Clinical trial NCT00539864: Safety and Reactogenicity of FluBlok and Comparison of Immunogenicity, Efficacy and Effectiveness Against TIV
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza
Keywords: Influenza
Lead sponsor: Protein Sciences Corporation
Sponsor class: INDUSTRY
First posted: 2007-10-05
Enrollment: 602
Sex: ALL
Minimum age (years): 50
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of Participants With Reactogenicity (Solicited) Adverse Events (AEs)
timeFrame: Reactogenicity days 0-7 following immunization; other AEs days 0-28 following immunization
Secondary outcomes:
measure: Evaluation and Comparison of Immunogenicity of FluBlok and TIV in Healthy Adults 50-64 Years of Age.
timeFrame: Day 0 and Day 28
measure: Percentage of Participants With Seroconversion
timeFrame: Day 28 following immunization at Day 0
measure: Percentage of Participants With Seroprotection
timeFrame: Day 28 following immunization at Day 0
Other outcomes:
Locations:
city: Fresno
country: United States
facility: Kaiser Permanente Pediatric Clinic - Fresno
state: California
city: Hayward
country: United States
facility: Kaiser Permanente Pediatric Clinic - Hayward
state: California
city: Roseville
country: United States
facility: Kaiser Permanente Pediatric Clinic - Roseville
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Pediatric Clinic - Sacramento
state: California
city: Honolulu
country: United States
facility: Kaiser Permanente
state: Hawaii
Study officials:
affiliation: Kaiser Permanenter Center for Vaccine Development
name: Roger Baxter, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.