The Effects of Tysabri Treatment on Vaccination Response and Lymphocyte Subsets in Subjects With Relapsing Forms of Multiple Sclerosis

Biogen

Status and phase: Completed; Phase 4

Conditions: Multiple Sclerosis

Treatments: Biological: tetanus diphtheria toxoid vaccine (Td); Biological: keyhole limpet hemocyanin (KLH); Biological: BG00002 (natalizumab)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00536120

101MS404

Details and patient eligibility

About

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.

Enrollment: 60 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

60 participants in 2 patient groups

Tysabri Plus Vaccinations

Experimental group

Description:

Participants 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.

Treatment:

Biological: BG00002 (natalizumab)

Biological: keyhole limpet hemocyanin (KLH)

Biological: tetanus diphtheria toxoid vaccine (Td)

Vaccinations Only

Other group

Description:

Participants 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.

Treatment:

Biological: keyhole limpet hemocyanin (KLH)

Biological: tetanus diphtheria toxoid vaccine (Td)