Safety and Immunogenicity of 3 Lots of Cell-derived Subunit Influenza Vaccine as Compared to 1 Lot to Egg-derived Subunit Influenza Vaccine in Healthy Adults (>=18 to <=60)

A Phase III, Randomized, Controlled, Observer-Blind, Multi-Center Study to Evaluate Safety, Tolerability and Immunogenicity of a Single Intramuscular Dose of Three Lots of a Trivalent Subunit Influenza Vaccine Produced in Mammalian Cell Culture Or of a Trivalent Subunit Influenza Vaccine Produced in Embryonated Hen Eggs, in Healthy Adult Subjects Aged >=18 to <=60

The present study aims to evaluate safety, tolerability and immunogenicity of three lots of Chiron's cell-derived subunit influenza vaccine in healthy adult subjects as compared to a conventional egg-derived control vaccine licensed in Europe.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Cell-Derived Trivalent Subunit Influenza Vaccine Lot 1 (cTIV); Biological: Cell-Derived Trivalent Subunit Influenza Vaccine Lot 2 (cTIV); Biological: Cell-Derived Trivalent Subunit Influenza Vaccine Lot 3 (cTIV); Biological: Egg-Derived Trivalent Subunit Influenza Vaccine (TIV)

• Study Type: Interventional
• Enrollment (Actual): 1200
• Phase: Phase 3

Contacts and Locations

Study Locations

• Lithuania
  • Panevezys, Lithuania
    • 2nd Department of Internal Diseases, Panevezys Hospital,
  • Vilnius, Lithuania
    • Dept. Infectious Diseases and Microbiology of Vilnius University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 to <61 years of age
2. mentally competent to understand the nature, the scope and the consequences of the study
3. able and willing to give written informed consent prior to study entry

4. in good health as determined by:

   1. medical history,
   2. physical examination,
   3. clinical judgment of the Investigator.

Exclusion Criteria:

1. unwilling or unable to give written informed consent to participate in the study
2. participation in another clinical trial of an investigational agent within 90 days prior to Visit 1 and throughout the entire study
3. currently experiencing an acute infectious disease

4. any serious disease, such as, for example:

   1. cancer,
   2. autoimmune disease (including rheumatoid arthritis),
   3. advanced arteriosclerotic disease or complicated diabetes mellitus,
   4. chronic obstructive pulmonary disease (COPD) requiring oxygen therapy,
   5. acute or progressive hepatic disease,
   6. acute or progressive renal disease,
   7. congestive heart failure
5. surgery planned during the study period
6. bleeding diathesis
7. history of hypersensitivity to any component of the study medication or chemically related substances
8. history of any anaphylaxis, serious vaccine reactions, or allergy to any of the vaccine component

9. known or suspected impairment/alteration of immune function, for example resulting from:

   1. receipt of immunosuppressive therapy (any corticosteroid therapy or cancer chemotherapy),
   2. receipt of immunostimulants,
   3. receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivates within 3 months prior to Visit 1 or planned during the full length of the study,
   4. high risk for developing an immunocompromising disease
10. history of drug or alcohol abuse
11. laboratory-confirmed influenza disease within 6 months prior to Visit 1
12. receipt of influenza vaccine within 6 months prior to Visit 1
13. receipt of another vaccine within 60 days prior to Visit 1, or planned vaccination within 3 weeks following study vaccination
14. any acute respiratory disease or infections requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis is acceptable) or experienced fever (i.e., axillary temperature ≥ 38 degree C) within 5 days prior to Visit 1
15. if female, pregnant or breastfeeding
16. if female, refusal to use a reliable contraceptive method during the three weeks following vaccination
17. planned relocation abroad during the study period
18. any condition that, in the opinion of the Investigator, might interfere with the evaluation of the study objectives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cTIV_lot 1	Biological: Cell-Derived Trivalent Subunit Influenza Vaccine Lot 1 (cTIV); One single 0.5ml intramuscular injection of Cell Derived Trivalent Subunit Influenza Vaccine (cTIV) from Lot 1
Experimental: cTIV_lot 2	Biological: Cell-Derived Trivalent Subunit Influenza Vaccine Lot 2 (cTIV); One single 0.5ml intramuscular injection of Cell Derived Trivalent Subunit Influenza Vaccine (cTIV) from Lot 2
Experimental: cTIV_lot 3	Biological: Cell-Derived Trivalent Subunit Influenza Vaccine Lot 3 (cTIV); One single 0.5ml intramuscular injection of Cell Derived Trivalent Subunit Influenza Vaccine (cTIV) from Lot 3
Active Comparator: TIV group	Biological: Egg-Derived Trivalent Subunit Influenza Vaccine (TIV); One single 0.5ml intramuscular injection of Egg Derived Trivalent Subunit Influenza Vaccine (TIV).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers After One Dose of Cell Culture-derived or the Egg-derived Influenza Vaccine in Adult Subjects	The haemagglutinin Inhibition (HI) antibody titer response following; one dose of cTIV for each of the three lots separately and; one dose of cTIV (combined) compared to TIV is reported as Geometric mean titers (GMTs). The HI GMTs were evaluated using egg-derived antigen assay.	Day 22 postvaccination
Geometric Mean Ratios After One Dose of Cell Culture-derived or the Egg-derived Influenza Vaccine in Adult Subjects	Immunogenicity was assessed in terms of Geometric Mean Ratio (GMR) following; one dose of cTIV for each of the three vaccine lots separately and; for one dose of cTIV (combined) compared to TIV, according to the CHMP criterion. The European licensure (CHMP) criterion is met if the mean geometric increase (GMR, day 22/day 1) in HI antibody titer is >2.5.	Day 22 postvaccination
Percentage of Subjects With HI Titers ≥40	Immunogenicity was assessed in terms of percentage of adult subjects achieving HI titers ≥40, after; one dose of cTIV for each of the three vaccine lots separately and; for one dose of cTIV (combined) compared to TIV, according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving HI titers ≥40 is >70%.	Day 22 postvaccination
Percentage of Subjects With Seroconversion or Significant Increase in HI Antibody Titers After One Dose of Either Cell-derived or Egg-derived Subunit Trivalent Influenza Vaccine	Immunogenicity was assessed in terms of percentage of adult subjects showing seroconversion or significant increase in HI antibody titers after; one dose of cTIV for each of the three vaccine lots separately and; one dose of cTIV (combined) compared to TIV, according to the CHMP criterion. European Licensure (CHMP) criterion is met if the percentage of subjects achieving seroconversion or significant increase is >40%. As per European Licensure (CHMP) criterion seroconversion is defined as percentage of subjects with a prevaccination HI titer <10 to a postvaccination titer ≥40; whereas, significant increase is defined as HI titer ≥10 prevaccination and ≥4-fold Hi titer increase post-vaccination.	Day 22 postvaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Reporting Solicited Adverse Events After One Dose of Cell Culture-derived or the Egg-derived Influenza Vaccine.	To assess the safety and tolerability in terms of number of subjects reporting solicited adverse events following one injection of; one dose of cTIV for each of the three vaccine lots separately and; for one dose of cTIV (combined) compared to TIV.	Day 1 to Day 7 postvaccination
Safety Data of Subjects Upto Six Months After One Dose of Cell Culture Derived or Egg-derived Influenza Vaccine	Additional safety data from day 1 through day 181 after one dose of cTIV (combined) or TIV in terms of serious adverse events (SAEs), adverse events (AEs) necessitating a physician's visit and/or resulting in premature subject's withdrawal from study is reported.	Day 1 - Day 181 postvaccination

Collaborators and Investigators

• Sponsor: Novartis Vaccines
• Investigators: Study Chair: Novartis Vaccines, Novartis Vaccines & Diagnostics

Publications and helpful links

General Publications

• Ambrozaitis A, Groth N, Bugarini R, Sparacio V, Podda A, Lattanzi M. A novel mammalian cell-culture technique for consistent production of a well-tolerated and immunogenic trivalent subunit influenza vaccine. Vaccine. 2009 Oct 9;27(43):6022-9. doi: 10.1016/j.vaccine.2009.07.083. Epub 2009 Aug 8.

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): October 1, 2005
• Study Completion (Actual): April 1, 2006

Study Registration Dates

• First Submitted: April 3, 2006
• First Submitted That Met QC Criteria: April 3, 2006
• First Posted (Estimate): April 5, 2006

Study Record Updates

• Last Update Posted (Actual): August 15, 2019
• Last Update Submitted That Met QC Criteria: August 2, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Safety; Influenza; Immunogenicity; Vaccination; Flu; Healthy Adults; Cell-Derived; Egg-Derived
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: V58P9; EUDRACT: 2005-002257-47