Clinical trial NCT00328107: Immunogenicity and Safety of Trivalent Recombinant Hemagglutinin Influenza Vaccine in Healthy Adults
Official title: Evaluation of the Immunogenicity and Safety of Two Preparations of Trivalent Recombinant Baculovirus-Expressed Hemagglutinin Influenza Vaccine Administered Intramuscularly in Healthy Adults Ages 18-49 Years.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Influenza
Keywords: Influenza
Lead sponsor: Protein Sciences Corporation
Sponsor class: INDUSTRY
First posted: 2006-05-19
Enrollment: 459
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study was to determine the dose-related safety, immunogenicity, and protective efficacy of a trivalent recombinant hemagglutinin influenza vaccine in healthy adults.

Detailed description: All currently licensed influenza vaccines in the United States are produced in embryonated hen's eggs. There are several well-recognized disadvantages to the use of eggs as the substrate for influenza vaccine. Eggs require specialized manufacturing facilities and could be difficult to scale up rapidly in response to an emerging need such as a pandemic. It is usually necessary to adapt candidate vaccine viruses for high-yield growth in eggs, a process that can be time consuming, is not always successful, and can select receptor variants that may have suboptimal immunogenicity. In addition, agricultural diseases that affect 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 has been identified as a high-priority objective.

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

Eligibility criteria: Inclusion Criteria:

* Medically stable adults, 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 had a negative urine pregnancy test at the time of randomization and were willing to use an adequate form of contraception during the course of the study.

Exclusion Criteria:

* Any history of immunodeficiency or treatment with immunosuppressive medications. (Use of inhaled steroids or of topical steroids was not considered immunosuppressive; receipt of systemic glucocorticosteroids was not allowed if daily intake was \>10 mg of prednisone or equivalent).
* Presence of high-risk conditions or other characteristics considered to be indications for influenza vaccination, as defined by the Advisory Committee on Immunization Practices (ACIP).
* Acute febrile illness (defined as having a temperature ≥100degreesF) or upper respiratory tract illness within 72 hours of vaccination.
* Use of experimental vaccines or any influenza vaccine after May 31st 2004 for the 2005 Southern Hemisphere or 2004 to 2005 Northern hemisphere epidemic seasons.
* Use of any experimental medication within 30 days prior to study vaccination
* Women who were pregnant or breast-feeding.
* Subjects with a history of Guillain-Barré syndrome.
* Receipt of parenteral immunoglobulin within 30 days prior to study vaccination.
* Any acute or chronic condition that, in the opinion of the investigator, would render vaccination unsafe or interfere with the evaluation of response.

Primary outcomes:
measure: Evaluation of safety and reactogenicity of trivalent recombinant hemagglutinin influenza vaccine in healthy adults aged 18-49 years
timeFrame: influenza season
Secondary outcomes:
measure: Evaluation of the protective efficacy of a trivalent recombinant hemagglutinin influenza vaccine at two different formulations in healthy adults aged 18-49 years
timeFrame: influenza season
measure: Evaluation of the immunogenicity of the H1 and B components when formulated at either 15μg or 45μg per component in healthy adults aged 18-49 years
timeFrame: 28 days
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Rochester Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
affiliation: University of Rochester
name: John Treanor, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Treanor JJ, Schiff GM, Hayden FG, Brady RC, Hay CM, Meyer AL, Holden-Wiltse J, Liang H, Gilbert A, Cox M. Safety and immunogenicity of a baculovirus-expressed hemagglutinin influenza vaccine: a randomized controlled trial. JAMA. 2007 Apr 11;297(14):1577-82. doi: 10.1001/jama.297.14.1577.