Multiple SclerosisPhase 4NCT00536120

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

A Phase 4 study testing BG00002 (natalizumab), keyhole limpet hemocyanin (KLH) and tetanus diphtheria toxoid vaccine (Td) in people with Multiple Sclerosis, run by Biogen at 10 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Multiple Sclerosis
What is being tested?: BG00002 (natalizumab), keyhole limpet hemocyanin (KLH) and tetanus diphtheria toxoid vaccine (Td)
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 60 participants
Where: 10 sitesUnited States
Study dates: Jan 2008to Dec 2009
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

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:

Show all 27Show fewer

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

Who cannot join

None listed.

Trial locations and contacts

10 sites in 1 country.

City, postcode or hospital

10 sites in 1 country

United States10 sites

Research Site
Centennial, Colorado, 80112
Research Site 4
Charleston, West Virginia, 25301
Research Site 3
Charlotte, North Carolina, 28207
Research Site
Dallas, Texas, 75214
Research site
Farmington Hills, Michigan, 48334
Research Site
Franklin, Tennessee, 37064
Research Site 1
Fullerton, California, 92835
Research Site 5
Oklahoma City, Oklahoma, 73130
Research Site
Patchogue, New York, 11772
Research Site 2
Seattle, Washington, 98122

Other trials in United States

About this study

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

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.

Conditions: Multiple Sclerosis
Being tested: BG00002 (natalizumab), keyhole limpet hemocyanin (KLH), tetanus diphtheria toxoid vaccine (Td)
Keywords: MS, Multiple sclerosis, Relapsing forms of Multiple Sclerosis
Medical subject headings: Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BG00002 (natalizumab)Biological
Also called Tysabri
keyhole limpet hemocyanin (KLH)Biological
Also called Immucothel
KLH 1 mg administered subcutaneously (SC) in accordance with the Immucothel investigator's brochure.
tetanus diphtheria toxoid vaccine (Td)Biological
Td administered in accordance with the manufacturer's prescribing information.

Study groups in NCT00536120
Study group	Role	What they receive
Tysabri Plus Vaccinations	Experimental	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. Receives: Biological: BG00002 (natalizumab); Biological: keyhole limpet hemocyanin (KLH); Biological: tetanus diphtheria toxoid vaccine (Td)
Vaccinations Only	Other	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. Receives: Biological: keyhole limpet hemocyanin (KLH); Biological: tetanus diphtheria toxoid vaccine (Td)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 28 days after immunization (Day 28 for Vaccinations Only Group/Day 196 for Tysabri Plus Vaccinations Group)
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.
Measured: 28 days after immunization (Day 28 for Vaccinations Only Group/Day 196 for Tysabri Plus Vaccinations Group)

Secondary outcomes (4)

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).
Measured: Month 0 (Baseline), Month 3
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).
Measured: Month 0 (Baseline), Month 6
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.
Measured: Month 0 (Baseline), Month 3, and Month 6
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.
Measured: Month 0 (Baseline), Month 3, and Month 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2008Dec 2009

First posted27 Sep 2007 (estimated)
Study startJan 2008
Primary completionNov 2009
Study completionDec 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Multiple SclerosisStudies of the same condition, open and under way.
More trials run by BiogenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 60 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00536120
Sponsor's protocol ID: 101MS404
Status last verified: Dec 2016
First submitted: 25 Sep 2007
Last updated: 15 Feb 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 24731783

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 15 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00536120
Acronym / sponsor ID: 101MS404
Conditions: Multiple Sclerosis
Keywords: MS, Multiple sclerosis, Relapsing forms of Multiple Sclerosis
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 60 participants (actual)
Lead sponsor: BiogenIndustry (pharma, biotech, devices)
Study start: Jan 2008
Primary completion: Nov 2009 (actual)
Study completion: Dec 2009 (actual)
First posted: 27 Sep 2007 (estimated)
Results: Posted 29 Jul 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Tysabri Plus Vaccinations	Experimental	Biological: BG00002 (natalizumab), Biological: keyhole limpet hemocyanin (KLH), Biological: tetanus diphtheria toxoid vaccine (Td)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.
Vaccinations Only	Other	Biological: keyhole limpet hemocyanin (KLH), Biological: tetanus diphtheria toxoid vaccine (Td)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.

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (27 listed)

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

Key exclusion criteria (0 listed)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BG00002 (natalizumab)Also: Tysabri	Biological	Tysabri Plus Vaccinations
keyhole limpet hemocyanin (KLH)Also: ImmucothelKLH 1 mg administered subcutaneously (SC) in accordance with the Immucothel investigator's brochure.	Biological	Tysabri Plus Vaccinations, Vaccinations Only
tetanus diphtheria toxoid vaccine (Td)Td administered in accordance with the manufacturer's prescribing information.	Biological	Tysabri Plus Vaccinations, Vaccinations Only

Primary outcome

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)
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)
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.

4 secondary outcomes

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
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
Mean Alpha4-Integrin Saturation at Baseline, Month 3, and Month 6
Time frame: Month 0 (Baseline), Month 3, and Month 6
Mean Alpha4-Integrin Expression at Baseline, Month 3, and Month 6
Time frame: Month 0 (Baseline), Month 3, and Month 6

Results and safety

Results posted to the registry on 29 Jul 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tysabri Plus Vaccinations	30	24
Vaccinations Only	30	27

Primary outcome: 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). Number. Unit: percentage of participants

Measure	Tysabri Plus Vaccinations n = 19	Vaccinations Only n = 23
Value	89	83

Population analysed: Participants with an assessment at Day 28. No imputation methods were used in the primary analyses.

Primary outcome: 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). Number. Unit: percentage of participants

Measure	Tysabri Plus Vaccinations n = 16	Vaccinations Only n = 24
Value	94	100

Population analysed: Participants with an assessment at Day 28 and a pre-immunization antibody value ≤ 3.5 IU/mL. No imputation methods were used in the primary analyses.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected from dosing at the Baseline Visit (Month 0) until the participant's End of Study Visit (Month 8). Serious adverse events were collected from screening until 12 weeks following the participant's last dose of Tysabri.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tysabri Plus Vaccinations	3 of 30 (10%)	25 of 30 (83.3%)	Not reported
Vaccinations Only	2 of 30 (6.7%)	19 of 30 (63.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 24731783Kaufman 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Biogen

10 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jul 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00536120, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2017.