Clinical trial NCT00264576: Study of the Safety and Immunogenicity of an Influenza Vaccine Administered to Healthy Adults
Official title: A Phase 2, Observer-Blinded, Randomized, Multicenter Study in Healthy Adults to Evaluate Safety and Tolerability and to Compare Immunogenicity of a Single Dose of Either an Investigational Trivalent Inactivated Influenza Vaccine Produced in Mammalian Cell Culture or a US-licensed Trivalent Inactivated Influenza Vaccine (Fluvirin®) Produced in Embryonated Hen Eggs
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza Disease; Flu
Keywords: influenza
flu
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Novartis Vaccines and Diagnostics (formerly Chiron Vaccines)
First posted: 2005-12-13
Enrollment: 613
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Geometric Mean Titers (GMT) After 1 Dose of Cell-culture-derived Vaccine (cTIV) or Egg-derived Vaccine (eTIV_f), Using the ANOVA Method.
timeFrame: 3 weeks postvaccination (Day 22)
measure: Geometric Mean Titers (GMT) After 1 Dose of Cell-culture-derived Vaccine (cTIV) or Egg-derived Vaccine (eTIV_f), Using the ANCOVA Method.
timeFrame: 3 weeks postvaccination (Day 22)
Secondary outcomes:
measure: Geometric Mean Ratio After 1 Dose of Cell-culture-derived Vaccine (cTIV) or Egg-derived Vaccine (eTIV_f), Using the ANOVA Method.
timeFrame: 3 weeks postvaccination (Day 22)
measure: Geometric Mean Ratio After 1 Dose of Cell-culture-derived Vaccine (cTIV) or Egg-derived Vaccine (eTIV_f), Using the ANCOVA Method.
timeFrame: 3 weeks postvaccination (Day 22)
measure: 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
timeFrame: 3 weeks postvaccination (Day 22)
measure: Percentages of Subjects With Haemagglutination Inhibition (HI) Antibody Titer ≥ 40.
timeFrame: 3 weeks postvaccination (Day 22)
measure: Percentages of Subjects With Seroconversion.
timeFrame: 3 weeks postvaccination (Day 22)
measure: Number of Subjects Reporting Local and Systemic Reactions
timeFrame: 7 days postvaccination
Other outcomes:
Locations:
city: Bardstown
country: United States
state: Kentucky
city: Pittsburgh
country: United States
state: Pennsylvania
city: Salt Lake City
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
Study officials:
affiliation: Novartis Vaccines
name: Novartis Vaccines
role: STUDY_CHAIR
References:
citation: Reisinger KS, Block SL, Izu A, Groth N, Holmes SJ. Subunit influenza vaccines produced from cell culture or in embryonated chicken eggs: comparison of safety, reactogenicity, and immunogenicity. J Infect Dis. 2009 Sep 15;200(6):849-57. doi: 10.1086/605506.