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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis
ClinicalTrials.gov Identifier:
NCT01199861
First received: September 9, 2010
Last updated: May 15, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Relapsing Multiple Sclerosis
Drug: Fingolimod
Drug: Placebo
Biological: Seasonal influenza vaccine
Biological: Tetanus toxoid vaccine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Immune Response 3 Weeks After Seasonal Influenza Vaccination [ Time Frame: Week 6 (pre-vaccination) and 3 weeks after vaccination (Study week 9) ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: Week 6 (pre-vaccination) and 6 weeks after vaccination (Study week 12). ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: Week 6 (pre-vaccination) and 3 weeks after vaccination (Study Week 9) ] [ Designated as safety issue: Yes ]

    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:

    1. Seroconversion: The pre-vaccination antibody titer measurement was <0.1 IU/ml and the post-vaccination measurement was ≥0.4 IU/ml.
    2. 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 [ Time Frame: Week 6 (pre-vaccination) and 6 weeks after vaccination (Study Week 12) ] [ Designated as safety issue: Yes ]

    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:

    1. Seroconversion: The pre-vaccination antibody titer measurement was <0.1 IU/ml and the post-vaccination measurement was ≥0.4 IU/ml.
    2. 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 [ Time Frame: Pre-vaccination (Week 6) and 3 weeks after vaccination (Study Week 9). ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Pre-vaccination (Week 6) and 6 weeks after vaccination (Study Week 12). ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: From first dose of study drug until 45 days after the last dose of study drug (130 days). ] [ Designated as safety issue: Yes ]

    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.


Enrollment: 138
Study Start Date: August 2010
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fingolimod
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
Fingolimod 0.5 mg capsules for oral administration.
Other Name: FTY720
Biological: Seasonal influenza vaccine
Commercially available injectable influenza vaccine for the 2010/11 influenza season.
Other Name: Agrippal (TM)
Biological: Tetanus toxoid vaccine
Commercially available tetanus toxoid vaccine booster injection.
Other Name: Tetanol (TM)
Placebo Comparator: Placebo
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
Matching placebo capsules for oral administration.
Biological: Seasonal influenza vaccine
Commercially available injectable influenza vaccine for the 2010/11 influenza season.
Other Name: Agrippal (TM)
Biological: Tetanus toxoid vaccine
Commercially available tetanus toxoid vaccine booster injection.
Other Name: Tetanol (TM)

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  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: NCT01199861

Locations
Belgium
Novartis Investigative Site
Aalst, Belgium, 9300
Novartis Investigative Site
Bruxelles, Belgium, 1200
Novartis Investigative Site
Leuven, Belgium, 3000
Novartis Investigative Site
Liege, Belgium, 4000
Novartis Investigative Site
Wilrijk, Belgium, 2610
Canada, Ontario
Novartis Investigative Site
Nepean, Ontario, Canada, K2G 6E2
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H3A 2B4
Canada
Novartis Investigative Site
Sherbrooke, Canada, JiH 5N4
Finland
Novartis Investigative Site
Seinajoki, Finland, 60220
Novartis Investigative Site
Turku, Finland, 20100
France
Novartis Investigative Site
Caen, France, 14033
Novartis Investigative Site
Rennes, France, 35043
Novartis Investigative Site
St Herblain, France, 44800
Novartis Investigative Site
Toulouse, France, 31059
Guatemala
Novartis Investigative Site
Guatemala City, Guatemala, 01010
Novartis Investigative Site
Guatemala City, Guatemala, 01014
Poland
Novartis Investigative Site
Katowice, Poland, 40-594
Novartis Investigative Site
Lodz, Poland, 90-153
Spain
Novartis Investigative Site
Madrid, Spain, 28040
Novartis Investigative Site
Madrid, Spain, 28029
Novartis Investigative Site
Sevilla, Spain, 41009
Novartis Investigative Site
Valencia, Spain, 46009
Switzerland
Novartis Investigational Site
Basel, Switzerland, 4031
United Kingdom
Novartis Investigative Site
Nottingham, United Kingdom, NG7 2UH
Novartis Investigative Site
Stoke-on-Trent, United Kingdom, ST4 7LN
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT01199861     History of Changes
Other Study ID Numbers: CFTY720D2320, 2010-019028-30
Study First Received: September 9, 2010
Results First Received: May 15, 2012
Last Updated: May 15, 2012
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
Finland: Finnish Medicines Agency
FRANCE: agence francaise de sécurité sanitaire des produits des santé
GUATEMALA: Departamento de Regulación, y Control de Productos Farmacéuticos y Afines
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Relapsing multiple sclerosis
MS
Immune response

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes
Fingolimod
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014