no clinically meaningful effects on immunization responses in patients with relapsing-remitting multiple sclerosis. J Neurol Sci. 2014 Jun 15;341(1-2):22-7. doi: 10.1016/j.jns.2014.03.035. Epub 2014 Mar 26.
PMID: 24731783BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Biogen Idec Medical Director
- Organization
- Biogen Idec Inc.
Study Officials
- STUDY DIRECTOR
Medical Director
Biogen
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 25, 2007
First Posted
September 27, 2007
Study Start
January 1, 2008
Primary Completion
November 1, 2009
Study Completion
December 1, 2009
Last Updated
February 15, 2017
Results First Posted
July 29, 2011
Record last verified: 2016-12