Clinical trial NCT00536120: The Effects of Tysabri Treatment on Vaccination Response and Lymphocyte Subsets in Subjects With Relapsing Forms of Multiple Sclerosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Sclerosis
Keywords: MS
Multiple sclerosis
Relapsing forms of Multiple Sclerosis
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2007-09-27
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.


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

Primary outcomes:
measure: Percentage of Keyhole Limpet Hemocyanin (KLH) Responders at Day 28 Post-Vaccination
timeFrame: 28 days after immunization (Day 28 for Vaccinations Only Group/Day 196 for Tysabri Plus Vaccinations Group)
measure: Percentage of Tetanus Diphtheria Toxoid (Td) Responders at Day 28 Post-Vaccination
timeFrame: 28 days after immunization (Day 28 for Vaccinations Only Group/Day 196 for Tysabri Plus Vaccinations Group)
Secondary outcomes:
measure: Mean Percentage Change From Baseline in Circulating Lymphocyte Subsets CD3+, CD4+, CD8+, CD19+, and CD56+ at Month 3 of Tysabri Therapy
timeFrame: Month 0 (Baseline), Month 3
measure: Mean Percentage Change From Baseline in Circulating Lymphocyte Subsets CD3+, CD4+, CD8+, CD19+, and CD56+ at Month 6 of Tysabri Therapy
timeFrame: Month 0 (Baseline), Month 6
measure: Mean Alpha4-Integrin Saturation at Baseline, Month 3, and Month 6
timeFrame: Month 0 (Baseline), Month 3, and Month 6
measure: Mean Alpha4-Integrin Expression at Baseline, Month 3, and Month 6
timeFrame: Month 0 (Baseline), Month 3, and Month 6
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: Research Site 1
state: California
city: Centennial
country: United States
facility: Research Site
state: Colorado
city: Farmington Hills
country: United States
facility: Research site
state: Michigan
city: Patchogue
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site 3
state: North Carolina
city: Oklahoma City
country: United States
facility: Research Site 5
state: Oklahoma
city: Franklin
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Seattle
country: United States
facility: Research Site 2
state: Washington
city: Charleston
country: United States
facility: Research Site 4
state: West Virginia
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.