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

Primary Purpose

Influenza

Status
Completed
Phase
Phase 3
Locations
Poland
Study Type
Interventional
Intervention
Cell culture derived influenza vaccine
egg-derived influenza subunit vaccine
Sponsored by
Novartis Vaccines
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Influenza focused on measuring Influenza, adult/elderly, flu cell culture, vaccine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: 18 to < 61 years of age (first age group) OR 61 years of age and older (second age group) at enrolment in V58P4 Mentally competent to understand the nature, the scope and the consequences of the study Able and willing to give written informed consent prior to study entry Available for all the visits scheduled in the study in good health as determined by: Medical history related to the previous six months, Physical examination, Clinical judgment of the investigator. Exclusion Criteria: Unwilling or unable to give written informed consent to participate in the study Currently experiencing an acute infectious disease Any serious disease such as, for example: Cancer (except for benign or localized skin cancer and non metastatic prostate cancer not currently treated with chemotherapy) Autoimmune disease (including rheumatoid arthritis) Advanced arteriosclerotic disease or complicated diabetes mellitus Chronic obstructive pulmonary disease (COPD) requiring oxygen therapy Acute or progressive hepatic disease Acute or progressive renal disease Congestive heart failure Surgery planned during the study period Bleeding diathesis History of hypersensitivity to any component of the study medication or chemically related substances, such as allergy to eggs or egg products Known or suspected impairment/alteration of immune function resulting from: Receipt of immunosuppressive therapy (any cortical steroid or cancer chemotherapy) Receipt of immunostimulants Receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within the past 3 months and for the full length of the study High risk for developing an immunocompromising disease History of drug or alcohol abuse Laboratory confirmed influenza disease in the past 6 months Received influenza vaccine within the past 6 months 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 Participation in another clinical trial within 90 days prior to enrollment and throughout the full length of the study 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 Pregnant/ breast feeding women or women who refuse to use a reliable contraceptive method during the first three weeks after vaccination Any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.

Sites / Locations

  • Wojewódzki Szpital Dzieci_cy
  • Centrum Bada_ Farmakologii Klinicznej
  • NZOZ Jagiello_skie
  • NZOZ Praktyka Grupowa Lekarzy Rodzinnych, "Familia" Sp. z o.o.
  • Szpital Jana Pawła II, Oddz. Neuroinfekcji

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

cTIV\cTIV (adults)

cTIV\TIV (adults)

cTIV\cTIV (elderly)

cTIV\TIV (elderly)

TIV\TIV (adults)

TIV\cTIV (adults)

TIV\TIV (elderly)

TIV\cTIV (elderly)

Arm Description

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.

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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 .

Secondary Outcome Measures

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.
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.
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.
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.
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.

Full Information

First Posted
March 22, 2006
Last Updated
August 2, 2019
Sponsor
Novartis Vaccines
Collaborators
Novartis Vaccines and Diagnostics S.r.l.
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1. Study Identification

Unique Protocol Identification Number
NCT00306527
Brief Title
Comparison of Safety, Tolerability and Immunogenicity of Influenza Vaccines in Adults and Elderly
Official Title
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.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
September 2005 (undefined)
Primary Completion Date
December 2005 (Actual)
Study Completion Date
April 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Vaccines
Collaborators
Novartis Vaccines and Diagnostics S.r.l.

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza
Keywords
Influenza, adult/elderly, flu cell culture, vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
Participant
Allocation
Randomized
Enrollment
2235 (Actual)

8. Arms, Groups, and Interventions

Arm Title
cTIV\cTIV (adults)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
cTIV\TIV (adults)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
cTIV\cTIV (elderly)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
cTIV\TIV (elderly)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
TIV\TIV (adults)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
TIV\cTIV (adults)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
TIV\TIV (elderly)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
TIV\cTIV (elderly)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Cell culture derived influenza vaccine
Intervention Description
as a single IM injection of 0.5 ml in the deltoid muscle, preferably of the non-dominant arm
Intervention Type
Biological
Intervention Name(s)
egg-derived influenza subunit vaccine
Intervention Description
as a single IM injection of 0.5 ml in the deltoid muscle, preferably of the non-dominant arm
Primary Outcome Measure Information:
Title
Number of Subjects Reporting Solicited Adverse Events After One Dose of Cell Culture-derived or the Egg-derived Influenza Vaccine
Description
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 .
Time Frame
Day 1 to Day 7 postvaccination
Secondary Outcome Measure Information:
Title
Six-months Safety Data of Subjects After One Dose of Cell Culture Derived or Egg-derived Influenza Vaccine
Description
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.
Time Frame
Up to 6 months postvaccination
Title
Geometric Mean Titers (GMTs) After One Dose of Cell Culture-derived or the Egg-derived Influenza Vaccine in Adult and Elderly Subjects
Description
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.
Time Frame
Day 22 postvaccination
Title
Geometric Mean Ratios (GMRs), After One Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine in Adult and Elderly Subjects
Description
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.
Time Frame
Day 22 postvaccination
Title
Percentages of Adult and Elderly Subjects Achieving HI Titers ≥ 40 After One Dose of the Cell Culture-derived or the Egg-derived Influenza Vaccine.
Description
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.
Time Frame
Day 22 postvaccination
Title
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.
Description
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.
Time Frame
Day 22 postvaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 18 to < 61 years of age (first age group) OR 61 years of age and older (second age group) at enrolment in V58P4 Mentally competent to understand the nature, the scope and the consequences of the study Able and willing to give written informed consent prior to study entry Available for all the visits scheduled in the study in good health as determined by: Medical history related to the previous six months, Physical examination, Clinical judgment of the investigator. Exclusion Criteria: Unwilling or unable to give written informed consent to participate in the study Currently experiencing an acute infectious disease Any serious disease such as, for example: Cancer (except for benign or localized skin cancer and non metastatic prostate cancer not currently treated with chemotherapy) Autoimmune disease (including rheumatoid arthritis) Advanced arteriosclerotic disease or complicated diabetes mellitus Chronic obstructive pulmonary disease (COPD) requiring oxygen therapy Acute or progressive hepatic disease Acute or progressive renal disease Congestive heart failure Surgery planned during the study period Bleeding diathesis History of hypersensitivity to any component of the study medication or chemically related substances, such as allergy to eggs or egg products Known or suspected impairment/alteration of immune function resulting from: Receipt of immunosuppressive therapy (any cortical steroid or cancer chemotherapy) Receipt of immunostimulants Receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within the past 3 months and for the full length of the study High risk for developing an immunocompromising disease History of drug or alcohol abuse Laboratory confirmed influenza disease in the past 6 months Received influenza vaccine within the past 6 months 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 Participation in another clinical trial within 90 days prior to enrollment and throughout the full length of the study 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 Pregnant/ breast feeding women or women who refuse to use a reliable contraceptive method during the first three weeks after vaccination Any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Vaccines and Diagnostics
Organizational Affiliation
Novartis Vaccines
Official's Role
Study Chair
Facility Information:
Facility Name
Wojewódzki Szpital Dzieci_cy
City
Ul. Langiewicza 2
State/Province
Kielce
ZIP/Postal Code
25-381
Country
Poland
Facility Name
Centrum Bada_ Farmakologii Klinicznej
City
Ul. Ujastek 3
State/Province
Krakow
ZIP/Postal Code
30-969
Country
Poland
Facility Name
NZOZ Jagiello_skie
City
Centrum Medyczne Sp. Z O.o., O_. Jagiello_skie 1
State/Province
Kraków
ZIP/Postal Code
31-832
Country
Poland
Facility Name
NZOZ Praktyka Grupowa Lekarzy Rodzinnych, "Familia" Sp. z o.o.
City
Pl. Sikorskiego 6a
State/Province
Kraków
ZIP/Postal Code
31-115
Country
Poland
Facility Name
Szpital Jana Pawła II, Oddz. Neuroinfekcji
City
Ul. Pr_dnicka 80
State/Province
Kraków
ZIP/Postal Code
31-202
Country
Poland

12. IPD Sharing Statement

Citations:
PubMed Identifier
22418809
Citation
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.
Results Reference
result

Learn more about this trial

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

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