Immunogenicity, Safety and Tolerability of a Trivalent Subunit Inactivated Vaccine in Healthy Subjects 50 Years and Above

September 29, 2014 updated by: Novartis

A Multi-Center, Phase IV, Randomized, Controlled, Observer Blind Study to Evaluate the Immunogenicity, Safety, and Tolerability of a Trivalent Subunit Inactivated Influenza Vaccine in Healthy Subjects Aged 50 Years and Above

Demonstrate non-inferiority of the post-vaccination (Day 22) Hemagglutination inhibition (HI) Geometric Mean Titers (GMTs) of trivalent, inactivated, subunit influenza vaccine (TIV) over the corresponding GMTs of the comparator vaccine for all three strains, in healthy adults aged 50 years and above.

Demonstrate non-inferiority of the percentages of subjects achieving seroconversion in antibody titers at Day 22 in the TIV group over the corresponding percentages of subjects in the comparator group for all three strains, in healthy adults aged 50 years and above.

Study Overview

Status

Completed

Conditions

Study Type

Interventional

Enrollment (Actual)

2902

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Benátky nad Jizerou
      • Kbel 163, Benátky nad Jizerou, Czech Republic, 294 71
        • Site 71 - Ordinace všeobecného lékaře
    • Hradec Kralove
      • Poliklinika II., Bratri Stefanu 895, Hradec Kralove, Czech Republic, 500 03
        • Site 70 - Vaccination and Travel Medicine Centre
    • Alabang Muntinlupa City
      • Filinvest Corporate City, Alabang Muntinlupa City, Philippines
        • Site 61 - Research Institute for Tropical Medicine DOH Compound
    • Cavite
      • Congressional Road, Dasmarinas City, Cavite, Philippines, 4114
        • Site 60 - De La Salle Health Sciences Institute, Room 6210 and 6206 De La Salle Angelo King Medical Research Center
    • Manila
      • Mesa, Manila, Philippines
        • Site 63 - Our Lady of Lourdes Hospital, 46 P. Sanchez Street, Sta.
    • Muntinlupa City
      • Alabang, Muntinlupa City, Philippines
        • Site 62 - Research Institute for Tropical Medicine DOH Compound, Filinvest Corporate City
    • Cape Town
      • Province of the Western Cape, Cape Town, South Africa, 7500
        • Site 33 - TREAD Research , Room 41, 8th Floor, Department of Cardiology, Tygerberg Hospital, Francie van Zijl Drive
      • Province of the Western Cape, Cape Town, South Africa, 7700
        • Site 43 - Allergy Diagnostic & Clinical Research Unit, UCT Lung Institute, George Street
      • Rondebosch, Cape Town, South Africa, 7700
        • Site 34 - Synopsis Research, Room 8, First floor, Fountain Centre, Belmont Road
      • Western Cape, Cape Town, South Africa, 7530
        • Site 41 - Tiervlei Trial Centre, Karl Bremer Hospital, c/o Mike Pienaar Boulevard & Frans Conradie Avenue, Bellville
    • Durban
      • Sydenham, Durban, South Africa, 4091
        • Site 45 - 343 Randles Road
    • Gauteng
      • Benoni, Gauteng, South Africa, 1511
        • Site 44 - Dr B van der Berg and Associates, 162 Pretoria Road, Rynfield
      • Boksburg North, Gauteng, South Africa, 1459
        • Site 31 - MD Search, 1 Paul Smit Street
      • Eloffsdal, Gauteng, South Africa, 0084
        • Site 32 - EMMED Research, Emmed Research, 641 5th Avenue
      • Lyttleton, Gauteng, South Africa, 0157
        • Site 35 - I Engelbrecht Research (Pty) Ltd, 174 Cradock Avenue
      • Midrand, Gauteng, South Africa, 1685
        • Site 36 - Midrand Medical Centre, Shop #1, Health Emporium, Cnr Church and Market Street
      • Sophiatown, Gauteng, South Africa, 2092
        • Site 39 - Medicross Sophiatown, Cnr Edward and Millar Streets
      • Soweto, Gauteng, South Africa, 1862
        • Site 38 - Perinatal HIV Research Unit, New Nurses Home, Chris Hani Baragwanath Academic Hospital, Chris Hani Road
    • George
      • York Street, George, South Africa, 6529
        • Site 37 - Excellentis Clinical Trial Consultants, Suite 201, York Building, 72
    • Johannesburg
      • Newtown, Johannesburg, South Africa, 2113
        • Site 40 - Newtown Clinical Research Centre, Suite 3, Newgate Centre, 104 Jeppe Street
    • Somerset West
      • Sir Lowry's Pass Road, Somerset West, South Africa, 7130
        • Site 46 - Helderberg Clinical Trials Centre, Suite 7G&H Arun Place
    • Bangkok
      • Bangkoknoi, Bangkok, Thailand, 10700
        • Site 53 - Clinical Trials Unit, Office for Research and Development, His Majesty the King's 80th Birthday December 2007 Building, 3rd floor, room 307, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Prannok Rd.
      • Rama 4 Rd., Pathumwan, Bangkok, Thailand, 10300
        • Site 52 - 1. Faculty of Medicine, Chulalongkorn University
      • Thai Red Cross Society, Rama 4 Rd., Pathumwan, Bangkok, Thailand, 10300
        • Site 52 - 2. Queen Saovabha Memorial Institute
    • Nayok
      • Ongkarak, Nakhorn, Nayok, Thailand, 26120
        • Site 51 - Faculty of Medicine, Srinakharinwirot University, HRH Princess, Sirindhorn Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Males and females aged 50 years and above, mentally competent, willing and able to give written informed consent prior to study entry and after the nature of the study has been explained according to local regulatory requirements.
  • Individuals able to comply with all the study requirements.
  • Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator.

Exclusion Criteria:

  • Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study.
  • Individuals with any progressive or severe neurologic disorder, seizure disorder or Guillain-Barré syndrome.
  • Individuals who are not able to comprehend and to follow all required study procedures for the whole period of the study.
  • Individuals who have received any seasonal or pandemic influenza vaccine or have had a laboratory confirmed seasonal or pandemic influenza disease within the past 6 months.
  • Individuals with history or any illness that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study.
  • Individuals with positive HIV test result, with history of an autoimmune disorder or any other known or suspected impairment /alteration of the immune system, or under immunosuppressive therapy within 6 months or use of any parenteral or oral corticosteroids within the previous 30 days.
  • Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
  • Individuals with any serious chronic or progressive disease according to judgment of the investigator (neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
  • Individuals who have any malignancy (excluding nonmelanotic skin cancer) or lymphoproliferative disorder.
  • Individuals with history of any anaphylactic adverse event and/or serious allergic adverse event following a vaccination, a proven hypersensitivity to any component of the study vaccine (eg, to eggs or eggs product as well as ovalbumin, chicken protein, chicken feathers, influenza viral protein, kanamycin and neomycin sulphate) or latex allergy.
  • Individuals participating in any clinical trial with another investigational product 30 days prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study.
  • Receipt of nonstudy vaccines (with the exception of post-exposure vaccination in a medical emergency, eg, hepatitis, rabies, tetanus) within 3 weeks prior to Visit 1.
  • Individuals who have ever received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation in the past 12 weeks.
  • Individuals who have received antibiotics within 6 days before vaccination.
  • Individuals with body temperature (axillary temperature) ≥38 degrees Celsius (≥ 100.4° F) within the last 3 days of intended study vaccination.
  • BMI > 35 kg/m2.
  • Female who are pregnant or nursing (breastfeeding) mothers or females of childbearing potential do not plan to use acceptable birth control measures, for the whole duration of the study. Adequate contraception is defined as hormonal (eg, oral, injection, transdermal patch, implant, cervical ring), barrier (eg, condom with spermicide or diaphragm with spermicide), intrauterine device (IUD), or monogamous relationship with vasectomized partner who has been vasectomized for 6 months or more prior to the subject's study entry; Abstinence.
  • Individuals who are part of study personnel or close family members conducting this study.
  • Individuals with history of substance or alcohol abuse within the past 2 years.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Agriflu
A single 0.5 mL dose of Investigational vaccine TIV (Agriflu) at visit 1, administered intramuscularly
Other Names:
  • Trivalent Influenza Virus Vaccine (purified surface antigen, inactivated, egg-derived)
Active Comparator: Fluvirin
A single 0.5 mL dose of control vaccine TIVf (Fluvirin) at visit 1, administered intramuscularly
Other Names:
  • Trivalent Influenza Virus Vaccine (purified surface antigen, inactivated, egg-derived)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hemagglutination Inhibition (HI) Geometric Mean Titers (GMTs) of TIV Group and TIVf Group for All Three Strains, in Healthy Adults Aged ≥50 Years
Time Frame: Day 22

Non-inferiority of Postvaccination Hemagglutination Inhibition (HI) Geometric Mean Titers (GMTs) of TIV (Trivalent Subunit Inactivated Influenza Vaccine) Group Over the Corresponding TIVf Group for All Three Strains, three weeks after vaccination (day 22).

The upper limit of the two-sided 95% confidence interval (CI) on the ratio of GMTs (GMT TIVf/GMT TIV) should not exceed the non-inferiority margin of 1.5.

Day 22
Percentages of Subjects Achieving Seroconversion (SC) in Antibody Titers in the TIV Group Compared With the Corresponding Percentages of Subjects in the TIVf Group for All Three Strains At Day 22, in Healthy Adults Aged ≥50 Years
Time Frame: Day 22

Non-Inferiority was measured as the percentages of subjects who achieved seroconversion in HI titers three weeks (day 22) after vaccination of TIV compared with TIVf, against each of three vaccine strains.

Seroconversion is defined as a prevaccination titer <10 and postvaccination HI ≥40 or as a prevaccination titer ≥10 and at minimum four-fold rise in postvaccination antibody titer.

The upper limit of the two-sided 95% CI on the difference between the seroconversion rates (Seroconversion TIVf - SeroconversionTIV) should not exceed 10%.

Day 22

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of Percentages of Subjects Who Achieved HI Seroconversion and HI Titer ≥1:40 Against Each of Three Strains After One Vaccination of TIV and TIVf Vaccine
Time Frame: Day 22

Percentage of subjects achieving HI seroconversion against each of three vaccine strains was measured three weeks after vaccination of TIV and TIVf vaccine (day 22).

Percentage of subjects who achieved HI titer ≥1:40 against each of three vaccine strains was measured three weeks after one vaccination of TIV and TIVf vaccine.

According to Center for Biologics Evaluation and Research recommendations (CBER 2007), the criterion for seroconversion is considered met if the lower limit of the two-sided 95% CI for the percentage of subjects with HI seroconversion is ≥40% (<65 years) or ≥30% (≥65 years).

As per the CBER criteria, the lower limit of the two-sided 95% CI for the percentage of subjects who achieved HI titer ≥ 1:40 should be ≥70% (<65 years) or ≥60% (≥65 years).

Day 22
Geometric Mean Ratio of Subjects Against Each of Three Strains After One Vaccination of TIV and TIVf Vaccine
Time Frame: Day 22
Geometric mean ratio (GMR) of subjects was calculated as the ratio of postvaccination to prevaccination HI GMTs against each of three vaccine strains, three weeks after vaccination of TIV and TIVf vaccine (day 22).
Day 22
Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV and TIVf
Time Frame: Day 1 to 7 postvaccination
Safety was assessed as the number of subjects who reported solicited local and systemic adverse events from day 1 up to and including day 7 after vaccination of TIV and control.
Day 1 to 7 postvaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Collaborators

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2013

Primary Completion (Actual)

December 1, 2013

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

May 29, 2013

First Submitted That Met QC Criteria

May 31, 2013

First Posted (Estimate)

June 3, 2013

Study Record Updates

Last Update Posted (Estimate)

October 1, 2014

Last Update Submitted That Met QC Criteria

September 29, 2014

Last Verified

September 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Influenza

Clinical Trials on Agriflu (TIV)

3
Subscribe