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

• ClinicalTrials.gov Identifier: NCT01199861
• Recruitment Status: Completed
• First Posted: September 13, 2010
• Results First Posted: June 19, 2012
• Last Update Posted: June 19, 2012
• Sponsor: Novartis
• Information provided by (Responsible Party): Novartis

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.

Condition or disease	Intervention/treatment	Phase
Relapsing Multiple Sclerosis	Drug: Fingolimod; Drug: Placebo; Biological: Seasonal influenza vaccine; Biological: Tetanus toxoid vaccine	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 138 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, 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)
• Study Start Date: August 2010
• Actual Primary Completion Date: May 2011
• Actual Study Completion Date: May 2011

Arms and Interventions

Arm	Intervention/treatment
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)

Outcome Measures

Primary Outcome Measures :

1. Immune Response 3 Weeks After Seasonal Influenza Vaccination [ Time Frame: Week 6 (pre-vaccination) and 3 weeks after vaccination (Study week 9) ]

   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 :

1. Immune Response 6 Weeks After Seasonal Influenza Vaccination [ Time Frame: Week 6 (pre-vaccination) and 6 weeks after vaccination (Study week 12). ]

   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.
2. Immune Response 3 Weeks After Tetanus Toxoid Booster [ Time Frame: Week 6 (pre-vaccination) and 3 weeks after vaccination (Study Week 9) ]

   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.
3. Immune Response 6 Weeks After Tetanus Toxoid Booster [ Time Frame: Week 6 (pre-vaccination) and 6 weeks after vaccination (Study Week 12) ]

   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.
4. 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). ]
   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.
5. 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). ]
   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.
6. 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). ]

   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• 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

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, 28029

Novartis Investigative Site

Madrid, Spain, 28040

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

• Responsible Party: Novartis
• ClinicalTrials.gov Identifier: NCT01199861
• Other Study ID Numbers: CFTY720D2320; 2010-019028-30 ( EudraCT Number )
• First Posted: September 13, 2010
• Results First Posted: June 19, 2012
• Last Update Posted: June 19, 2012
• Last Verified: May 2012

Keywords provided by Novartis:

Relapsing multiple sclerosis; MS; Immune response

Additional relevant MeSH terms:

Multiple Sclerosis; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Vaccines; Fingolimod Hydrochloride; Immunologic Factors; Physiological Effects of Drugs; Sphingosine 1 Phosphate Receptor Modulators; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents