Clinical trial NCT00841763: Safety, Tolerability and Immunogenicity of Two Doses of Adjuvanted Monovalent Influenza Vaccine Administered to Healthy Adult and Elderly Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pandemic Influenza Disease
Keywords: virus
pandemic influenza
vaccine
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Novartis Vaccines
First posted: 2009-02-11
Enrollment: 3647
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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:

  1. medical history,
  2. physical examination,
  3. 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;
* Surgery planned during the study period;
* Hypersensitivity to eggs, chicken protein, chicken feathers, influenza viral protein, neomycin or polymyxin or any other component of the study vaccines;
* Known or suspected impairment/alteration of immune function, for example, resulting from:

  1. receipt of immunosuppressive therapy (any corticosteroid therapy or cancer chemotherapy) or other immunosuppressive agents within the past 60 days and for the full length of the study;
  2. receipt of immunostimulants;
  3. receipt of parenteral immunoglobulin preparation, blood products and/or plasma derivates within the past 3 months and for the full length of the study;
  4. suspected or known HIV infection or HIV-related disease;
* Receipt of non study vaccines (with the exception of post-exposure vaccination in a medical emergency, e.g. hepatitis, rabies, tetanus) within 3 weeks prior to Visit 1 or planned vaccination within 3 weeks following the last study vaccination;
* History of (or current) drug or alcohol abuse that in the investigator's opinion would interfere with safety of the subject or the evaluation of study objectives;
* Members of research staff and their relatives;
* Any condition, which, in the opinion of the Investigator, might interfere with the evaluation of the study objectives.

Primary outcomes:
measure: Number of Subjects With at Least One Reactogenicity Sign After Two Doses of the Adjuvanted Pandemic Influenza Vaccine.
timeFrame: Up to 6 days after each vaccination.
measure: Number of Subjects Exposed to Adjuvanted Pandemic Influenza Vaccine.
timeFrame: Upto Day 224 post vaccination
Secondary outcomes:
measure: 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.
timeFrame: Up to 6 days after each vaccination.
measure: Geometric Mean Titers (GMTs) After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.
timeFrame: Day 22, Day 43, Day 64
measure: Geometric Mean Areas (GMAs) After Two Doses of the Adjuvanted Pandemic Vaccine (aH5N1).
timeFrame: Day 22, Day 43, Day 64
measure: Geometric Mean Ratios (GMRs) After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Homologous A/Vietnam/1194/2004 Strain.
timeFrame: Day 43/Day 22, Day 64/Day 22
measure: 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.
timeFrame: Day 22, Day 43 and Day 64
measure: 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.
timeFrame: Day 43/Day 22 and Day 64/Day 22
measure: GMTs After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.
timeFrame: Day 22, Day 43 and Day 64
measure: GMAs After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.
timeFrame: Day 22, Day 43 and Day 64
measure: GMRs After Two Doses of the Adjuvanted Pandemic aH5N1 Vaccine Against the Heterologous A/Turkey/Turkey/1/2005 Strain.
timeFrame: Day 43/Day 22 and Day 64/Day 22
measure: 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.
timeFrame: Day 22, Day 43 and Day 64
measure: 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.
timeFrame: Day 43/Day 22 and Day 64/Day 22)
measure: 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.
timeFrame: Day 22, Day 43 and Day 64
measure: 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.
timeFrame: Day 22, Day 43 and Day 64
measure: 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.
timeFrame: Day 43/Day 22 and Day 64/Day 22
measure: 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.
timeFrame: Day 43/Day 22 and Day 64/Day 22
measure: Number of Subjects Reporting Unsolicited AEs After Vaccination.
timeFrame: Day 1 through Day 224 post vaccination
Other outcomes:
Locations:
city: Tampere
country: Finland
facility: Tampere Vaccine Research Clinic (15 sites)
city: München
country: Germany
facility: 12 Sites
Study officials:
affiliation: Novartis Vaccines
name: Novartis Vaccines
role: STUDY_DIRECTOR
References:
citation: Vesikari T, Forsten A, Herbinger KH, Cioppa GD, Beygo J, Borkowski A, Groth N, Bennati M, von Sonnenburg F. Safety and immunogenicity of an MF59((R))-adjuvanted A/H5N1 pre-pandemic influenza vaccine in adults and the elderly. Vaccine. 2012 Feb 8;30(7):1388-96. doi: 10.1016/j.vaccine.2011.12.009. Epub 2011 Dec 20.