Clinical trial NCT00539981: Immunogenicity, Safety, Reactogenicity, Efficacy, Effectiveness and Lot Consistency of FluBlok
Official title: Evaluation of the Immunogenicity, Safety, Reactogenicity, Efficacy, Effectiveness and Lot Consistency of FluBlok® Trivalent Recombinant Baculovirus-Expressed Hemagglutinin Influenza Vaccine in Healthy Adults Aged 18 to 49 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza
Keywords: Influenza
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Protein Sciences Corporation
First posted: 2007-10-05
Enrollment: 4648
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
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 a single dose of FluBlok in terms of safety, efficacy and effectiveness in prevention of influenza and influenza-like illness and assess clinical lot-to-lot consistency in manufacturing by evaluating and comparing the immunogenicity of three different lots of FluBlok in a subset of participants.

Detailed description: All currently licensed influenza vaccines in the United States were produced in embryonated hen's eggs. There were several well-recognized disadvantages to the use of eggs as the substrate for influenza vaccine. Eggs required specialized manufacturing facilities and could be difficult to scale up rapidly in response to an emerging need such as a pandemic. It was usually necessary to adapt candidate vaccine viruses for high-yield growth in eggs, a process that could be time consuming, was not always successful, and could select receptor variants that might have suboptimal immunogenicity. In addition, agricultural diseases that affected chicken flocks, and that might be an important issue in a pandemic due to an avian influenza virus strain, could easily disrupt the supply of eggs for vaccine manufacturing. Therefore, development of alternative substrates for influenza vaccine production had been identified as a high-priority objective.

One potential alternative method for production of influenza vaccine was expression of the influenza virus hemagglutinin (HA) using recombinant deoxyribonucleic acid (DNA) techniques. This alternative avoided dependence on eggs and was very efficient because of the high levels of protein expression under the control of the baculovirus polyhedrin promoter.

Eligibility criteria: Inclusion Criteria:

* Healthy adult aged 18-49 years.
* Provided informed consent prior to any study procedures.
* Able to comply with all study procedures.
* Available for follow-up for the duration of the influenza season.
* Women of child-bearing potential must have had a negative urine pregnancy test at the time of randomization and must be willing to use an adequate form of contraception (includes abstinence, condom with spermicide, licensed hormonal contraceptive, intrauterine device \[IUD\], monogamous relationship with a vasectomized partner) during the course of the study.

Exclusion Criteria:

* Long-term use of oral steroids, parenteral steroids, or high-dose inhaled steroids (greater than \[\>\] 800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (Nasal and topical steroids were allowed).
* Presence of high-risk conditions or other characteristics were considered to be indication for influenza vaccination, as defined by the Advisory Committee on Immunization Practices.
* Acute febrile illness (defined as having a temperature greater than or equal to \[\>=\]100 degrees Fahrenheit) or upper respiratory tract illness within 72 hours of vaccination. Participants with acute febrile illness were rescheduled after fever resolved.
* 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.
* Immunosuppression as a result of an underlying illness or treatment, or used anticancer chemotherapy or radiation therapy within the preceding 36 months.
* Any malignancy diagnosed or treated actively during the past five (5) years, with two (2) exceptions. Participant with any history of lymphoproliferative disorder were excluded. However, participants with a history of localized non-melanotic skin cancer were eligible.
* Receipt of any other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study.
* Receipt of an experimental agent (vaccine, drug, biologic, device, blood product or medication) within 1 month prior to enrollment in this study, or expected to receive an experimental agent during study period.
* Receipt of parenteral immunoglobulin or other blood product within the three months prior to study vaccination.
* 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.
* Known active human immunodeficiency virus, hepatitis B, or hepatitis C infection.
* History of alcohol or drug abuse in the last 5 years.
* Not available for three or more consecutive weeks during flu surveillance period.
* Any acute or chronic condition that, in the opinion of the investigator, would render vaccination unsafe or interfere with the evaluation of responses or render the participant unable to meet the requirements of the protocol.

Primary outcomes:
measure: Number of Participants Reporting Solicited Injection Site (Local) Reactions
timeFrame: Within 7 days post vaccination
measure: Number of Participants Reporting Solicited Systemic Reactions
timeFrame: Within 7 days post vaccination
measure: Number of Participants Reporting Unsolicited Adverse Events
timeFrame: From Day 0 (post-vaccination) through Day 28 post vaccination
measure: Lot Consistency: Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies Following FluBlok Vaccination
timeFrame: Day 28 post vaccination
measure: Percentage of Participants With Positive Cell Culture/Culture-Confirmed Influenza Like Illness as Defined by Centers for Disease Control and Prevention (CDC-ILI)
timeFrame: 14 days post vaccination through and up to 6 months
Secondary outcomes:
measure: Percentage of Participants With Seroprotection to Influenza Vaccine Antigens After Vaccination With FluBlok
timeFrame: 28 days post vaccination
measure: Percentage of Participants With Seroconversion to Influenza Vaccine Antigens After Vaccination With FluBlok
timeFrame: 28 days post vaccination
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Impact Clinical Trials
state: California
city: Sacramento
country: United States
facility: Benchmark Research - Sacramento
state: California
city: San Francisco
country: United States
facility: Benchmark Research - San Francisco
state: California
city: Pembroke Pines
country: United States
facility: University Clinical Research, Inc
state: Florida
city: Overland Park
country: United States
facility: Vince and Associates
state: Kansas
city: Bardstown
country: United States
facility: Kentucky pediatric /Adult Research
state: Kentucky
city: Metairie
country: United States
facility: Benchmarch Research - New Orleans
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland - Baltimore
state: Maryland
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Omaha
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Endwell
country: United States
facility: Regional Clinical Research, Inc.
state: New York
city: Rochester
country: United States
facility: Rochester Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Carolina Medical Trials
state: North Carolina
city: Cincinnati
country: United States
facility: Sterling Research
state: Ohio
city: Pittsburgh
country: United States
facility: Primary Physicians Research - Pediatric Alliance St. Clair
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Primary Physicians Research
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Benchmarch Research - Austin
state: Texas
city: Fort Worth
country: United States
facility: Benchmark Research - Fort Worth
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Angelo
country: United States
facility: Benchmark Research - San Angelo
state: Texas
city: Salt Lake City
country: United States
facility: Jean Brown Research
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Marshfield
country: United States
facility: Marshfield Clinic
state: Wisconsin
Study officials:
affiliation: University of Rochester
name: John J Treanor, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Treanor JJ, El Sahly H, King J, Graham I, Izikson R, Kohberger R, Patriarca P, Cox M. Protective efficacy of a trivalent recombinant hemagglutinin protein vaccine (FluBlok(R)) against influenza in healthy adults: a randomized, placebo-controlled trial. Vaccine. 2011 Oct 13;29(44):7733-9. doi: 10.1016/j.vaccine.2011.07.128. Epub 2011 Aug 9.
citation: 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.
citation: 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.