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

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Primary Purpose

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Fingolimod

Placebo

Seasonal influenza vaccine

Tetanus toxoid vaccine

About this trial

This is an interventional treatment trial for Relapsing Multiple Sclerosis focused on measuring Relapsing multiple sclerosis, MS, Immune response

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Fingolimod

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT01199861

First Posted

September 9, 2010

Last Updated

May 15, 2012

Sponsor

Novartis

1. Study Identification

Unique Protocol Identification Number

NCT01199861

Brief Title

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

Official Title

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)

Study Type

Interventional

2. Study Status

Record Verification Date

May 2012

Overall Recruitment Status

Completed

Study Start Date

August 2010 (undefined)

Primary Completion Date

May 2011 (Actual)

Study Completion Date

May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis

4. Oversight

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Relapsing Multiple Sclerosis

Keywords

Relapsing multiple sclerosis, MS, Immune response

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

138 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Fingolimod

Arm Type

Experimental

Arm Description

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.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Fingolimod

Other Intervention Name(s)

FTY720

Intervention Description

Fingolimod 0.5 mg capsules for oral administration.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Matching placebo capsules for oral administration.

Intervention Type

Biological

Intervention Name(s)

Seasonal influenza vaccine

Other Intervention Name(s)

Agrippal (TM)

Intervention Description

Commercially available injectable influenza vaccine for the 2010/11 influenza season.

Intervention Type

Biological

Intervention Name(s)

Tetanus toxoid vaccine

Other Intervention Name(s)

Tetanol (TM)

Intervention Description

Commercially available tetanus toxoid vaccine booster injection.

Primary Outcome Measure Information:

Title

Immune Response 3 Weeks After Seasonal Influenza Vaccination

Description

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.

Time Frame

Week 6 (pre-vaccination) and 3 weeks after vaccination (Study week 9)

Secondary Outcome Measure Information:

Title

Immune Response 6 Weeks After Seasonal Influenza Vaccination

Description

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.

Time Frame

Week 6 (pre-vaccination) and 6 weeks after vaccination (Study week 12).

Title

Immune Response 3 Weeks After Tetanus Toxoid Booster

Description

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.

Time Frame

Week 6 (pre-vaccination) and 3 weeks after vaccination (Study Week 9)

Title

Immune Response 6 Weeks After Tetanus Toxoid Booster

Description

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.

Time Frame

Week 6 (pre-vaccination) and 6 weeks after vaccination (Study Week 12)

Title

Change From Baseline in Seasonal Influenza Vaccine Antibody-titer 3 Weeks After Vaccination

Description

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.

Time Frame

Pre-vaccination (Week 6) and 3 weeks after vaccination (Study Week 9).

Title

Change From Baseline in Seasonal Influenza Vaccine Antibody-titer 6 Weeks After Vaccination

Description

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.

Time Frame

Pre-vaccination (Week 6) and 6 weeks after vaccination (Study Week 12).

Title

Number of Participants With Adverse Events (AEs)

Description

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.

Time Frame

From first dose of study drug until 45 days after the last dose of study drug (130 days).

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Aalst

ZIP/Postal Code

9300

Country

Belgium

Facility Name

Novartis Investigative Site

City

Bruxelles

ZIP/Postal Code

1200

Country

Belgium

Facility Name

Novartis Investigative Site

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Novartis Investigative Site

City

Liege

ZIP/Postal Code

4000

Country

Belgium

Facility Name

Novartis Investigative Site

City

Wilrijk

ZIP/Postal Code

2610

Country

Belgium

Facility Name

Novartis Investigative Site

City

Nepean

State/Province

Ontario

ZIP/Postal Code

K2G 6E2

Country

Canada

Facility Name

Novartis Investigative Site

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H3A 2B4

Country

Canada

Facility Name

Novartis Investigative Site

City

Sherbrooke

ZIP/Postal Code

JiH 5N4

Country

Canada

Facility Name

Novartis Investigative Site

City

Seinajoki

ZIP/Postal Code

60220

Country

Finland

Facility Name

Novartis Investigative Site

City

Turku

ZIP/Postal Code

20100

Country

Finland

Facility Name

Novartis Investigative Site

City

Caen

ZIP/Postal Code

14033

Country

France

Facility Name

Novartis Investigative Site

City

Rennes

ZIP/Postal Code

35043

Country

France

Facility Name

Novartis Investigative Site

City

St Herblain

ZIP/Postal Code

44800

Country

France

Facility Name

Novartis Investigative Site

City

Toulouse

ZIP/Postal Code

31059

Country

France

Facility Name

Novartis Investigative Site

City

Guatemala City

ZIP/Postal Code

01010

Country

Guatemala

Facility Name

Novartis Investigative Site

City

Guatemala City

ZIP/Postal Code

01014

Country

Guatemala

Facility Name

Novartis Investigative Site

City

Katowice

ZIP/Postal Code

40-594

Country

Poland

Facility Name

Novartis Investigative Site

City

Lodz

ZIP/Postal Code

90-153

Country

Poland

Facility Name

Novartis Investigative Site

City

Madrid

ZIP/Postal Code

28029

Country

Spain

Facility Name

Novartis Investigative Site

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

Novartis Investigative Site

City

Sevilla

ZIP/Postal Code

41009

Country

Spain

Facility Name

Novartis Investigative Site

City

Valencia

ZIP/Postal Code

46009

Country

Spain

Facility Name

Novartis Investigational Site

City

Basel

ZIP/Postal Code

4031

Country

Switzerland

Facility Name

Novartis Investigative Site

City

Nottingham

ZIP/Postal Code

NG7 2UH

Country

United Kingdom

Facility Name

Novartis Investigative Site

City

Stoke-on-Trent

ZIP/Postal Code

ST4 7LN

Country

United Kingdom

Relapsing Multiple Sclerosis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial