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

NCT01162122 | Completed Phase 3 Results

• 1 other identifier: V70_27
• Study Type: interventional
• Target: 7,109
• Locations: 4 countries
• Sites: 38

Brief 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.

Conditions

Influenza

Keywords

Elderly; Influenza; Immunogenicity; Safety; Adjuvant; Adjuvanted; Adjuvants; Vaccines

Outcome Measures

Primary Outcomes (11)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

Secondary Outcomes (15)

• Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-PPS

  Day 22 post vaccination

• 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

  Day 22 post vaccination

• Comparison of aTIV Versus TIV in High Risk Group in Terms of GMTs Against Homologous Strains-FAS

  Day 22 post vaccination

• 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

  Day 22 postvaccination

• Comparison of aTIV Versus TIV in Terms of GMTs Against Heterologous Strains-PPS

  Day 22 post vaccination

Study Arms (2)

aTIV

EXPERIMENTAL

Subjects received one dose of MF59-adjuvanted trivalent subunit influenza vaccine (aTIV) from one of three consecutive lots (Lot 1, Lot 2 or Lot 3).

Biological: MF59 adjuvanted trivalent subunit influenza vaccine (aTIV)

Licensed TIV

EXPERIMENTAL

Subjects received one dose of non-adjuvanted trivalent subunit influenza vaccine (TIV).

Biological: Non-adjuvanted trivalent subunit influenza vaccine (TIV)

Interventions

MF59 adjuvanted trivalent subunit influenza vaccine (aTIV) BIOLOGICAL

one dose 0.5 mL administered IM in the deltoid muscle of (preferably) the non-dominant arm

Also known as: Fluad

aTIV

Non-adjuvanted trivalent subunit influenza vaccine (TIV) BIOLOGICAL

one 0.5 mL dose administered IM in the deltoid muscle of (preferably) the non-dominant arm

Also known as: Agriflu

Licensed TIV

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.
• Individuals who were not able to comprehend and/or follow all required study procedures for the whole period of the study.
• Known or suspected impairment/alteration of immune function.
• Individuals with a known bleeding diathesis.
• History of Guillain-Barré syndrome.
• 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).
• 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.
• 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.
• Individuals who had received vaccination against seasonal influenza in the previous 6 months.
• Individuals with oral temperature ≥38.0°C (≥100.4°F) on day of study vaccination.
• Individuals with history of substance or alcohol abuse within the past 2 years.
• Individuals providing consent who did not consent to the retention of their serum samples after study completion.
• 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.
• Subjects from whom blood could not be drawn at visit 1.

Sponsors & Collaborators

• Novartis Vaccines: lead

Study Sites (38)

301, Tatum Highlands Medical Associates PLLC, 26224 N Tatum Blvd 15A

Phoenix, Arizona, 85253, United States

Location

318 Avail Clinical Research, 860 Peachwood Drive

DeLand, Florida, 32720, United States

Location

306 Westside Center for Clinical Research, 810 Lane Avenue South

Jacksonville, Florida, 32205, United States

Location

328 Miami Research Associates, 6141 Sunset Drive

Miami, Florida, 33143, United States

Location

320 Johnson County Clin-Trials, 15602 College Blvd

Lenexa, Kansas, 66219, United States

Location

316 Heartland Research Associates LLC - Axtell Clinic - PA, 700 Medical Center Dr

Newton, Kansas, 67114, United States

Location

310 Heartland Research Associates LLC, 3730 N Ridge Road Suite 600

Wichita, Kansas, 67205, United States

Location

322 Heartland Research Associates Wichita, 1709 S. Rock Road

Wichita, Kansas, 67207, United States

Location

314 Saint Louis Univ Med Div of Infectious Diseases Immunology, 1100 S Grand Blvd DRC- Rm 827

St Louis, Missouri, 63104, United States

Location

330 Mercy Health Research, 12680 Olive Blvd Suite 200

St Louis, Missouri, 63141, United States

Location

313 Clinical Research Center of Nevada, 7425 W Azure Suite 150

Las Vegas, Nevada, 89130, United States

Location

311 Regional Clinical Research INC, 415 Hooper Road

Endwell, New York, 13760, United States

Location

326 Triangle Medical Research, 5816 Creedmoor Rd. Suite 104

Raleigh, North Carolina, 27612, United States

Location

332 Piedmont Medical Research, 1901 S. Hawthorne Rd. Suite 306

Winston-Salem, North Carolina, 27103, United States

Location

303 Prestige Clinical Research, 333 Conover Drive

Franklin, Ohio, 45005, United States

Location

325 Omega Medical Research, 400 Bald Hill Road

Warwick, Rhode Island, 02886, United States

Location

312 Spartanburg Regional Medical Center, 485 Simuel Road

Spartanburg, South Carolina, 29303, United States

Location

321 Jordan River Family Medicine, 1868 West 9800 South Ste 100

Jordan, Utah, United States

Location

317 J. Lewis Research Inc., 2295 Foothill Drive

Salt Lake City, Utah, 84109, United States

Location

305 Foothill Family Clinic South, 6360 South 3000 East

Salt Lake City, Utah, 84121, United States

Location

323 PI Coor Clinical Research LCC, 10721 Main St Suite 1500

Fairfax, Virginia, 22030, United States

Location

209, Centro de Investigacion CAFAM

Avenida Carrera 68, Bogota D.C., Colombia

Location

206, Centro de Atencion e Investigacion Medica CAIMED

Carrera 42A, Bogota D.C., 1750, Colombia

Location

213, Centro de Atencion e Investigacion Medica CAIMED

Carrera 42A, Bogota D.C., 1750, Colombia

Location

207, Centro de Investigacion Cafesalud Medicina Prepagada

Cra 14 No Piso Sexto, Bogota D.C., Colombia

Location

203, Health Research International HRI

Clayton Ciudad Del Saber Edificio 118, Provincia de Panamá, Panama

Location

205, Medical and Research Center Calle 53 Urbanizacion Marbella

Consultorios Royal Center 108, Provincia de Panamá, Panama

Location

103, De La Salle Health Sciences Institute

DBB B Dasmarinas, Cavite, 4114, Philippines

Location

102, De La Salle Health Sciences Institute

Dbbb Dasmarinas, Cavite, 4114, Philippines

Location

105, Manila Doctors Hospital, 667 United Nations Avenue

Ermita, Manila, 1000, Philippines

Location

106, Our Lady of Lourdes Hospital, 46 P. Sanchez Street Sta.

Mesa, Manila, 1016, Philippines

Location

104 Jose Reyes Memorial Medical Center

Rizal Avenue Avenida Cruz, Manila, 1003, Philippines

Location

107 Philippine General Hospital

Taft Avenue, Manila, 1000, Philippines

Location

101, Asian Hospital and Medical Center 2205 Civic Drive Filinvest

Corporate City Alabang, Muntinlupa, 1781, Philippines

Location

109, Research Institute for Tropical Medicine Department of Health Compound FILINVEST

Corporate City Alabang, Muntinlupa, Philippines

Location

108, City Health Office 1 Rosa City

City Health Office 1, Rosa City, 4026, Philippines

Location

110, San Juan de Dios Hospital, 2772 Roxas Blvd

Pasay, 1300, Philippines

Location

111, St Lukes Medical Center, 279 E Rodriguez Sr Boulevard

Quezon City, 1102, Philippines

Location

Related Publications (1)

• Frey SE, Reyes MR, Reynales H, Bermal NN, Nicolay U, Narasimhan V, Forleo-Neto E, Arora AK. Comparison of the safety and immunogenicity of an MF59(R)-adjuvanted with a non-adjuvanted seasonal influenza vaccine in elderly subjects. Vaccine. 2014 Sep 3;32(39):5027-34. doi: 10.1016/j.vaccine.2014.07.013. Epub 2014 Jul 18.

  PMID: 25045825 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

fluad vaccine; Influenza Vaccines

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Posting Director
• Organization: Novartis Vaccines and Diagnostics

RegistryContactVaccinesUS@novartis.com

Study Officials

• Novartis Vaccines

  Novartis Vaccines

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2010
• First Posted: July 14, 2010
• Study Start: August 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: November 1, 2011
• Last Updated: June 26, 2014
• Results First Posted: June 12, 2014

Record last verified: 2014-06

Locations

US (21); PA (2); CO (4); PH (11)