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.

• Register: EUCTR
• Last refreshed on: 23 May 2012
• Main ID: EUCTR2010-019028-30-GB
• Date of registration: 02/08/2010
• Prospective Registration: No
• Primary sponsor: Novartis Pharma Services AG
• Public 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.
• Scientific 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.
• Date of first enrolment: 30/07/2010
• Target sample size: 120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019028-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: yes Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Finland, France, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Patients eligible for inclusion in this study have to fulfill all of the following criteria: 1. Written informed consent must be obtained before any assessment is performed. 2. Male and female patients aged 18-55 years. 3. Lifetime tetanus vaccination. 4. Patients with relapsing forms of MS, defined by 2005 revised McDonald criteria. 5. Patients with Expanded Disability Status Scale (EDSS) score of 0-6.5. 6. Agree to receive 2010/11 northern hemisphere seasonal influenza vaccine 7. Agree to receive tetanus toxoid booster vaccine
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients fulfilling any of the following criteria are not eligible for inclusion into the study: 1. Patients with a manifestation of MS other than relapsing MS. 2. History of vaccination with 2010/11 northern hemisphere seasonal influenza vaccine or plans to receive outside this study. 3. Laboratory-confirmed influenza disease within 6 months prior to Visit 1. 4. History of vaccination with H1N1 (2009 pandemic swine flu) vaccine or documented confirmed or suspected H1N1 influenza disease within 3 months prior to Day 1. 5. History of tetanus booster vaccination in one year prior to randomization. 6. History of anaphylaxis or serious reaction after administration of any vaccine, or hypersensitivity to eggs, egg protein, chicken feathers, influenza viral protein, neomycin, kanamycin, or any other vaccine component, chemically related substance, or component of the potential packaging materials. 7. Patients who have had an allergic reaction to previous tetanus vaccine 8. Patients with a history of chronic disease of the immune system other than MS or with a known immunodeficiency syndrome. 9. History or presence of malignancy (except for successfully treated basal or squamous cell carcinoma of skin). 10. A known or ‘new’ diagnosis of diabetes mellitus (if screening blood glucose is suspicious for diabetes [=126 mg/dL or =7 mmol/L if fasting; =200 mg/dL or 11.1 mmol/L if random testing] a patient should be further evaluated for diabetes mellitus). 11. Diagnosis of macular edema during Pre-randomization Phase (patients with a history of macular edema will be allowed to enter the study provided that they do not have macular edema at the ophthalmic screening visit). 12. Patients with active systemic bacterial, viral or fungal infections, or known to have Hepatitis B, Hepatitis C infection or to have positive Hepatitis B surface antigen or Hepatitis C antibody tests. 13. Negative for varicella-zoster virus IgG antibodies at Screening. 14. Have received or expect to receive any live or live-attenuated vaccines (including for varicella-zoster virus or measles) within 2 months prior to randomization or during the study. 15. Patients who have received total lymphoid irradiation or bone marrow transplantation. 16. Patients who have been treated with listed medication types 17. Patients with any medically unstable condition, as assessed by the primary treating physician at each site. 18. Patients with any of the listed cardiovascular conditions 19. Patients with any of the following pulmonary conditions: • pulmonary fibrosis; • active tuberculosis. 20. Patients with any of the listed hepatic conditions 21. Patients with any of the listed abnormal laboratory values: 22. Patients with any of the listed neurologic/psychiatric disorders: 23. Participation in any clinical research study evaluating another investigational drug or therapy within 6 months prior to Baseline. 24. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml) 25. Women of child-bearing potential 26. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes 27. Prior participation in a trial with fingolimod. For a detailed descrition of all exclusion criteria, please refer to section 4.2 of the enclosed protocol.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Relapsing forms of multiple sclerosis.
MedDRA version: 12.1 Level: LLT Classification code 10048393 Term: Multiple sclerosis relapse

Intervention(s)

Product Name: FTY720
Product Code: FTY720D
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: fingolimod
CAS Number: 162359-56-0
Current Sponsor code: FTY720
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary variable is the responder rate to the seasonal influenza vaccine at Visit 7. The responder rate is defined as the proportion of 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 (Visit 6) is <1:10 and the post-vaccination measurement is =1:40. • Significant increase: the pre-vaccination antibody titer measurement (Visit 6) is =1:10 and the increase in antibody titer from this to the post-vaccination measurement is =4-fold.

Main Objective: To evaluate the immune response in MS patients treated with fingolimod (compared to placebo) three weeks after a single dose of seasonal influenza vaccine as assessed by the proportion of patients showing seroconversion or showing a significant increase in the HAI antibody titers against at least one of three virus strain antigens after vaccination.

Secondary Objective: • To evaluate the immune response in MS patients treated with fingolimod (compared to placebo) six weeks after a single dose of seasonal influenza vaccine as assessed by the proportion of patients showing seroconversion or showing a significant increase in the HAI antibody titers against at least one of three virus strain antigens after vaccination. • To evaluate the immune response to a single dose of tetanus toxoid (TT) as assessed by the proportion of patients with seroconversion or a significant increase (=4-fold) in antibody titers. • To estimate the inhibition of an immune response to each strain included in the seasonal influenza vaccine as assessed by the relative difference of the geometric mean antibody titer ratio on fingolimod as compared to placebo three and six weeks after a single dose of seasonal influenza vaccine. For a detailed description of the Secondary Objectives, please refer to section 2.2 of the enclosed protocol.

Secondary ID(s)

2010-019028-30-FI

CFTY720D2320