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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biogen Idec
ClinicalTrials.gov Identifier:
NCT00536120
First received: September 25, 2007
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis
Biological: BG00002 (natalizumab)
Biological: keyhole limpet hemocyanin (KLH)
Biological: tetanus diphtheria toxoid vaccine (Td)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Biogen Idec:

Primary Outcome Measures:
  • Percentage of Keyhole Limpet Hemocyanin (KLH) Responders at Day 28 Post-Vaccination [ Time Frame: 28 days after immunization (Day 28 for Vaccinations Only Group/Day 196 for Tysabri Plus Vaccinations Group) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Tetanus Diphtheria Toxoid (Td) Responders at Day 28 Post-Vaccination [ Time Frame: 28 days after immunization (Day 28 for Vaccinations Only Group/Day 196 for Tysabri Plus Vaccinations Group) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mean Percentage Change From Baseline in Circulating Lymphocyte Subsets CD3+, CD4+, CD8+, CD19+, and CD56+ at Month 3 of Tysabri Therapy [ Time Frame: Month 0 (Baseline), Month 3 ] [ Designated as safety issue: No ]
    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).

  • Mean Percentage Change From Baseline in Circulating Lymphocyte Subsets CD3+, CD4+, CD8+, CD19+, and CD56+ at Month 6 of Tysabri Therapy [ Time Frame: Month 0 (Baseline), Month 6 ] [ Designated as safety issue: No ]
    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).

  • Mean Alpha4-Integrin Saturation at Baseline, Month 3, and Month 6 [ Time Frame: Month 0 (Baseline), Month 3, and Month 6 ] [ Designated as safety issue: No ]
    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.

  • Mean Alpha4-Integrin Expression at Baseline, Month 3, and Month 6 [ Time Frame: Month 0 (Baseline), Month 3, and Month 6 ] [ Designated as safety issue: No ]
    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.


Enrollment: 60
Study Start Date: January 2008
Study Completion Date: December 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tysabri Plus Vaccinations
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.
Biological: BG00002 (natalizumab)
Other Name: Tysabri
Biological: keyhole limpet hemocyanin (KLH)
KLH 1 mg administered subcutaneously (SC) in accordance with the Immucothel investigator's brochure.
Other Name: Immucothel
Biological: tetanus diphtheria toxoid vaccine (Td)
Td administered in accordance with the manufacturer's prescribing information.
Vaccinations Only
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.
Biological: keyhole limpet hemocyanin (KLH)
KLH 1 mg administered subcutaneously (SC) in accordance with the Immucothel investigator's brochure.
Other Name: Immucothel
Biological: tetanus diphtheria toxoid vaccine (Td)
Td administered in accordance with the manufacturer's prescribing information.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00536120

Locations
United States, California
Research Site 1
Fullerton, California, United States, 92835
United States, Colorado
Research Site
Centennial, Colorado, United States, 80112
United States, Michigan
Research site
Farmington Hills, Michigan, United States, 48334
United States, New York
Research Site
Patchogue, New York, United States, 11772
United States, North Carolina
Research Site 3
Charlotte, North Carolina, United States, 28207
United States, Oklahoma
Research Site 5
Oklahoma City, Oklahoma, United States, 73130
United States, Tennessee
Research Site
Franklin, Tennessee, United States, 37064
United States, Texas
Research Site
Dallas, Texas, United States, 75214
United States, Washington
Research Site 2
Seattle, Washington, United States, 98122
United States, West Virginia
Research Site 4
Charleston, West Virginia, United States, 25301
Sponsors and Collaborators
Biogen Idec
Investigators
Study Director: Medical Director Biogen Idec
  More Information

No publications provided

Responsible Party: Biogen Idec
ClinicalTrials.gov Identifier: NCT00536120     History of Changes
Other Study ID Numbers: 101MS404
Study First Received: September 25, 2007
Results First Received: March 17, 2011
Last Updated: March 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Biogen Idec:
MS
Multiple sclerosis
Relapsing forms of Multiple Sclerosis

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Keyhole-limpet hemocyanin
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014