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

Multiple Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00536120
• Other study ID #: 101MS404
• Status: Completed
• Phase: Phase 4
• First received: September 25, 2007
• Last updated: March 27, 2014
• Start date: January 2008
• Est. completion date: December 2009

Study information

• Verified date: March 2014
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Biological:
• BG00002 (natalizumab)

• keyhole limpet hemocyanin (KLH)
KLH 1 mg administered subcutaneously (SC) in accordance with the Immucothel investigator's brochure.
• tetanus diphtheria toxoid vaccine (Td)
Td administered in accordance with the manufacturer's prescribing information.

Locations

Country	Name	City	State
United States	Research Site	Centennial	Colorado
United States	Research Site 4	Charleston	West Virginia
United States	Research Site 3	Charlotte	North Carolina
United States	Research Site	Dallas	Texas
United States	Research site	Farmington Hills	Michigan
United States	Research Site	Franklin	Tennessee
United States	Research Site 1	Fullerton	California
United States	Research Site 5	Oklahoma City	Oklahoma
United States	Research Site	Patchogue	New York
United States	Research Site 2	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Primary	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)	No
Secondary	Mean Percentage Change From Baseline in Circulating Lymphocyte Subsets CD3+, CD4+, CD8+, CD19+, and CD56+ at Month 3 of Tysabri Therapy	The effect of Tysabri on circulating lymphocyte subsets (CD3+, CD4+, CD8+, CD19+, and CD56+) was calculated as a percentage change from baseline pre-treatment values (based on absolute count).	Month 0 (Baseline), Month 3	No
Secondary	Mean Percentage Change From Baseline in Circulating Lymphocyte Subsets CD3+, CD4+, CD8+, CD19+, and CD56+ at Month 6 of Tysabri Therapy	The effect of Tysabri on circulating lymphocyte subsets (CD3+, CD4+, CD8+, CD19+, and CD56+) was calculated as a percentage change from baseline pre-treatment values (based on absolute count).	Month 0 (Baseline), Month 6	No
Secondary	Mean Alpha4-Integrin Saturation at Baseline, Month 3, and Month 6	Measurement of the degree of natalizumab saturation of the alpha4 integrin on peripheral blood mononuclear cells was accomplished by staining cells with phycoerythrin conjugated anti human IgG4 antibody (hIgG4-PE) to label the cell-bound natalizumab, followed by flow cytometric detection and quantification.	Month 0 (Baseline), Month 3, and Month 6	No
Secondary	Mean Alpha4-Integrin Expression at Baseline, Month 3, and Month 6	Alpha4-integrin expression is the mean fluorescent intensity (MFI), a measure of fluorescence intensity often used to monitor changes in surface antigen modulation in flow cytometry. There is no reference range for this test, which was developed at Biogen Idec.	Month 0 (Baseline), Month 3, and Month 6	No