Safety and Immunogenicity of a Cell Culture-derived Influenza Vaccine in Healthy Adults and Elderly

• ClinicalTrials.gov Identifier: NCT00492063
• Recruitment Status: Completed
• First Posted: June 27, 2007
• Results First Posted: February 21, 2013
• Last Update Posted: January 1, 2016
• Sponsor: Novartis Vaccines
• Information provided by (Responsible Party): Novartis ( Novartis Vaccines )

Study Description

Brief Summary:

The present study aims to evaluate the safety and immunogenicity of the new influenza subunit vaccine produced in Madin Darby Canine Kidney (MDCK) cells in healthy adult and elderly subjects.

Condition or disease	Intervention/treatment	Phase
Influenza	Biological: Cell culture-derived trivalent subunit influenza vaccine (cTIV); Biological: Egg-derived trivalent subunit influenza vaccine (TIV)	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2654 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: A Phase III, Observer-Blind, Randomized, Multi-Center Study to Evaluate Safety, Tolerability and Immunogenicity of a Single Intramuscular Dose of a Trivalent Subunit Influenza Vaccine Produced in Mammalian Cell Culture and of a Trivalent Subunit Influenza Vaccine Produced in Embryonated Hen Eggs, in Healthy Adult and Elderly Subjects
• Study Start Date: September 2004
• Actual Primary Completion Date: December 2004
• Actual Study Completion Date: May 2005

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cell culture-derived influenza vaccine (cTIV)	Biological: Cell culture-derived trivalent subunit influenza vaccine (cTIV); One vaccination (0.5 mL) of cell culture-derived influenza vaccine (cTIV) was administered in the deltoid muscle
Active Comparator: Egg-derived influenza virus vaccine (TIV)	Biological: Egg-derived trivalent subunit influenza vaccine (TIV); One vaccination (0.5 mL) of egg-derived influenza virus vaccine (TIV) was administered in the deltoid muscle

Outcome Measures

Primary Outcome Measures :

1. Percentages Of Subjects Who Achieved HI Titer ≥40 After One Vaccination of Cell Culture-derived (cTIV) or Egg-derived (TIV) Influenza Subunit Vaccines [ Time Frame: Before vaccination (day 1) and three weeks after vaccination (day 22) ]

   Immunogenicity was measured as the percentage of adults (≥18 to ≤60 years) and elderly (≥61 years) achieving HI titers ≥40 at baseline (day 1) and three weeks (day 22) after one vaccination of cTIV or TIV vaccine for each of three vaccine strains, evaluated using the hemagglutination inhibition (HI) egg-derived antigen assay.

   In compliance with the requirements of the EMEA recommendations (CPMP/BWP/2490/00, CPMP/BWP/214/96), this criterion is met if the percentage of subjects achieving HI titers ≥40 is >70% in the ≥18 to ≤60 years of age group or >60% in the ≥61 years of age group.

2. Percentages Of Subjects Who Achieved Seroconversion Or Significant Increase In HI Titer After One Vaccination of cTIV or TIV [ Time Frame: Three weeks after vaccination (day 22) ]
   Seroconversion or significant in HI titer is defined as the percentage of subjects with a prevaccination HI titer <10 (negative) to a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, at least a 4-fold increase in postvaccination HI titer. In compliance with the requirements of the EMEA recommendations (CPMP/BWP/2490/00, CPMP/BWP/214/96), the criterion is met if the percentage of subjects achieving seroconversion/significant increase is >40% in the ≥18 to ≤60 years of age group or >30% in the ≥61 years of age group.
3. Geometric Mean Ratio of Subjects After One Vaccination of cTIV or TIV [ Time Frame: Three weeks after vaccination (day 22) ]
   Immunogenicity was measured as the geometric mean ratio (GMR), calculated as the ratio of postvaccination to prevaccination HI Geometric Mean Titers (GMTs), three weeks after (day 22) one vaccination of cTIV or TIV. In compliance with the requirements of the EMEA recommendations (CPMP/BWP/2490/00, CPMP/BWP/214/96), this criterion is met if the GMR (day 22/day 1) in HI antibody titer is >2.5 in the ≥18 to ≤60 years of age group or >2.0 in the ≥61 years of age group.

Secondary Outcome Measures :

1. Number of Subjects Who Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination [ Time Frame: Up to 7 days postvaccination ]
   The solicited local and systemic reactions were collected from day 1 up to and including day 7 after vaccination for both the vaccine groups.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. 18 to 60 years of age (first age group) OR over 60 years of age (second age group)
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. residence in the study area

6. in good health as determined by:

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

Exclusion Criteria:

1. unable or unwilling to give written informed consent to participate in the study
2. suffering from an acute infectious disease

3. any serious disease such as:

   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 within the past 6 months
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 planned vaccination within 3 weeks following the study vaccination
12. any acute respiratory disease or infections requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis was acceptable) or experienced fever ≥ 38°C within the past 3 days
13. pregnant women or women who refused to use a reliable contraceptive method throughout the study (180 days)
14. any condition which, in the opinion of the investigator, might have interfered with the evaluation of the study objectives.

Contacts and Locations

Locations

Poland

Wojewódzki Szpital Dzieciecy

ul. Langiewicza 2, Kielce, Poland, 25-381

N ZOZ Jagiellonskie, Centrum Medyczne Sp. z o.o.

os. Jagiellonskie 1, Kraków, Poland, 31-832

Praktyka Grupowa Lekarzy POZ "Familia"

Pl. Sikorskiego 6a, Kraków, Poland, 31-115

Szpital Jana Pawła II

ul. Pradnicka 80, Kraków, Poland, 31-202

Centrum Farmakologii Klinicznej

Krakow, Poland, 30-969

Sponsors and Collaborators

Novartis Vaccines

Investigators

• Study Chair: Novartis Vaccines; Novartis Vaccines

More Information

Publications of Results:

Szymczakiewicz-Multanowska A, Groth N, Bugarini R, Lattanzi M, Casula D, Hilbert A, Tsai T, Podda A. Safety and immunogenicity of a novel influenza subunit vaccine produced in mammalian cell culture. J Infect Dis. 2009 Sep 15;200(6):841-8. doi: 10.1086/605505. Erratum in: J Infect Dis. 2009 Dec 1;200(11):1801-2.

• Responsible Party: Novartis Vaccines
• ClinicalTrials.gov Identifier: NCT00492063
• Other Study ID Numbers: V58P4
• First Posted: June 27, 2007
• Results First Posted: February 21, 2013
• Last Update Posted: January 1, 2016
• Last Verified: December 2015

Keywords provided by Novartis ( Novartis Vaccines ):

safety; immunogenicity; non-inferiority; MDCK; cell culture-derived; subunit influenza vaccine; influenza prevention

Additional relevant MeSH terms:

Influenza, Human; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs