Safety and Immunogenicity of MF59C.1 Adjuvanted Trivalent Subunit Influenza Vaccine in Elderly Subjects

Influenza Clinical Trial

Official title:

A Phase III, Randomized, Controlled, Observer-Blind, Multicenter Study to Evaluate the Safety and Immunogenicity and the Consistency of Three Consecutive Lots of a MF59C.1 Adjuvanted Trivalent Subunit Influenza Vaccine in Elderly Subjects Aged 65 Years and Older

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01162122
• Other study ID #: V70_27
• Status: Completed
• Phase: Phase 3
• First received: July 13, 2010
• Last updated: June 16, 2014
• Start date: August 2010
• Est. completion date: November 2011

Study information

• Verified date: June 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The present phase III study aims to evaluate the safety and immunogenicity of MF59-adjuvanted subunit seasonal influenza vaccine and to evaluate the consistency in the manufacturing process of three consecutive lots of MF59-adjuvanted subunit seasonal influenza vaccine with respect to immunogenicity in subjects aged 65 years and older. The active comparator non-adjuvanted seasonal influenza vaccine is approved for use in this age group in the United States and will be used to provide a comparative assessment for immunogenicity and safety.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7109
• Est. completion date: November 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

Males and females subjects aged =65 years at day of vaccination who are willing and able to comply to study procedures.

Exclusion Criteria:

1. Individuals with behavioral or cognitive impairment or a psychiatric condition or with a history of any illness that,in the opinion of the investigator, would have interfered with the subject's ability to participate in the study.

2. Individuals who were not able to comprehend and/or follow all required study procedures for the whole period of the study.

3. Known or suspected impairment/alteration of immune function.

4. Individuals with a known bleeding diathesis.

5. History of Guillain-Barré syndrome.

6. Individuals with history of allergy to vaccine components and/or a history of any anaphylaxis, serious vaccine reactions or hypersensitivity to influenza viral proteins, egg proteins (including ovalbumin), polymyxin, neomycin, betapropiolactone, thimerosal/ sodium ethylmercurothiosalicylate/ mercury and nonylphenolethoxylate/ nonoxynol-9 (spermicide).

7. Receipt of another investigational agent within 30 days prior to enrollment in the study or before completion of the safety follow-up period in another study.

8. Individuals who had received any other vaccines within 2 weeks for inactivated vaccines or 4 weeks for live vaccines prior to enrollment in this study or who had planned to receive any vaccine within 3 weeks from the study vaccine.

9. Individuals who had received vaccination against seasonal influenza in the previous 6 months.

10. Individuals with oral temperature =38.0°C (=100.4°F) on day of study vaccination.

11. Individuals with history of substance or alcohol abuse within the past 2 years.

12. Individuals providing consent who did not consent to the retention of their serum samples after study completion.

13. Elective surgery or hospitalization planned to occur during the treatment phase or during the follow-up phase that, according to the opinion of the investigator, might have poses additional risk to the subject.

14. Subjects from whom blood could not be drawn at visit 1.

Study Design

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

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Biological:
• MF59 adjuvanted trivalent subunit influenza vaccine (aTIV)
one dose 0.5 mL administered IM in the deltoid muscle of (preferably) the non-dominant arm
• Non-adjuvanted trivalent subunit influenza vaccine (TIV)
one 0.5 mL dose administered IM in the deltoid muscle of (preferably) the non-dominant arm

Locations

Country	Name	City	State
Colombia	209, Centro de Investigacion CAFAM	Avenida Carrera 68	Bogota
Colombia	206, Centro de Atencion e Investigacion Medica CAIMED	Carrera 42A	Bogota
Colombia	213, Centro de Atencion e Investigacion Medica CAIMED	Carrera 42A	Bogota
Colombia	207, Centro de Investigacion Cafesalud Medicina Prepagada	Cra 14 No Piso Sexto	Bogota
Panama	203, Health Research International HRI	Clayton ciudad del Saber Edificio 118
Panama	205, Medical and Research Center Calle 53 Urbanizacion Marbella	Consultorios Royal Center 108
Philippines	108, City Health Office 1 Rosa City	City Health Office 1	Rosa City
Philippines	101, Asian Hospital and Medical Center 2205 Civic Drive Filinvest	Corporate City Alabang	Muntinlupa
Philippines	109, Research Institute for Tropical Medicine Department of Health Compound FILINVEST	Corporate City Alabang	Muntinlupa
Philippines	103, De La Salle Health Sciences Institute	DBB B Dasmarinas	Cavite
Philippines	102, De La Salle Health Sciences Institute	Dbbb Dasmarinas	Cavite
Philippines	105, Manila Doctors Hospital, 667 United Nations Avenue	Ermita	Manila
Philippines	106, Our Lady of Lourdes Hospital, 46 P. Sanchez Street Sta.	Mesa	Manila
Philippines	110, San Juan de Dios Hospital, 2772 Roxas Blvd	Pasay City
Philippines	111, St Lukes Medical Center, 279 E Rodriguez Sr Boulevard	Quezon City
Philippines	104 Jose Reyes Memorial Medical Center	Rizal Avenue Avenida Cruz	Manila
Philippines	107 Philippine General Hospital	Taft Avenue	Manila
United States	318 Avail Clinical Research, 860 Peachwood Drive	Deland	Florida
United States	311 Regional Clinical Research INC, 415 Hooper Road	Endwell	New York
United States	323 PI Coor Clinical Research LCC, 10721 Main St Suite 1500	Fairfax	Virginia
United States	303 Prestige Clinical Research, 333 Conover Drive	Franklin	Ohio
United States	306 Westside Center for Clinical Research, 810 Lane Avenue South	Jacksonville	Florida
United States	321 Jordan River Family Medicine, 1868 West 9800 South Ste 100	Jordan	Utah
United States	313 Clinical Research Center of Nevada, 7425 W Azure Suite 150	Las Vegas	Nevada
United States	320 Johnson County Clin-Trials, 15602 College Blvd	Lenexa	Kansas
United States	328 Miami Research Associates, 6141 Sunset Drive	Miami	Florida
United States	316 Heartland Research Associates LLC - Axtell Clinic - PA, 700 Medical Center Dr	Newton	Kansas
United States	301, Tatum Highlands Medical Associates PLLC, 26224 N Tatum Blvd 15A	Phoenix	Arizona
United States	326 Triangle Medical Research, 5816 Creedmoor Rd. Suite 104	Raleigh	North Carolina
United States	314 Saint Louis Univ Med Div of Infectious Diseases Immunology, 1100 S Grand Blvd DRC- Rm 827	Saint Louis	Missouri
United States	330 Mercy Health Research, 12680 Olive Blvd Suite 200	Saint Louis	Missouri
United States	305 Foothill Family Clinic South, 6360 South 3000 East	Salt Lake City	Utah
United States	317 J. Lewis Research Inc., 2295 Foothill Drive	Salt Lake City	Utah
United States	312 Spartanburg Regional Medical Center, 485 Simuel Road	Spartanburg	South Carolina
United States	325 Omega Medical Research, 400 Bald Hill Road	Warwick	Rhode Island
United States	310 Heartland Research Associates LLC, 3730 N Ridge Road Suite 600	Wichita	Kansas
United States	322 Heartland Research Associates Wichita, 1709 S. Rock Road	Wichita	Kansas
United States	332 Piedmont Medical Research, 1901 S. Hawthorne Rd. Suite 306	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Vaccines

Countries where clinical trial is conducted

United States,  Colombia,  Panama,  Philippines, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Geometric Mean Titers in Subjects After Receiving One Dose of Lot 1 or Lot 2 or Lot 3 of aTIV	Immunologic equivalence of 3 consecutive production lots of aTIV (Lot 1, Lot 2 and Lot 3), was assessed in terms of Hemagglutination Inhibition (HI) Geometric Mean Titers (GMTs) in subjects, at three weeks after vaccination, against each vaccine strain.	Day 22 post vaccination	No
Primary	Comparison of aTIV Versus TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains - PPS	The non-inferiority of HI antibody responses of aTIV compared to TIV assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains.	Day 22 post vaccination	No
Primary	Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS	The non-inferiority of HI antibody responses of aTIV compared to TIV assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the three homologous vaccine strains.; Seroconversion defined as prevaccination HI titer <10 and postvaccination HI titer =40 or at least a 4-fold increase in HI titers from prevaccination HI titer =10.	Day 22 post vaccination	No
Primary	Comparison of aTIV Versus TIV in Terms of GMTs Against Homologous Strains-Full Analysis Set (FAS)	The superiority of HI antibody responses of aTIV compared to TIV assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains.	Day 22 post vaccination	No
Primary	Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS	The superiority of HI antibody responses of aTIV compared to TIV assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the three homologous vaccine strains.; Seroconversion defined as prevaccination HI titer <10 and postvaccination HI titer =40 or at least a 4-fold increase in HI titers from prevaccination HI titer =10.	Day 22 post vaccination	No
Primary	Percentage of Subjects With HI Titers =40 Against Homologous Strains	The percentage of subjects demonstrating HI titers =40, in overall group and in subjects with pre-defined co-morbidities (high risk group), against homologous strains, three weeks after vaccination with aTIV or TIV.	Day 22 post vaccination	No
Primary	Percentage of Subjects Achieving Seroconversion in HI Titers, Against Homologous Strains	The percentage of subjects achieving seroconversion in HI titers from baseline, in overall group and in subjects with pre-defined co-morbidities (high risk group), against homologous strains, three weeks after vaccination with aTIV or TIV.; Seroconversion is defined as prevaccination HI titer <10 and postvaccination HI titer =40 or at least a 4-fold increase in HI titers from prevaccination HI titer =10.	Day 22 post vaccination	No
Primary	Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains	The GMR of post-vaccination versus pre-vaccination HI titers (day 22/day 1) in overall group and in subjects with pre-defined co-morbidities (high risk group), against homologous strains, three weeks after vaccination with aTIV or TIV.	Day 22 post vaccination	No
Primary	Percentage of Subjects With HI Titers =40 Against Heterologous Strains	The percentage of subjects demonstrating HI titers =40, in overall group and in subjects with pre-defined co-morbidities (high risk group), against heterologous strains, three weeks after vaccination with aTIV or TIV.	Day 22 post vaccination	No
Primary	Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers, Against Heterologous Strains	The GMR of post-vaccination versus pre-vaccination HI titers (day 22/day 1) in overall group and in subjects with pre-defined co-morbidities (high risk group), against heterologous strains, three weeks after vaccination with aTIV or TIV.	Day 22 post vaccination	No
Primary	Percentage of Subjects Achieving Seroconversion in HI Titers, Against Heterologous Strains	The percentage of subjects achieving seroconversion in HI titers from baseline, in overall group and in subjects with pre-defined co-morbidities (high risk group), against heterologous strains, three weeks after vaccination with aTIV or TIV.; Seroconversion is defined as prevaccination HI titer <10 and postvaccination HI titer =40 or at least a 4-fold increase in HI titers from prevaccination HI titer =10.	Day 22 post vaccination	No
Secondary	Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-PPS	The non-inferiority of HI antibody responses of ATIV compared to TIV, in subjects with pre-defined co-morbidities (high risk subjects), was assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains.	Day 22 post vaccination	No
Secondary	Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-PPS	The non-inferiority of HI antibody responses of ATIV compared to TIV, in subjects with pre-defined co-morbidities (high risk group), assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the homologous vaccine strains.; Seroconversion is defined as prevaccination HI titer <10 and postvaccination HI titer =40 or at least a 4-fold increase in HI titers from prevaccination HI titer =10.	Day 22 post vaccination	No
Secondary	Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-FAS	The superiority of HI antibody responses of aTIV compared to TIV, in subjects with predefined co-morbidities (high risk group) assessed in terms of post vaccination GMTs at three weeks after vaccination against the three homologous vaccine strains.	Day 22 post vaccination	No
Secondary	Comparison of HI Antibody Responses of aTIV Versus TIV, in High Risk Group in Terms of Percentage of Subjects Achieving Seroconversion Against Homologous Strains-FAS	The superiority of HI antibody responses of aTIV compared to TIV, in subjects with pre-defined co-morbidities (high risk group), assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination against the homologous vaccine strains.; Seroconversion is defined as prevaccination HI titer <10 and postvaccination HI titer =40 or at least a 4-fold increase in HI titers from prevaccination HI titer =10.	Day 22 postvaccination	No
Secondary	Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS	The non-inferiority of HI antibody responses of aTIV compared to TIV against the heterologous vaccine strains, in overall group and in subjects with pre-defined co-morbidities (high risk subjects), was assessed in terms of post vaccination GMTs at three weeks after vaccination .	Day 22 post vaccination	No
Secondary	Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-FAS	The superiority of HI antibody responses of aTIV compared to TIV against the heterologous vaccine strains, in overall group and in subjects with pre-defined co-morbidities (high risk subjects), was assessed in terms of post vaccination GMTs at three weeks after vaccination.	Day 22 post vaccination	No
Secondary	Comparison of HI Antibody Responses of aTIV Versus TIV, in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-PPS	The non-inferiority of HI antibody responses of aTIV compared to TIV against the heterologous strains, in overall group and in subjects with pre-defined co-morbidities (high risk group), assessed in terms of percentage of subjects achieving seroconversion at three weeks after vaccination.; Seroconversion is defined as prevaccination HI titer <10 and postvaccination HI titer =40 or at least a 4-fold increase in HI titers from prevaccination HI titer =10.	Day 22 postvaccination	No
Secondary	Comparison of aTIV Versus TIV in Terms of Percentage of Subjects Achieving Seroconversion Against Heterologous Strains-FAS	The superiority of HI antibody responses of aTIV compared to TIV against the heterologous vaccine strains, in overall group and in subjects with pre-defined co-morbidities (high risk subjects), was assessed in terms of percentage of subjects achieving seroconversion, at three weeks after vaccination.; Seroconversion is defined as prevaccination HI titer <10 and postvaccination HI titer =40 or at least a 4-fold increase in HI titers from prevaccination HI titer =10.	Day 22 post vaccination	No
Secondary	Persistence of GMTs Against Homologous and Heterologous Strains	The GMTs against homologous and heterologous strains, persisting in subjects at six months (day 181) and one year (day 366) after vaccination with either aTIV or TIV.	Day 181, Day 366 post vaccination	No
Secondary	Percentage of Subjects With Seroconversion Upto One Year After Vaccination, Against Homologous and Heterologous Strains	The percentage of subjects demonstrating seroconversion in HI titers against homologous and heterologous strains, at six months (day 181) and one year (day 366) after vaccination with either aTIV or TIV.; Seroconversion is defined as prevaccination HI titer <10 and postvaccination HI titer =40 or at least a 4-fold increase in HI titers from prevaccination HI titer =10.	Day 181, Day 366 post vaccination	No
Secondary	Number of Subjects Reporting Influenza Like Illness (ILI) Across Vaccine Groups	The number of subjects reporting ILI from three weeks after vaccination to up to one year in aTIV group compared to TIV group, by country.	Day 22 through Day 366 post vaccination	No
Secondary	Number of High Risk Subjects With Exacerbation of Preexisting Chronic Disease, Across Vaccine Groups	The number of high risk subjects reporting exacerbation of preexisting chronic conditions (i.e.congestive heart failure, Chronic Obstructive Pulmonary disease (COPD), asthma, hepatic disease, renal insufficiency, and neurological/neuromuscular or metabolic disorders including diabetes mellitus) in aTIV group compared to TIV group.	Day 1 through Day 366 post vaccination	No
Secondary	Number of Subjects Reporting Healthcare Utilization Across Vaccine Groups	The number of subjects with emergency room visits, unscheduled physician visits, and hospitalizations due to community acquired influenza or pneumonia, cardiopulmonary disease, cardiac disease, respiratory or pulmonary disease,in aTIV group compared to TIV group.	Day 1 through Day 366 post vaccination	No
Secondary	All Cause Mortality Rate, Across Vaccine Groups	The all-cause mortality rate (excluding injury)reported in aTIV group compared to TIV group, by country.	Day 1 through Day 366 post vaccination	No
Secondary	Number of Subjects Reporting Solicited Adverse Events Following Vaccination	The number of subjects reporting solicited local and systemic adverse events and other adverse events in aTIV group compared to TIV group.	Day 1 through Day 7 post vaccination	Yes