A Phase III, Randomized, Controlled, Observer-blind, Multicenter Study to Evaluate the Safety, Tolerability and Immunogenicity of Two Doses of a Monovalent A/H5N1 Influenza Vaccine Adjuvanted With MF59 (Fluad-H5N1) in Adult and Elderly Subjects

Novartis2 sites in 2 countries3,647 target enrollmentOctober 2008

ConditionsPandemic Influenza Disease

Overview

Phase: Phase 3
Intervention: Not specified
Conditions: Pandemic Influenza Disease
Sponsor: Novartis
Enrollment: 3647
Locations: 2
Primary Endpoint: Number of Subjects With at Least One Reactogenicity Sign After Two Doses of the Adjuvanted Pandemic Influenza Vaccine.
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

The present study, phase III, randomized, controlled, observer-blind, multicenter study, will evaluate safety, tolerability and immunogenicity of two doses of an adjuvanted monovalent influenza vaccine compared with an adjuvanted interpandemic trivalent influenza vaccine in a population of healthy adult and elderly subjects.

Registry

clinicaltrials.gov

Start Date

October 2008

End Date

November 2009

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Novartis

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subjects 18 years of age and older who were mentally competent and who had signed an informed consent form after having received a detailed explanation of the study protocol;
•In good health as determined by:
•medical history,
•physical examination,
•clinical judgment of the Investigator;
•Able to understand and comply with all study procedures and to complete study diaries, could be contacted, and were available for study visits;

Exclusion Criteria

•Receipt of another investigational agent within 4 weeks;
•Laboratory-confirmed influenza disease within 6 months prior to Visit 1;
•Receipt of influenza vaccination for current season 2008/2009;
•Experienced any acute disease or infection requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis was acceptable) within the past 7 days;
•Experienced fever (defined as axillary temperature ≥38.0°C) within 7 days prior to Visit 1;
•Pregnant or breastfeeding;
•Females of childbearing potential who were sexually active and had not used or did not plan or refused to use an acceptable method of birth control during the active phase of the study (at least up to three weeks after last vaccine injection);
•Any serious disease, such as: cancer, autoimmune disease (including rheumatoid arthritis); diabetes mellitus type I and type II; diabetes relating to genetic defects/syndromes, diseases of the exocrine pancreas or infections; advanced arteriosclerotic disease; severe chronic obstructive pulmonary disease (COPD), i.e. GOLD stages 3 and 4; acute or progressive hepatic disease and renal disease; congestive heart failure; Body Mass Index (BMI) ≥35 kg/m2 where BMI reflects obesity and not high muscle mass;
•History of progressive or severe neurologic disorders, of any neurological symptoms or signs, or anaphylactic shock following administration of any study vaccine;
•Bleeding diathesis;

Outcomes

Primary Outcomes

Number of Subjects With at Least One Reactogenicity Sign After Two Doses of the Adjuvanted Pandemic Influenza Vaccine.

Time Frame: Up to 6 days after each vaccination.

To assess the safety and tolerability profile of two doses of the MF59-adjuvanted A/Vietnam/1194/2004 pandemic influenza vaccine (aH5N1), each containing 7.5 μg of H5N1 antigen in terms of the number of participants who reported local and systemic reactions up to 6 days after each vaccination per vaccination group.

Number of Subjects Exposed to Adjuvanted Pandemic Influenza Vaccine.

Time Frame: Upto Day 224 post vaccination

To report safety data from a large enough number of subjects exposed to adjuvanted pandemic influenza vaccine aH5N1 capable of detecting rare adverse events (AEs), i.e. events occurring at a frequency of \<=0.1%, \& uncommon AEs in elderly, i.e. occurring at a frequency of \<=1% of subjects.

Secondary Outcomes

Geometric Mean Ratios (GMRs) After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.(Day 43/Day 22, Day 64/Day 22)
The Number of Subjects With at Least One Reactogenicity Sign After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine as Compared With the Adjuvanted Seasonal Trivalent Influenza Vaccine aTIV.(Up to 6 days after each vaccination.)
GMTs After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.(Day 22, Day 43 and Day 64)
Percentages of Subjects Achieving Seroconversion or Significant Increase in Antibody Titers, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.(Day 43/Day 22 and Day 64/Day 22))
Percentages of Subjects Achieving at Least a Four-fold Rise in MN Antibody Titer on Day 43 and Day 64, Compared to Day 22 Against Homologous Strains.(Day 43/Day 22 and Day 64/Day 22)
Geometric Mean Titers (GMTs) After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.(Day 22, Day 43, Day 64)
Percentages of Subjects With HI Titers ≥ 40 and GMAs ≥ 25mm^2, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.(Day 22, Day 43 and Day 64)
Percentages of Subjects With MN Titers ≥20, ≥40, ≥80, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.(Day 22, Day 43 and Day 64)
GMRs After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.(Day 43/Day 22 and Day 64/Day 22)
Percentages of Subjects With MN Titers ≥20, ≥40, ≥80, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.(Day 22, Day 43 and Day 64)
Percentages of Subjects Achieving at Least a Four-fold Rise in MN Antibody Titer on Day 43 and Day 64, Compared to Day 22 Against Heterologous Strains.(Day 43/Day 22 and Day 64/Day 22)
Geometric Mean Areas (GMAs) After Two Doses of the Adjuvanted Pandemic Vaccine (aH5N1).(Day 22, Day 43, Day 64)
Percentages of Subjects Achieving Seroconversion or Significant Increase in Antibody Titer After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.(Day 43/Day 22 and Day 64/Day 22)
GMAs After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.(Day 22, Day 43 and Day 64)
Percentages of Subjects With HI ≥ 40 and GMAs ≥ 25mm^2, After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.(Day 22, Day 43 and Day 64)
Number of Subjects Reporting Unsolicited AEs After Vaccination.(Day 1 through Day 224 post vaccination)