Immunogenicity, Safety, Reactogenicity, Efficacy, Effectiveness and Lot Consistency of FluBlok

Study Overview
=================
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.

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

Conditions
-----------------
Influenza

Intervention / Treatment
-----------------
* Biological: FluBlok®
* Biological: Placebo


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FluBlok (Lots A, B, C)<br>Participants received a single 0.5 milliliters (mL) dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. | Biological: FluBlok®<br>* Dose: 0.5 mL, single dose; Route of administration: intramuscular. Recombinant Trivalent Hemagglutinin Influenza Vaccine containing 45 microgram (mcg) of each hemagglutinin derived from A/Solomon Islands/3/2006 (H1N1), A/Wisconsin/67/2005 (H3N2), and B/Malaysia/2506/2004<br>* Other names: rHA Trivalent Recombinant Hemagglutinin Influenza Vaccine;|
| Placebo Comparator: Placebo<br>Participants received a single dose of placebo matched to FluBlok, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. | Biological: Placebo<br>* Dose: 0.5 mL normal saline for injection, single dose; Route of administration: intramuscular<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Solicited Injection Site (Local) Reactions | Solicited reaction (reactogenicity event) was an adverse event (AE) that was pre-listed in electronic case report form(eCRF), considered to be related to vaccination and recorded by participant by means of memory aid. Injection sites reaction included pain,bruising,redness,swelling. Pain and bruising:Grade0: didn't have it at all; Grade1: noticed it, but it didn't interfere with usual activities at all; Grade2: had it, and it was bad enough to prevent a significant part of usual activities; Grade3: had it, and it prevented most or all of normal activities, or had to see a doctor for prescription medicine, Redness and swelling: participants measured largest diameter of any injection site reaction and grade them from 0 to 3, where Grade0: measured less than(<)10 milliliters(mm); Grade1: larger than or equal to(>=) 10mm and <20mm; Grade 2: >=20mm and <50mm; Grade3: >=50mm. Participants with multiple symptoms in same category were counted once per category using symptom with maximum grade | Within 7 days post vaccination | 
| Number of Participants Reporting Solicited Systemic Reactions | Solicited reaction (reactogenicity event) was an AE that was pre-listed in eCRF, considered to be related to vaccination recorded by the participant by means of a memory aid between the day of vaccination (Day 0) and Day 7 post vaccination. Systemic events included fever, fatigue, shivering, joint pain, muscle pain, headache, and nausea. Fever: >=100.4 degree Fahrenheit (ºF) to <101.1ºF; >=101.2ºF to <102.2ºF; >=102.2ºF; Fatigue, shivering, joint pain, muscle pain, headache and nausea: Grade 0: didn't have it at all; Grade 1: noticed it, but it didn't interfere with usual activities at all; Grade 2: had it, and it was bad enough to prevent a significant part of usual activities; and Grade 3: had it, and it prevented most or all of normal activities, or had to see a doctor for prescription medicine. Participants with multiple symptoms in the same category were counted once per category using the symptom with the maximum grade. | Within 7 days post vaccination | 
| Number of Participants Reporting Unsolicited Adverse Events | An AE was defined as any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a study vaccine, whether or not considered to be related to the study vaccine. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination, ascertained during follow-up visit or telephone contact up to (and including) the Day 28 contact, whether reported spontaneously by the participant or in response to general questions about current or interim health status. | From Day 0 (post-vaccination) through Day 28 post vaccination | 
| Lot Consistency: Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies Following FluBlok Vaccination | GMTs of anti-influenza antibodies were measured using a single radial immunodiffusion (SRID) assay for 3 strains: A/Solomon Islands [H1N1], A/Wisconsin [H3N2], and B/Malaysia. Titers were expressed in terms of 1/dilution. | Day 28 post vaccination | 
| Percentage of Participants With Positive Cell Culture/Culture-Confirmed Influenza Like Illness as Defined by Centers for Disease Control and Prevention (CDC-ILI) | CDC-defined ILI was defined as fever (body temperature >=100ºF oral accompanied by cough and/or sore throat, on the same day or on consecutive days) due to strains represented in the vaccine. | 14 days post vaccination through and up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Seroprotection to Influenza Vaccine Antigens After Vaccination With FluBlok | Anti-influenza antibodies were measured using an HAI assay for 3 strains: A/Solomon Islands [H1N1], A/Wisconsin [H3N2] and B/Malaysia. Seroprotection was defined as a post-vaccination HAI antibody titer of >=1:40. | 28 days post vaccination | 
| Percentage of Participants With Seroconversion to Influenza Vaccine Antigens After Vaccination With FluBlok | Anti-influenza antibodies were measured using an HAI assay for 3 strains: A/Solomon Islands [H1N1], A/Wisconsin [H3N2] and B/Malaysia. Seroconversion was defined as a post-vaccination titer of >=1:40 in participants with undetectable baseline antibody (HI titer = <1:10) or a >=4-fold rise in antibody in participants with a baseline titer of >=1:10, with the achievement of post-vaccination titer of at least 1:40. | 28 days post vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Influenza