Study of the Safety and Immunogenicity of an Influenza Vaccine Administered to Healthy Adults

Phase 2

Completed

• Conditions: Influenza Disease; Flu
• Interventions: Biological: Influenza Virus Vaccine

• Registration Number: NCT00264576
• Lead Sponsor: Novartis Vaccines

Brief Summary

The purpose of this study is to evaluate the safety and immunogenicity of cell culture-derived, inactivated, subunit influenza vaccine in comparison to licensed Fluvirin vaccine administered to healthy adults ages 18 \< 50 years.

Detailed Description

Not available

Study Timeline

• Study Start: 2005-10
• Primary Completion: 2005-12
• Study First Submitted: 2005-12-09
• Study First Submitted QC: 2005-12-09
• Study First Posted: 2005-12-13
• Study Completion: 2006-05
• Status Verified: 2012-12
• Results First Submitted: 2012-12-20
• Results First Submitted QC: 2012-12-20
• Results First Posted: 2013-01-28
• Last Update Submitted: 2017-02-21
• Last Update Posted: 2017-03-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 613

Inclusion Criteria

18 to <50 years of age;

1. able to comprehend and follow all required study procedures;

2. able and willing to provide written informed consent prior to study entry;

3. available for all the visits scheduled in the study;

4. in general good health as determined by:

   1. subject-reported medical history,
   2. physical examination by a qualified study nurse, a physician's assistant, or a physician,
   3. clinical judgment of the investigator; among all female volunteers, evidence of a negative pregnancy test conducted on the same day as and prior to study vaccination, and agreement to practice adequate contraception for at least 6 weeks after vaccination as further described in the protocol.

Exclusion Criteria

1. received influenza vaccine within the past 6 months;

2. laboratory-confirmed influenza disease in the past 6 months;

3. any acute respiratory disease or infection requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis was acceptable) or fever ≥38°C (100.4°F) within the past 3 days;

4. receipt of another investigational agent within 90 days or before completion of the safety follow-up period in another study, whichever was longer, prior to enrollment, and unwilling to refuse participation in another investigational study through the end of the study;

5. any history of or current serious disease, such as: d) cancer (except for benign or localized skin cancer), e) autoimmune disease (including rheumatoid arthritis), f) advanced arteriosclerotic disease or diabetes mellitus, g) chronic obstructive pulmonary disease (COPD), h) acute, chronic, or progressive hepatic disease, i) acute, chronic, or progressive renal disease, j) congestive heart failure, k) bleeding diathesis, l) an inherited genetic anomaly (known cytogenic disorders, e.g., Down's Syndrome), m) any other serious, acute, or chronic disease including progressive neurological disease or seizure disorder unrelated to fever;

6. surgery or hospitalization planned during the study period;

7. history of any anaphylaxis, serious vaccine reactions, vaccine-associated oculorespiratory syndrome, or allergy to eggs, egg products, mercury-containing compounds (such as sodium-ethyl-mercuro-thio-salicylate), or any other vaccine component or component of the potential packaging materials (latex);

8. known or suspected disease of the immune system, or receiving immunosuppressive therapy, including use of: n) systemic corticosteroids, known to be associated with suppression of the hypothalamic-pituitary-adrenal (HPA) axis (i.e., systemic corticosteroids [15 mg/day of prednisone or its equivalent] or chronic use of inhaled high potency corticosteroids [budesonide 800 μg/day or fluticasone 750 μg/day]), both within the previous 60 days, o) receipt of immunostimulants within 60 days, p) receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within the 3 months prior to study entry or anticipated during the full length of the study;

9. at high risk for developing an immunocompromising disease;

10. 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;

11. pregnant or breastfeeding;

12. if female of childbearing potential, refusal to use a reliable contraceptive method, as described further in the protocol, during the first 6 weeks after vaccination;

13. if female of childbearing potential and sexually active, has not used any of the following birth control methods for the specified time period prior to study entry:

    1. hormonal (e.g., oral, injection, transdermal patch, implant, cervical ring), barrier (e.g., condom with spermicide or diaphragm with spermicide), or intrauterine device (e.g., IUD) for 2 months or more prior to study entry,
    2. monogamous relationship with vasectomized partner: partner has been vasectomized for 6 months or more prior to the subject's study entry;

14. obese (e.g., with a body mass index [BMI] ≥35, where BMI reflects obesity and not high muscle mass);

15. any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives or might interfere with the safety of the study subject.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
cTIV	Influenza Virus Vaccine	Received one dose of cell-culture derived trivalent influenza vaccine (cTIV).
TIV	Influenza Virus Vaccine	Received one dose of egg-derived trivalent vaccine (TIV).

Primary Outcome Measures

Name	Time	Method
Geometric Mean Titers (GMT) After 1 Dose of Cell-culture-derived Vaccine (cTIV) or Egg-derived Vaccine (eTIV_f), Using the ANOVA Method.	3 weeks postvaccination (Day 22)	Non-inferiority was measured by the ratio of postvaccination geometric mean titers (cTIV vs. eTIV_f) against all three vaccine strains as assessed by egg-derived antigen and cell-derived antigen haemagglutination inhibition (HI) assay.
Geometric Mean Titers (GMT) After 1 Dose of Cell-culture-derived Vaccine (cTIV) or Egg-derived Vaccine (eTIV_f), Using the ANCOVA Method.	3 weeks postvaccination (Day 22)	Non-inferiority was measured by the ratio of postvaccination geometric mean titers (cTIV vs. eTIV_f) against all three vaccine strains as assessed by egg-derived antigen and cell-derived antigen haemagglutination inhibition (HI) assay.

Secondary Outcome Measures

Name	Time	Method
Geometric Mean Ratio After 1 Dose of Cell-culture-derived Vaccine (cTIV) or Egg-derived Vaccine (eTIV_f), Using the ANOVA Method.	3 weeks postvaccination (Day 22)	Geometric mean ratio (GMR) of Day 22 / Day 1 geometric mean antibody titers was assessed by egg-derived antigen and cell-derived antigen haemagglutination inhibition (HI) assay.; The criterion is met according to European (CHMP) guideline if the mean geometric increase GMR (Day22/Day1) in HI antibody titer is \> 2.5.
Geometric Mean Ratio After 1 Dose of Cell-culture-derived Vaccine (cTIV) or Egg-derived Vaccine (eTIV_f), Using the ANCOVA Method.	3 weeks postvaccination (Day 22)	Geometric mean ratio (GMR) of Day 22 / Day 1 geometric mean antibody titers was assessed by egg-derived antigen and cell-derived antigen haemagglutination inhibition (HI) assay.; The criterion is met according to European (CHMP) guideline if the mean geometric increase GMR (Day22/Day1) in HI antibody titer is \> 2.5.
Geometric Mean Titers (GMT) Before and After 1 Dose of Cell-culture-derived Vaccine (cTIV) or Egg-derived Vaccine (eTIV_f), Using the ANOVA Method	3 weeks postvaccination (Day 22)	Antibody titers as assessed by egg-derived antigen and cell-derived antigen haemagglutination inhibition (HI) assay.
Percentages of Subjects With Haemagglutination Inhibition (HI) Antibody Titer ≥ 40.	3 weeks postvaccination (Day 22)	Antibody titers as assessed by egg-derived antigen and cell-derived antigen HI assay.; This criterion is met according to European (CHMP) guideline if the percentages of subjects achieving HI titers ≥40 is \>70%. According to the US Center for Biologics Evaluation and Research (CBER) guideline, the criterion is also met if the lower limit of the 95% CI for percentages of subjects achieving seroprotection (HI antibody titer ≥1:40) is ≥70%.
Percentages of Subjects With Seroconversion.	3 weeks postvaccination (Day 22)	As the definition for seroconversion/significant increase from CHMP guideline CPMP/BWP/214/96 corresponds to that of seroconversion from the May 2007 CBER guidance, the analysis of this immunogenicity endpoint is presented as seroconversion. Seroconversion is defined as prevaccination HI titer \<10 and postvaccination HI titer ≥40, or prevaccination HI titer ≥10 and a ≥4-fold increase in postvaccination HI antibody titer, on day 22. CBER criterion is met if the lower limit of the 95% CI for percentages of subjects achieving seroconversion for HI antibody (at least a 4-fold rise in HI antibody titer) postvaccination is ≥40%. CHMP criterion is also met if the percentages of subjects achieving seroconversion is \>40%.
Number of Subjects Reporting Local and Systemic Reactions	7 days postvaccination	Safety and tolerability of cTIV and eTIV_f postvaccination.; Difference between demography and safety numbers was due to one misrandomization.