Effect of Treatment With Fingolimod on the Immune Response Following Seasonal Flu Vaccination and Tetanus Booster Injection in Patients With Relapsing Multiple Sclerosis (MS)

Study Overview
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Brief Summary
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This study will evaluate the effect of treatment with fingolimod on the immune response following seasonal influenza vaccination and tetanus booster injection in patients with relapsing MS.

Official Title
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A 3-month Blinded, Randomized, Multicenter, Placebo-controlled Study to Evaluate the Effect of Treatment With Fingolimod on the Immune Response Following Seasonal Influenza Vaccination and Tetanus Toxoid Booster Injection in Patients With Relapsing Forms of Multiple Sclerosis (MS)

Conditions
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Relapsing Multiple Sclerosis

Intervention / Treatment
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* Drug: Fingolimod
* Drug: Placebo
* Biological: Seasonal influenza vaccine
* Biological: Tetanus toxoid vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have relapsing MS Must have lifetime tetanus vaccination Agree to receive 2010/2011 seasonal influenza vaccine and tetanus toxoid booster injection Exclusion Criteria: Patients with a type of MS that is not relapsing Patients with history of chronic immune disease Certain cancers Diabetic patients with certain eye disorders Patients who are on certain immunosuppressive medications or heart medications Patients with certain heart conditions Patients with certain lung conditions Patients who have already received the 2010/2011 seasonal influenza vaccine Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fingolimod<br>Participants received Fingolimod 0.5 mg capsules orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination. | Drug: Fingolimod<br>* Fingolimod 0.5 mg capsules for oral administration.<br>* Other names: FTY720;Biological: Seasonal influenza vaccine<br>* Commercially available injectable influenza vaccine for the 2010/11 influenza season.<br>* Other names: Agrippal (TM);Biological: Tetanus toxoid vaccine<br>* Commercially available tetanus toxoid vaccine booster injection.<br>* Other names: Tetanol (TM);|
| Placebo Comparator: Placebo<br>Participants received placebo tablets orally once daily for 12 weeks. At Week 6 of study treatment participants received a seasonal influenza vaccination and a tetanus booster vaccination. | Drug: Placebo<br>* Matching placebo capsules for oral administration.<br>Biological: Seasonal influenza vaccine<br>* Commercially available injectable influenza vaccine for the 2010/11 influenza season.<br>* Other names: Agrippal (TM);Biological: Tetanus toxoid vaccine<br>* Commercially available tetanus toxoid vaccine booster injection.<br>* Other names: Tetanol (TM);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune Response 3 Weeks After Seasonal Influenza Vaccination | Percentage of participants who responded to treatment with the seasonal influenza vaccine 3 weeks after vaccination. Response was defined as patients fulfilling one of the following criteria for at least one of the three strains contained in the seasonal influenza vaccine: Seroconversion: The pre-vaccination antibody titer measurement was <1:10 and the post-vaccination measurement is ≥1:40. Significant increase in antibody titer: The pre-vaccination antibody titer measurement was ≥1:10 and the increase in antibody titer from this to the post-vaccination measurement is ≥ 4-fold. | Week 6 (pre-vaccination) and 3 weeks after vaccination (Study week 9) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune Response 6 Weeks After Seasonal Influenza Vaccination | Percentage of participants who responded to treatment with the seasonal influenza vaccine 6 weeks after vaccination. Response was defined as patients fulfilling one of the following criteria for at least one of the three strains contained in the seasonal influenza vaccine: Seroconversion: The pre-vaccination antibody titer measurement was <1:10 and the post-vaccination measurement is ≥1:40. Significant increase in antibody titer: The pre-vaccination antibody titer measurement was ≥1:10 and the increase in antibody titer from this to the post-vaccination measurement is ≥ 4-fold. | Week 6 (pre-vaccination) and 6 weeks after vaccination (Study week 12). | 
| Immune Response 3 Weeks After Tetanus Toxoid Booster | Percentage of participants with an immune response to a single dose of tetanus toxoid three weeks after vaccination. A patient was considered a responder to tetanus toxoid booster vaccination if one of the following criteria was met: Seroconversion: The pre-vaccination antibody titer measurement was <0.1 IU/ml and the post-vaccination measurement was ≥0.4 IU/ml. Significant increase: The pre-vaccination antibody titer measurement was ≥0.1 IU/ml and the increase in antibody titer from this to the post-vaccination measurement was ≥4- fold. | Week 6 (pre-vaccination) and 3 weeks after vaccination (Study Week 9) | 
| Immune Response 6 Weeks After Tetanus Toxoid Booster | Percentage of participants with an immune response to a single dose of tetanus toxoid six weeks after vaccination. A patient was considered a responder to tetanus toxoid booster vaccination if one of the following criteria was met: Seroconversion: The pre-vaccination antibody titer measurement was <0.1 IU/ml and the post-vaccination measurement was ≥0.4 IU/ml. Significant increase: The pre-vaccination antibody titer measurement was ≥0.1 IU/ml and the increase in antibody titer from this to the post-vaccination measurement was ≥4- fold. | Week 6 (pre-vaccination) and 6 weeks after vaccination (Study Week 12) | 
| Change From Baseline in Seasonal Influenza Vaccine Antibody-titer 3 Weeks After Vaccination | Change from Baseline was expressed by the ratio of post-vaccination to pre-vaccination antibody titer for each of the three strains included in the seasonal influenza vaccine. Inhibition of an immune response to each strain included in the seasonal influenza vaccine was assessed by the relative difference of the geometric mean antibody titer ratio on fingolimod as compared to placebo three weeks after a single dose of seasonal influenza vaccine. | Pre-vaccination (Week 6) and 3 weeks after vaccination (Study Week 9). | 
| Change From Baseline in Seasonal Influenza Vaccine Antibody-titer 6 Weeks After Vaccination | Change from Baseline was expressed by the ratio of post-vaccination to pre-vaccination antibody titer for each of the three strains included in the seasonal influenza vaccine. Inhibition of an immune response to each strain included in the seasonal influenza vaccine was assessed by the relative difference of the geometric mean antibody titer ratio on fingolimod as compared to placebo six weeks after a single dose of seasonal influenza vaccine. | Pre-vaccination (Week 6) and 6 weeks after vaccination (Study Week 12). | 
| Number of Participants With Adverse Events (AEs) | Relationship to study drug was determined by the investigator (suspected/not suspected). A serious AE is defined as an event which fulfills one of the following criteria: is fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; requires inpatient hospitalization or prolongation of existing hospitalization; is medically significant, i.e., jeopardizes the patient or may require intervention to prevent one of the outcomes listed above. | From first dose of study drug until 45 days after the last dose of study drug (130 days). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsing multiple sclerosis, MS, Immune response