The Effects of TYSABRI Treatment on Vaccination Response and Lymphocyte Subsets in Subjects With Relapsing Forms of Multiple Sclerosis - Full Text View

Sponsor:	Biogen Idec
Information provided by:	Biogen Idec
ClinicalTrials.gov Identifier:	NCT00536120

Purpose

Although TYSABRI has been studied in clinical trials, and has been approved by the FDA for the treatment of MS, no information is available on the effects of vaccination (immunization against disease, such as measles or tetanus) in patients who receive TYSABRI. This study is designed to determine the effects of TYSABRI treatment on vaccinations in people. In order to do this, some people will receive 6 doses of TYSABRI before being vaccinated, and some people will receive only the vaccinations (no treatment for MS will be given for approximately 3 months).

Condition	Intervention	Phase
Multiple Sclerosis	Biological: TYSABRI (natalizumab)	Phase IV

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:

MedlinePlus related topics: Multiple Sclerosis Tetanus

Drug Information available for: Natalizumab

U.S. FDA Resources

Further study details as provided by Biogen Idec:

Primary Outcome Measures:

Proportion of KLH Responders at Day 28 [ Time Frame: 28 days after immunization ] [ Designated as safety issue: Yes ]
KLH responders were defined as those participants who had at least a two-fold increase over pre-immunization level of anti-KLH antibodies in their blood at 28 days after vaccination with KLH.
Proportion of Tetanus Responders at Day 28 [ Time Frame: 28 days after immunization ] [ Designated as safety issue: Yes ]
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.

Enrollment:	60
Study Start Date:	January 2008
Study Completion Date:	January 2010
Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Group 1 subjects will receive 9 monthly doses of TYSABRI 300 mg IV, and will then receive vaccinations with neoantigen and recall antigen at specified timepoints following the 7th dose.	Biological: TYSABRI (natalizumab) TYSABRI 300 mg IV once every 4 weeks,to be administered over 1 hour, with a 1-hour observation period to follow the infusion
No Intervention: 2 Group 2 subjects will receive only vaccinations with neoantigen and recall antigen at specified timepoints. They will not receive any treatment for their MS.

Detailed Description:

The purpose of the study is to see whether TYSABRI affects the ability of your immune system to respond to a vaccination that you have had before (tetanus), and to a new vaccination, keyhole limpet hemocyanin (KLH), which most people have not had before. KLH is often used to study the immune system. This study will measure levels of antibodies that the body makes to tetanus and KLH after each vaccination. This study will also see whether TYSABRI affects the immune cells in the blood that fight infection (white cells and lymphocytes).

Subjects will be randomly assigned to a treatment group. This is done so that each group has a similar number and mix of people. Each group will have 23 people.

Each subject will have an equal chance of being placed in either group.

Group 1 will receive TYSABRI and vaccinations.
Group 2 will receive vaccinations only (no MS treatment will be given for approximately 3 months).

This is an open-label study, which means that you and your doctor will know what treatment group you are assigned to. Both Group 1 and Group 2 will receive the same vaccinations:

Tetanus (1 vaccination)
KLH (3 vaccinations, 14 days apart)

Subjects assigned to Group 1 will come to the clinic for about 10 clinic visits over a 9-month period. Additional clinic visits may be required if neurological symptoms worsen.

Subjects assigned to Group 2 will come to the clinic for 4 clinic visits over a 3-month period. Group 2 subjects will receive vaccinations only, and will not receive treatment for their MS during this study.

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-diptheria vaccine or KLH or any other administered vaccinations or their components (such as thimerosol)
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 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 IV or 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

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

More Information

No publications provided

Responsible Party:	Biogen Idec Medical Director, 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:	June 30, 2011
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:

Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases

Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on February 09, 2012