Safety of a Influenza Vaccine Produced Either in Mammalian Cell Culture or in Embryonated Hen Eggs in Adults and Elderly With and Without Underlying Medical Conditions, and Immunogenicity in a Subset of Subjects With Underlying Medical Conditions

Phase 4

Completed

• Conditions: Seasonal Influenza; Vaccine
• Interventions: Biological: Cell-derived influenza vaccine; Biological: Egg-derived influenza vaccine

• Registration Number: NCT00560066
• Lead Sponsor: Novartis Vaccines

Brief Summary

Evaluation of the safety of Trivalent Subunit Influenza Vaccine Produced either in Mammalian Cell Culture or in embryonated Hen Eggs in subjects 18 years of age and above with and without underlying medical conditions and evaluation of the immunogenicity in a subset of subjects with underlying medical conditions, compared to an egg-based vaccine in a post marketing setting.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-11
• Study First Submitted: 2007-11-16
• Study First Submitted QC: 2007-11-16
• Study First Posted: 2007-11-19
• Primary Completion: 2008-07
• Study Completion: 2008-07
• Disposition First Submitted: 2011-12-13
• Disposition First Submitted QC: 2011-12-13
• Disposition First Posted: 2011-12-22
• Results First Submitted: 2012-11-21
• Results First Submitted QC: 2013-04-17
• Results First Posted: 2013-04-18
• Status Verified: 2016-01
• Last Update Submitted: 2016-01-19
• Last Update Posted: 2016-02-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1398

Inclusion Criteria

1. Subjects 18 years of age and above, mentally competent, willing and able to give informed consent prior to study entry;
2. Able to comply with all study procedures and requirements.

Exclusion Criteria

1. History of any anaphylaxis, serious vaccine reactions, or hypersensitivity to any vaccine component;
2. Fatal prognosis of an underlying medical condition (<12 months life expectancy);
3. History of Guillain-Barre syndrome;
4. Bleeding diathesis or receiving anticoagulants of the coumarin type;
5. Hospitalization or residence in a nursing care facility;
6. Planned to receive seasonal influenza vaccine outside of this study;
7. Receipt of another vaccine within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study;
8. Fever (defined as axillary temperature ≥38.0°C) or any acute illness within 3 days prior to study vaccination;
9. Receipt of another investigational agent within 30 days prior to enrollment in the study or before completion of the safety follow-up period in another study, whichever is longer, and unwilling to refuse participation in another clinical study through the end safety follow up period of the study;
10. Any condition, which, in the opinion of the investigator, might prevent the subject from participation or interfere with the evaluation of the study objectives;
11. Females who were pregnant or nursing (breastfeeding) mothers, or females of childbearing potential who were sexually active and had not used or did not plan to use acceptable birth control measures during the first 3 weeks after vaccination. Oral, injected or implanted hormonal contraceptive, diaphragm or condom with spermicidal agent or intrauterine device were considered acceptable forms of birth control.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
cTIV	Cell-derived influenza vaccine	Subjects received one vaccination of cell culture-derived influenza vaccine
TIV	Egg-derived influenza vaccine	Subjects received one vaccination of egg-derived influenza vaccine

Primary Outcome Measures

Name	Time	Method
Number of Subjects Who Reported At Least One Reactogenicity Sign After One Vaccination of TIV or cTIV	From Day 1 up to and including Day 7 post-vaccination	Safety was assessed as the number of all subjects who reported at least one sign of reactogenicity after one vaccination of egg-derived (TIV) or cell culture-derived (cTIV) influenza virus vaccine from Day 1 through Day 7 post-vaccination.

Secondary Outcome Measures

Name	Time	Method
Number of Healthy Adults and Elderly Who Reported Solicited Local and Systemic Adverse Events (AEs) After One Vaccination of TIV or cTIV	From Day 1 through Day 7 post-vaccination	Analysis was performed on a subset of safety population which included the healthy adults (≥18 to ≤60 years) and elderly (≥61 years).
Number of Adults and Elderly With Underlying Medical Conditions Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV or cTIV	From Day 1 through Day 7 post-vaccination	Analysis was performed on a subset of safety population which included the adults (≥18 to ≤60 years) and elderly (≥61 years) with underlying medical conditions.
Percentages Of Subjects With Underlying Medical Conditions Who Achieved Hemagglutination Inhibition (HI) Titer ≥40 After One Vaccination of TIV or cTIV	Before vaccination (Day 1) and three weeks after vaccination (Day 22)	Immunogenicity was measured as the percentage of adults (≥18 to ≤60 years) and elderly (≥61 years) achieving HI titers ≥40 at baseline (Day 1) and three weeks (Day 22) after one vaccination of TIV or cTIV for each of three vaccine strains, evaluated using hemagglutination inhibition (HI) egg-derived antigen assay. This criterion is met according to European (CHMP) guideline if the percentage of subjects achieving HI titers ≥40 is \>70% (≥18 to ≤60 years), or \>60% (≥61 years).
Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titers After One Vaccination of TIV or cTIV	Three weeks post-vaccination (Day 22)	Seroconversion or significant increase in HI titer as per CHMP criteria for each of the three strains is defined as the percentage of subjects with a prevaccination HI titer \<10 to a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, a ≥4-fold increase in postvaccination HI antibody titer. According to the CHMP criteria, the percentage of subjects achieving seroconversion/significant increase should be \>40% (≥18 to ≤60 years) or \>30% (≥61 years).
Geometric Mean Titers of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV	Before vaccination (Day 1) and three weeks after vaccination (Day 22)	Immunogenicity was measured as HI geometric mean titers (GMTs) of subjects with underlying conditions, directed against each of three vaccine strains at baseline (Day 1) and three weeks after vaccination (Day 22) in adults (≥18 to ≤60 years) and elderly (≥61 years).
Geometric Mean Ratio of Subjects With Underlying Medical Conditions After One Vaccination of TIV or cTIV	Three weeks post-vaccination (Day 22)	Immunogenicity was measured as the geometric mean ratio (GMR), calculated as the ratio of postvaccination to prevaccination HI GMTs for each of the three strains, three weeks after one vaccination (Day 22) of TIV or cTIV. CHMP criteria is considered fulfilled for each of the three strains if the geometric mean increase GMR (Day 22/Day 1) in HI antibody titer is \>2.5 (≥18 to ≤60 years) or \>2.0 (≥61 Years).