Comparison of the Immunogenicity, Safety and Reactogenicity of FluBlok, To a Licensed Vaccine In Elderly Adults

Comparison of the Immunogenicity, Safety and Reactogenicity of FluBlok, Trivalent Recombinant Baculovirus-Expressed Hemagglutinin Influenza Vaccine, to a Licensed Egg-Grown Influenza Vaccine In Ambulatory Elderly Adults

The purpose of this study were to obtain additional evidence in support of the safety and immunogenicity of a recombinant hemagglutinin (rHA) vaccine in an elderly population, and to establish non-inferiority of the immunogenicity of the rHA vaccine when compared with a licensed trivalent influenza vaccine (TIV). Another purpose was to provide a preliminary estimate of the relative efficacy of the two vaccines against culture-positive influenza-like illness during the subsequent epidemic.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Influenza Vaccination

Detailed Description

Annual influenza epidemics are associated with serious excess morbidity and mortality, particularly among the elderly. Licensed trivalent inactivated influenza vaccines (TIVs) have been shown to reduce hospitalization and death following influenza in this vulnerable population, but their efficacy is lower than that observed in younger, healthy populations. In addition, recent studies have questioned the level of effectiveness of TIV in the elderly, suggesting that cohort studies have overestimated the benefits of immunization with current TIV formulations in this age group. In view of these considerations, it is widely accepted that improved and alternative vaccines are needed for control of seasonal and pandemic influenza.

Currently available TIVs are prepared from viruses that are grown in embryonated hens' eggs. Alternative substrates for vaccine production are desirable in order to reduce the vulnerability of and to expand influenza vaccine supply. Recombinant DNA techniques allow for expression of the influenza hemagglutinin (rHA) by baculovirus vectors in insect cell cultures. Advantages of this technique include speed of production, absence of egg protein, and a highly purified product. Previous studies among healthy younger and older adults have confirmed that rHA vaccines are safe, well tolerated and immunogenic at dosages up to nine times higher than those contained in TIV. Dose-related increases in serum antibody levels after immunization also were observed.

• Study Type: Interventional
• Enrollment (Actual): 870
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Center of Vaccine Development, Univ. of Maryland
    • Baltimore, Maryland, United States, 21230
      • Passport Health Maryland
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic College of Medicine
  • New Jersey
    • Shrewsbury, New Jersey, United States, 07702
      • Passport Health New Jersey
  • New York
    • Rochester, New York, United States, 14642
      • Rochester Medical Center
  • Pennsylvania
    • Pittsburg, Pennsylvania, United States, 15241
      • Primary Physicians Research
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ambulatory adults aged 65 and older
• Medically stable, as determined by oral temperature <100.0°F, medical history, and targeted physical examination based on medical history
• Able to understand and comply with planned study procedures
• Provides written informed consent prior to initiation of any study procedure.

Exclusion Criteria:

• Known allergy to eggs or other vaccine components.
• Immunosuppression as a result of an underlying illness or treatment, or used anticancer chemotherapy or radiation therapy within the preceding 36 months.
• Any malignancy (excluding nonmelanotic skin cancer or lymphoproliferative disorder), other than localized prostrate cancer, diagnosed or treated actively during the past 5 years. Subjects with any history of lymphoproliferative disorder will be excluded, while subjects with a history of localized nonmelanotic skin cancer may be eligible.
• Long-term use of oral steroids, parenteral steroids, or high-dose inhaled steroids within the preceding 6 months (Nasal and topical steroids are allowed).
• Major psychiatric diagnosis including schizophrenia, bipolar disease or other major depression, or any diagnosis of dementia or associated concomitant medications (e.g., Aricept) used for treating dementia
• History of receiving immunoglobulin or other blood product within the 3 months prior to enrollment in this study.
• Receipt of any other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study.
• History of severe reactions following immunization with influenza virus vaccines.
• Moderate to severe acute illness or febrile illness (oral temperature greater than 100*F) within 1 week prior to vaccination.
• Receipt of an experimental agent (vaccine, drug, biologic, device, blood product or medication) within 1 month prior to enrollment in this study, or expects to receive an experimental agent during study period.
• Known active human immunodeficiency virus, hepatitis B, or hepatitis C infection.
• History of alcohol or drug abuse in the last 5 years.
• History of Guillain-Barré Syndrome.
• Any acute or chronic medical condition that, in the opinion of the investigator, would render vaccination unsafe, interfere with the evaluation of responses, or render the subject unable to meet the requirements of the protocol. These conditions include, but are not limited to: history of significant renal impairment (dialysis and treatment for kidney disease, including diabetic and hypertensive kidney disease); subjects with diabetes mellitus, well-controlled with oral agents may enroll as long there has been no dosage increase within the past 6 months; insulin-dependent diabetes is excluded; cardiac insufficiency, if heart failure is present (New York Heart Association Functional Class III or IV); an arteriosclerotic event during the 6 months prior to enrollment (e.g., history of myocardial infarction, stroke, recanalization of femoral arteries, or transient ischemic attack).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FluBlok; Recombinant Trivalent Hemagglutinin Influenza Vaccine: 2005-2006 formulation containing 45μg of each hemagglutinin derived from A/New Caledonia (H1N1), A/Wisconsin (H3N2) and B/Ohio 135μg total	Biological: Influenza Vaccination; 0.5mL dose for intramuscular injection; Other Names: Fluzone; recombinant hemagglutinin; rHA; TIV; rHA0; FluBlok
Active Comparator: TIV (Fluzone); Licensed trivalent influenza vaccine (TIV): 2005-2006 formulation containing 15μg of each hemagglutinin derived from A/Wisconsin (H3N2), A/New Caledonia (H1N1) and B/Malaysia 45μg total (Fluzone, sanofi pasteur)	Biological: Influenza Vaccination; 0.5mL dose for intramuscular injection; Other Names: Fluzone; recombinant hemagglutinin; rHA; TIV; rHA0; FluBlok

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluation of safety and reactogenicity of FluBlok and TIV in medically stable adults 65 years and older.	influenza season

Secondary Outcome Measures

Outcome Measure	Time Frame
Comparison of relative efficacy and effectiveness of FluBlok and TIV in medically stable adults 65 years and older.	influenza season
Evaluation and comparison of immunogenicity of FluBlok and TIV in medically stable adults 65 years and older.	influenza season

Collaborators and Investigators

• Sponsor: Protein Sciences Corporation
• Investigators: Principal Investigator: Wendy A. Keitel, MD, Baylor College of Medicine; Principal Investigator: Hana M. El-Sahly, MD, Baylor College of Medicine; Principal Investigator: John J. Treanor, MD, University of Rochester Medical; Principal Investigator: Keith S. Reisinger, MD, Primary Physicians Research; Principal Investigator: Gregory A. Poland, MD, Mayo Clinic College of Medicine; Principal Investigator: Kenneth D. Lessans, MD, Passport Health Maryland; Principal Investigator: John J. Minneti, MD, Passport Health New Jersey; Principal Investigator: Kristen Lyke, MD, Center of Vaccine Development, University of Maryland

Publications and helpful links

General Publications

• Keitel WA, Treanor JJ, El Sahly HM, Gilbert A, Meyer AL, Patriarca PA, Cox MM. Comparative immunogenicity of recombinant influenza hemagglutinin (rHA) and trivalent inactivated vaccine (TIV) among persons > or =65 years old. Vaccine. 2009 Dec 11;28(2):379-85. doi: 10.1016/j.vaccine.2009.10.037. Epub 2009 Oct 29.
• Rajendran M, Nachbagauer R, Ermler ME, Bunduc P, Amanat F, Izikson R, Cox M, Palese P, Eichelberger M, Krammer F. Analysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin. mBio. 2017 Mar 21;8(2):e02281-16. doi: 10.1128/mBio.02281-16.
• Nachbagauer R, Choi A, Izikson R, Cox MM, Palese P, Krammer F. Age Dependence and Isotype Specificity of Influenza Virus Hemagglutinin Stalk-Reactive Antibodies in Humans. mBio. 2016 Jan 19;7(1):e01996-15. doi: 10.1128/mBio.01996-15.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): May 1, 2007
• Study Completion (Actual): May 1, 2007

Study Registration Dates

• First Submitted: October 30, 2006
• First Submitted That Met QC Criteria: November 1, 2006
• First Posted (Estimate): November 2, 2006

Study Record Updates

• Last Update Posted (Estimate): December 17, 2009
• Last Update Submitted That Met QC Criteria: December 16, 2009
• Last Verified: December 1, 2009

More Information

Terms related to this study

• Keywords: Influenza
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Agglutinins; Hemagglutinins
• Other Study ID Numbers: PSC03