Safety and Immunogenicity of Two Doses of a Tetravalent Influenza Vaccine in Adults Aged 18 Years and Above

Influenza Clinical Trial

Official title:

A Phase II, Randomized, Placebo-controlled, Observer-blind, Multi Center Study on the Safety and Immunogenicity of Novartis Tetravalent Influenza Vaccine (Containing Both Interpandemic Strains and H5N1) in Adults Aged 18 Years and Above

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00620815
• Other study ID #: V101P1
• Secondary ID: 2007-002712-25
• Status: Completed
• Phase: Phase 2
• First received: February 12, 2008
• Last updated: October 7, 2015
• Start date: November 2007
• Est. completion date: December 2008

Study information

• Verified date: October 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial Summary

Evaluate the immune response and reactogenicity of H5N1 vaccination in adults aged 18 years and above (as part of a tetravalent vaccine)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 601
• Est. completion date: December 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Healthy subjects (aged 18 years and above) who have signed an informed consent form

Exclusion Criteria:

• Any acute or chronic illness

• Receipt of seasonal influenza vaccine for the current season 2007/2008

• Known or suspected impairment/alteration of immune function

• Receipt of another vaccine within 3 weeks prior to Visit 1 or planned vaccination within 3 weeks following the last study vaccination

• Any serious disease

• Hypersensitivity to eggs, chicken protein, chicken feathers, influenza viral protein,neomycin or kanamycin or any other component of the study vaccine

• Receipt of blood, blood products or immunoglobulins 3 months prior to vaccination

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Biological:
• MF59-eTIV-H5N1+ placebo /pandemic influenza vaccine
Tetravalent influenza vaccine (MF59-eTIV-H5N1)and placebo on day 1 followed 3-5 weeks later by pandemic influenza vaccine, including serology blood draw at V1+V3.
• Pandemic influenza vaccine + placebo /MF59-eTIV-H5N1
Pandemic influenza vaccine plus placebo on day 1 followed 3-5 weeks later by tetravalent influenza vaccine (MF59-eTIV-H5N1), including serology blood draw at V1+V3.
• Pandemic influenza vaccine + seasonal influenza vaccine /pandemic influenza vaccine
Pandemic influenza vaccine plus seasonal influenza vaccine, 3-5 weeks later pandemic influenza vaccine , including serology blood draw at V1+V3.
• Pandemic influenza vaccine + placebo / MF59-eTIV-H5N1
Pandemic influenza vaccine plus placebo followed 3-5 weeks later by tetravalent influenza vaccine (MF59-eTIV-H5N1), including serology blood draw at V1, V2 and V3.
• Pandemic influenza vaccine + seasonal influenza vaccine / pandemic influenza vaccine
Pandemic influenza vaccine plus seasonal influenza vaccine followed 3-5 weeks later by pandemic influenza vaccine, including serology blood draw at V1, V2 and V3.
• MF59-eTIV-H5N1 + Placebo/pandemic influenza vaccine
Tetravalent influenza vaccine (MF59-eTIV-H5N1)plus placebo followed 3-5 weeks later by pandemic influenza vaccine, including serology blood draw at V1, V2 and V3.

Locations

Country	Name	City	State
Germany	ATRIUM Gesundheitszentrum;	Holzkirchen
Germany	International Medicine & Public Health Dept. of Infect. Diseases	Munich

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Vaccines

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To Demonstrate the Equivalence of Antibody Response Against A/H5N1 Strain Elicited by the Three Different Immunization Schedules on Day 43.	The antibody response was determined by SRH assay. Geometric mean areas (GMAs) and geometric mean ratios (GMRs) in the SRH assay were used to demonstrate the equivalence.; The statistical analysis was done based on the GMRs.	up to day 43	No
Secondary	Number of Subjects (Subjects = 60 Years) With Reported Local Reactions After First Vaccination	Local reactions were collected up to 7 days after 1st vaccinations. All subjects were instructed to complete a diary card to record local reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization. The table represents local reactions after first vaccination in each arm differently.	Up to 7 days after 1st vaccination	Yes
Secondary	Number of Subjects (Subjects =60 Years) With Reported Local Reactions After Second Vaccination	Local reactions were collected up to 7 days after 1st vaccinations. All subjects were instructed to complete a diary card to record local reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization.	Up to 7 days after 2nd vaccination	Yes
Secondary	Number of Subjects (Subjects = 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations.	Systemic reactions were collected upto 7 days after 1st and 2nd vaccinations. All subjects were instructed to complete a diary card to record systemic reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization.	7 days after 1st and 2nd vaccinations each	Yes
Secondary	Percentages of Subjects Achieving Seroconversion/Significant Increase in Antibody Titre/ Area as Measured by SRH and (HI) and at Least 4 Fold Rise in Titres by Micro-neutralization (MN) Assay-H5N1 Strain	Measurement of immunogenicity in terms of significant increase in antibody titer and Seroconversion.; Significant increase in antibody titer is defined as at least a four-fold increase from non-negative pre-vaccination serum (= 10) for HI or a 50% increase in area for SRH.; Seroconversion is defined as negative pre-vaccination serum / post-vaccination titer =40 for HI (area =25 mm2 for SRH)	up to day 43	No
Secondary	Percentages of Subjects Achieving HI/MN = 1:40 and SRH Area = 25^mm2	Measurement of immunogenicity in terms of percentage of subjects achieving a titre = 40/area = 25mm^2 after immunization as determined by HI (Haemagglutination Inhibition), MN(Microneutralization) and SRH assay.	Up to 43 days	No
Secondary	Antibody Response Determined by HI and MN Assay.	Measurement of immunogenicity in terms of Geometric mean titers (GMTs) as determined by HI and MN assay.	Up to 43 days	No
Secondary	Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination.	The Cell Mediated Immunity (CMI) response was evaluated in a randomly selected subgroup of approximately 92 subjects from all the vaccine groups out of a total of 601 enrolled subjects.; Frequency of circulating memory B cells (MBC), capable of differentiating in vitro into cell secreting IgG (Immunoglobulin G) antibodies specific for H5N1 (the subunit from A/Vietnam/1194/2004) or for H1N1 (the subunit from A/Solomon Island/3/2006) were determined by an ELISA-coupled limiting dilution assay.The frequency of H5N1-IgG MBC and H1N1-IgG MBC was expressed as percentages (%) of total IgG producing MBC	Three weeks after first vaccination (day 22) and three weeks after second vaccination (day 43)	No
Secondary	Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit	Frequency and functionality of vaccine antigen-specific CD4+ T cells was assessed in peripheral blood (PBMC) taken at days 1, 22 and 43 after in vitro stimulation with: Library of 70 peptides spanning the whole H5 A/Vietnam/1194/2004 protein (H5 pool of 70 Vietnam) H5N1 subunit from A/Vietnam/1194/2004 (H5N1 Vietnam) H3N2 subunit from A/ Wisconsin/67/2005 (H3N2 Wisconsin) H1N1 subunit from A/Solomon Islands/3/2006 (H1N1 Solomon Islands) Polyclonal stimulus agonistic aCD3 mAb (aCD3); The change in frequency of T-cells was measured.	Three weeks after 1st vaccination (day 22) and three weeks after 2nd vaccination (day 43)	No