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

Influenza Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01867021
• Other study ID #: V71_22
• Status: Completed
• Phase: Phase 4
• First received: May 29, 2013
• Last updated: September 29, 2014
• Start date: May 2013
• Est. completion date: December 2013

Study information

• Verified date: September 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationThailand: Food and Drug AdministrationPhilippines : Food and Drug AdministrationCzech Republic: State Institute for Drug ControlSouth Africa: Medicines Control Council
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2902
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 50 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Biological:
• Fluvirin(TIVf)

• Agriflu (TIV)

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Novartis	Novartis Vaccines

Countries where clinical trial is conducted

Czech Republic,  Philippines,  South Africa,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hemagglutination Inhibition (HI) Geometric Mean Titers (GMTs) of TIV Group and TIVf Group for All Three Strains, in Healthy Adults Aged =50 Years	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	No
Primary	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	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	No
Secondary	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	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	No
Secondary	Geometric Mean Ratio of Subjects Against Each of Three Strains After One Vaccination of TIV and TIVf Vaccine	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	No
Secondary	Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After One Vaccination of TIV and TIVf	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	Yes