Safety and Reactogenicity of FluBlok and Comparison of Immunogenicity, Efficacy and Effectiveness Against TIV

Evaluation of Safety and Reactogenicity of FluBlok, Trivalent Recombinant Influenza Vaccine, and Comparison of the Immunogenicity, Efficacy and Effectiveness of FluBlok to a Licensed Egg-Grown Influenza Vaccine in Adults Aged 50 to 64

The purpose of this study was to evaluate and compare the safety, reactogenicity, immunogenicity, relative efficacy and effectiveness of FluBlok to a licensed trivalent influenza vaccine (TIV)in healthy adults age 50-64 years.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: FluBlok Influenza Vaccination; Biological: TIV (Fluzone) 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): 602
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Fresno, California, United States, 93726
      • Kaiser Permanente Pediatric Clinic - Fresno
    • Hayward, California, United States, 94545
      • Kaiser Permanente Pediatric Clinic - Hayward
    • Roseville, California, United States, 95661
      • Kaiser Permanente Pediatric Clinic - Roseville
    • Sacramento, California, United States, 95823
      • Kaiser Permanente Pediatric Clinic - Sacramento
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • Kaiser Permanente

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults aged 50 to 64.
• Females should be at least 2 years post-menopausal or sterile or practicing accepted form of birth control (including: condom with spermicidal, licensed hormonal contraceptive, abstinence, IUD or monogamous relationship with a vasectomized partner).
• Healthy, as determined by oral temperature <100.0°F, medical history, and medical assessment w/ brief physical evaluation by RN (if indicated) 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 other than localized prostate cancer, diagnosed or treated actively during the past 5 years. Exceptions: Subjects with a history of lymphoproliferative disorder at any time in their life will be excluded, while subjects with a history of localized nonmelanotic skin cancer that has been completely removed during the past 5 years may be eligible.
• Long-term use of oral steroids, parenteral steroids, or high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (Nasal and topical steroids are allowed).
• Diagnosis of or treatment for bipolar disorder, severe major depression, schizophrenia or other major psychotic disorder in the past 3 months that is associated with severely impaired judgment or cognition.
• 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.
• Use of experimental vaccines or any influenza vaccine other than FluBlOk after May 31st 2007 for the 2008 Southern Hemisphere or 2007 to 2008 Northern hemisphere epidemic seasons.
• History of severe reactions following immunization with influenza virus vaccines.
• Moderate to severe acute illness or febrile illness (oral temperature greater than 100degreesF) 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.
• Subject is not available for three (3) or more consecutive weeks during active influenza season.
• 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: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FluBlok; Recombinant Trivalent Hemagglutinin Influenza Vaccine: 2007-2008 formulation containing 45μg of each hemagglutinin derived from A/Solomon Islands/03/2006 (H1N1), A/Wisconsin/67/2005 (H3N2), and B/Malaysia/2506/2004 135μg total	Biological: FluBlok Influenza Vaccination; 0.5mL dose for intramuscular injection; Other Names: recombinant hemagglutinin; rHA; rHA0; FluBlok
Active Comparator: TIV (Fluzone); Licensed Trivalent Influenza Vaccine (TIV): 2007-2008 formulation containing 15μg of each hemagglutinin derived from A/Solomon Islands/03/2006 (H1N1), A/Wisconsin/67/2005 (H3N2), and B/Malaysia/2506/2004 45μg total (Fluzone, sanofi pasteur)	Biological: TIV (Fluzone) Influenza Vaccination; 0.5mL dose for intramuscular injection; Other Names: Fluzone; TIV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Reactogenicity (Solicited) Adverse Events (AEs)	Solicited reactogenicity events included injection site pain, bruising, erythema and swelling. Solicited systemic AEs included fatigue, chills, arthralgias, myalgias, headache and nausea.	Reactogenicity days 0-7 following immunization; other AEs days 0-28 following immunization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation and Comparison of Immunogenicity of FluBlok and TIV in Healthy Adults 50-64 Years of Age.	Immunogenicity was assessed by measuring the difference in values in Hemagglutination-Inhibition Assay (HAI) titers in participants from Day 0 to Day 28, using Geometric Mean Titers (GMTs). The GMTs from the FluBlok and TIV groups were then compared.	Day 0 and Day 28
Percentage of Participants With Seroconversion	Percentage of participants with greater than or equal to a 4-fold rise in Hemagglutination-Inhibition Assay (HAI) titer over Day 0 at Day 28 following immunization	Day 28 following immunization at Day 0
Percentage of Participants With Seroprotection	Percentage of participants with (HAI titer greater than or equal to 40) at Day 28	Day 28 following immunization at Day 0

Collaborators and Investigators

• Sponsor: Protein Sciences Corporation
• Investigators: Principal Investigator: Roger Baxter, MD, Kaiser Permanenter Center for Vaccine Development

Publications and helpful links

General Publications

• Baxter R, Patriarca PA, Ensor K, Izikson R, Goldenthal KL, Cox MM. Evaluation of the safety, reactogenicity and immunogenicity of FluBlok(R) trivalent recombinant baculovirus-expressed hemagglutinin influenza vaccine administered intramuscularly to healthy adults 50-64 years of age. Vaccine. 2011 Mar 9;29(12):2272-8. doi: 10.1016/j.vaccine.2011.01.039. Epub 2011 Jan 28.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: October 4, 2007
• First Submitted That Met QC Criteria: October 4, 2007
• First Posted (Estimate): October 5, 2007

Study Record Updates

• Last Update Posted (Estimate): July 27, 2011
• Last Update Submitted That Met QC Criteria: July 25, 2011
• Last Verified: July 1, 2011

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: PSC06