Comparison of Safety, Tolerability and Immunogenicity of Influenza Vaccines in Adults and Elderly

A Phase III, Observer-Blind, Randomized, Multi-Center Study to Evaluate Safety, Tolerability and Immunogenicity (in a Subset) Following a Single Intramuscular Dose of a Trivalent Subunit Influenza Vaccine Produced Either in Mammalian Cell Culture or in Embryonated Hen Eggs, in Healthy Adult and Elderly Subjects Who Received Either One or the Other Vaccine One Year Before in the V58P4 Study.

The purpose of the study is to evaluate safety, tolerability and immunogenicity (in a subset) following a dose of a trivalent subunit influenza vaccine produced either in mammalian cells or in embryonated hen eggs, in healthy adult and elderly subjects who received either vaccine one year before (2004) in the study V58P4.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Cell culture derived influenza vaccine; Biological: egg-derived influenza subunit vaccine

• Study Type: Interventional
• Enrollment (Actual): 2235
• Phase: Phase 3

Contacts and Locations

Study Locations

• Poland
  • Kielce
    • Ul. Langiewicza 2, Kielce, Poland, 25-381
      • Wojewódzki Szpital Dzieci_cy
  • Krakow
    • Ul. Ujastek 3, Krakow, Poland, 30-969
      • Centrum Bada_ Farmakologii Klinicznej
  • Kraków
    • Centrum Medyczne Sp. Z O.o., O_. Jagiello_skie 1, Kraków, Poland, 31-832
      • NZOZ Jagiello_skie
    • Pl. Sikorskiego 6a, Kraków, Poland, 31-115
      • NZOZ Praktyka Grupowa Lekarzy Rodzinnych, "Familia" Sp. z o.o.
    • Ul. Pr_dnicka 80, Kraków, Poland, 31-202
      • Szpital Jana Pawła II, Oddz. Neuroinfekcji

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 to < 61 years of age (first age group) OR 61 years of age and older (second age group) at enrolment in V58P4
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. Available for all the visits scheduled in the study

5. in good health as determined by:

   1. Medical history related to the previous six months,
   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. Currently experiencing an acute infectious disease

3. Any serious disease such as, for example:

   1. Cancer (except for benign or localized skin cancer and non metastatic prostate cancer not currently treated with chemotherapy)
   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
4. Surgery planned during the study period
5. Bleeding diathesis
6. History of hypersensitivity to any component of the study medication or chemically related substances, such as allergy to eggs or egg products

7. Known or suspected impairment/alteration of immune function resulting from:

   1. Receipt of immunosuppressive therapy (any cortical steroid or cancer chemotherapy)
   2. Receipt of immunostimulants
   3. Receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within the past 3 months and for the full length of the study
   4. High risk for developing an immunocompromising disease
8. History of drug or alcohol abuse
9. Laboratory confirmed influenza disease in the past 6 months
10. Received influenza vaccine within the past 6 months
11. Received another vaccine or any investigational agent within the past 60 days, or expect to receive another vaccine within 3 weeks following the study vaccination
12. Participation in another clinical trial within 90 days prior to enrollment and throughout the full length of the study
13. Any acute respiratory disease or infections requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis is acceptable) or experienced fever _ 38°C within the past 5 days
14. Pregnant/ breast feeding women or women who refuse to use a reliable contraceptive method during the first three weeks after vaccination
15. Any condition which, 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: Single Group Assignment
• Masking: Single

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: cTIV\cTIV (adults); Subjects (18-60 years of age) previously vaccinated with cell-derived influenza vaccine (cTIV), received one dose of cell-derived trivalent influenza vaccine (cTIV) one year later, in this study.	Biological: Cell culture derived influenza vaccine; as a single IM injection of 0.5 ml in the deltoid muscle, preferably of the non-dominant arm
Active Comparator: cTIV\TIV (adults); Subjects (18-60 years of age) previously vaccinated with cell-derived influenza vaccine (cTIV), received one dose of an egg-derived trivalent influenza vaccine (TIV) one year later, in this study.	Biological: egg-derived influenza subunit vaccine; as a single IM injection of 0.5 ml in the deltoid muscle, preferably of the non-dominant arm
Active Comparator: cTIV\cTIV (elderly); Subjects (≥61 years of age) previously vaccinated with cell-derived influenza vaccine (cTIV), received one dose of cell-derived trivalent influenza vaccine (cTIV) one year later, in this study.	Biological: Cell culture derived influenza vaccine; as a single IM injection of 0.5 ml in the deltoid muscle, preferably of the non-dominant arm
Active Comparator: cTIV\TIV (elderly); Subjects (≥61years of age) previously vaccinated with cell-derived influenza vaccine (cTIV), received one dose of an egg-derived trivalent influenza vaccine (TIV) one year later, in this study.	Biological: egg-derived influenza subunit vaccine; as a single IM injection of 0.5 ml in the deltoid muscle, preferably of the non-dominant arm
Active Comparator: TIV\TIV (adults); Subjects (18-60 years of age) previously vaccinated with egg-derived influenza vaccine (TIV), received one dose of egg-derived trivalent influenza vaccine (TIV) one year later, in this study.	Biological: egg-derived influenza subunit vaccine; as a single IM injection of 0.5 ml in the deltoid muscle, preferably of the non-dominant arm
Active Comparator: TIV\cTIV (adults); Subjects (18-60 years of age) previously vaccinated with egg-derived influenza vaccine (TIV), received one dose of cell-derived trivalent influenza (cTIV) one year later, in this study.	Biological: Cell culture derived influenza vaccine; as a single IM injection of 0.5 ml in the deltoid muscle, preferably of the non-dominant arm
Active Comparator: TIV\TIV (elderly); Subjects (≥61 years of age) previously vaccinated with egg-derived influenza vaccine (TIV), received one dose of egg-derived trivalent influenza vaccine (TIV) one year later, in this study.	Biological: egg-derived influenza subunit vaccine; as a single IM injection of 0.5 ml in the deltoid muscle, preferably of the non-dominant arm
Active Comparator: TIV\cTIV (elderly); Subjects (≥61 years of age) previously vaccinated with egg-derived influenza vaccine (TIV), received one dose of cell-derived trivalent influenza (cTIV) one year later, in this study.	Biological: Cell culture derived influenza vaccine; as a single IM injection of 0.5 ml in the deltoid muscle, preferably of the non-dominant arm

What is the study measuring?

Primary 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 adult and elderly subjects reporting solicited adverse events following one dose of the cTIV or the TIV vaccine .	Day 1 to Day 7 postvaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Six-months Safety Data of Subjects After One Dose of Cell Culture Derived or Egg-derived Influenza Vaccine	To collect additional safety data for 6 months after vaccination with one dose of cell culture derived or egg-derived influenza vaccine 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.	Up to 6 months postvaccination
Geometric Mean Titers (GMTs) After One Dose of Cell Culture-derived or the Egg-derived Influenza Vaccine in Adult and Elderly Subjects	The haemagglutinin inhibition (HI) antibody titer response following one 0.5 mL dose of either cell derived (cTIV) or egg-derived vaccine (TIV) in adult and elderly subjects is reported as GMTs. The HI GMTs were evaluated using egg-derived antigen assay.	Day 22 postvaccination
Geometric Mean Ratios (GMRs), After One Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in Adult and Elderly Subjects	Immunogenicity was assessed in terms of GMR in adult and elderly subjects following one 0.5ml dose of either the cTIV vaccine or the TIV vaccine, according to the CHMP criteria. The European licensure (CHMP) criteria was met if the mean geometric increase (GMR, day 22/day 1) in HI antibody titer is >2.5 for adults and >2.0 for elderly subjects.	Day 22 postvaccination
Percentages of Adult and Elderly Subjects Achieving HI Titers ≥ 40 After One Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine.	Immunogenicity was assessed in terms of percentages of adult and elderly subjects achieving HI titers≥40,after one dose of either the cTIV vaccine or the TIV vaccine. European (CHMP) criteria is met if the percentage of subjects achieving HI titers ≥ 40 is > 70% for adults and >60% for elderly.	Day 22 postvaccination
Percentages of Adult and Elderly Subjects With Seroconversion or Significant Increase in HI Antibody Titers After One Dose of Cell Culture-derived or the Egg-derived Influenza Vaccine.	Immunogenicity was assessed in terms of percentages of adult and elderly subjects showing seroconversion or significant increase in HI antibody titers after one dose of cell culture-derived or the egg-derived influenza vaccine. Seroconversion or significant increase as per European Licensure (CHMP) criteria is defined as percentage of subjects with a prevaccination HI titer <10 to a postvaccination titer ≥ 40 for adults and ≥ 30 for elderly. Significant increase is defined as percentage of subjects with a prevaccination HI titer ≥ 10 and a ≥ 4-fold increase in postvaccination HI antibody titer.	Day 22 postvaccination

Collaborators and Investigators

• Sponsor: Novartis Vaccines
• Collaborators: Novartis Vaccines and Diagnostics S.r.l.

Publications and helpful links

General Publications

• Szymczakiewicz-Multanowska A, Lattanzi M, Izu A, Casula D, Sparacio M, Kovacs C, Groth N. Safety assessment and immunogenicity of a cell-culture-derived influenza vaccine in adults and elderly subjects over three successive influenza seasons. Hum Vaccin Immunother. 2012 May;8(5):645-52. doi: 10.4161/hv.19493. Epub 2012 May 1.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: March 22, 2006
• First Submitted That Met QC Criteria: March 22, 2006
• First Posted (Estimate): March 24, 2006

Study Record Updates

• Last Update Posted (Actual): August 14, 2019
• Last Update Submitted That Met QC Criteria: August 2, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: vaccine; Influenza; adult/elderly; flu cell culture
• 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: V58P4E1; EUDRACT: 2005-001902-26