The Effects of Tysabri Treatment on Vaccination Response and Lymphocyte Subsets in Subjects With Relapsing Forms of Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: BG00002 (natalizumab); keyhole limpet hemocyanin (KLH); tetanus diphtheria toxoid vaccine (Td)
Intervention description: KLH 1 mg administered subcutaneously (SC) in accordance with the Immucothel investigator's brochure.; Td administered in accordance with the manufacturer's prescribing information.
Intervention MeSH terms: Natalizumab; Keyhole-limpet hemocyanin
Phase: Phase 4
Study type: Interventional
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: MS; Multiple sclerosis; Relapsing forms of Multiple Sclerosis

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.
    

Eligibility criteria:

        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