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

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.

Inclusion Criteria:

• 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

Major Exclusion Criteria:

• 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
• treatment with cyclophosphamide within 1 year prior to screening
• treatment with immunomodulatory medications (interferon beta and glatiramer acetate) within 2 weeks prior to screening
• treatment with systemic corticosteroids within 4 weeks prior to screening
• treatment with any investigational product or approved therapy or vaccination for investigational use within 6 months prior to Screening
• women who are breastfeeding, pregnant, or planning to become pregnant during the study
• female subjects who are not postmenopausal for at least 1 year, surgically sterile (does not include tubal ligation), or willing to practice effective contraception during the study