A Study of the Efficacy, Safety and Tolerability Profile of CSL Limited's Influenza Virus Vaccine (CSL's IVV) Administered Intramuscularly in Healthy Adults

Study Overview
=================
Brief Summary
-----------------
This study will assess the Efficacy, Safety and Tolerability profile of CSL's Influenza Vaccine administered intramuscularly against laboratory-confirmed influenza illness in a population defined as being not at risk of severe complications following influenza infection.

Official Title
-----------------
A Phase IV, Randomized, Observer-Blind, Placebo-Controlled, Multi-Centre Study to Evaluate the Efficacy, Safety and Tolerability of CSL Limited's Influenza Virus Vaccine in Adults Aged ≥ 18 to < 65 Years.

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

Intervention / Treatment
-----------------
* Biological: CSL Limited Influenza Vaccine
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy males and females aged ≥ 18 to < 65 years at the time of vaccination Non pregnant/ non lactating females Exclusion Criteria: Hypersensitivity to influenza vaccine or allergy to any components of the Study Vaccines Vaccination against influenza in the previous 6 months Acute clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality Known history of Guillain-Barré Syndrome; Clinical signs of active infection and/or an oral temperature of ≥ 37.8 oC. History of neurological disorders or seizures Confirmed or suspected immunosuppressive condition or a previously diagnosed immunodeficiency disorder Current or recent immunosuppressive or immunomodulative therapy, including systemic corticosteroids Administration of immunoglobulins and/or any blood products; Participation in a clinical trial or use of an investigational compound; Vaccination with a registered vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior; Participants indicated to receive an influenza vaccine on an annual basis according to the local public health recommendations.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 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: 1<br> | Biological: CSL Limited Influenza Vaccine<br>* A single 0.5 mL, intramuscular Injection in the deltoid region of the arm on day 0.<br>|
| Other: 2<br> | Biological: Placebo<br>* Placebo<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CSL's IVV Overall Vaccine Efficacy (VE) Versus Placebo Through Assessment of Incidence of Laboratory Confirmed Influenza A/B Infection | Incidence of Laboratory Confirmed Influenza A/B infection was assessed per the study population in the 2008 and 2009 Southern Hemisphere influenza seasons. Vaccine efficacy = 100 x (1 - ratio of incidence rate). Ratio of incidence rate = active Study Vaccine recipient infection rate / placebo recipient infection rate. | 2008 and 2009 Southern Hemisphere influenza seasons, until 30 November 2009 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CSL's IVV Vaccine Efficacy Versus Placebo Through Assessment of Incidence of Laboratory Confirmed Influenza A/B Infection Due to Strains Matched to Vaccine Strains | Incidence of laboratory confirmed influenza A/B infection due to strains matched to vaccine strains was assessed per the study population in the 2008 and 2009 Southern Hemisphere influenza seasons. Vaccine efficacy = 100 x (1 - ratio of incidence rate). Ratio of incidence rate = active Study Vaccine recipient infection rate / Placebo recipient infection rate. | 2008 and 2009 Southern Hemisphere influenza seasons, until 30 November 2009 | 
| Incidence of Influenza-like Illness (ILI) | The criteria for the protocol defined ILI were as follows: At least one respiratory symptom: cough, sore throat or nasal congestion And at least one systemic symptom: fever (as defined by oral temperature ≥ 37.8°C (100.0°F), or feverishness (as defined by participant's subjective feeling of fever), chills or body aches. The CDC ILI case definition was the occurrence of fever (100°F [37.8°C] or higher) in conjunction with either cough or sore throat. | 2008 and 2009 Southern Hemisphere influenza seasons, until 30 November 2009 | 
| Percentage of Participants With a Minimum Post-vaccination Hemagglutination Inhibition (HI) Titer of 1:40, Year 2008 |  | 21 days after study vaccination | 
| Percentage of Participants With a Minimum Post-vaccination Hemagglutination Inhibition (HI) Titer of 1:40, Year 2009 |  | 21 days after study vaccination | 
| Percentage of Participants With Seroconversion 21 Days After Study Vaccination, Year 2008 | Seroconversion rate: defined as the percentage of participants with either a pre-vaccination HI titer < 1:10 and a post-vaccination HI titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and a minimum four-fold rise in post-vaccination HI antibody titer. | 21 days after study vaccination | 
| Percentage of Participants With Seroconversion 21 Days After Study Vaccination, Year 2009 | Seroconversion rate: defined as the percentage of participants with either a pre-vaccination HI titer < 1:10 and a post-vaccination HI titer ≥ 1:40 or a pre-vaccination titer ≥ 1:10 and a minimum four-fold rise in post-vaccination HI antibody titer. | 21 days after study vaccination | 
| Geometric Mean Fold Increase in HI Titer 21 Days After Study Vaccination, Year 2008 | Geometric mean fold increase in HI titer was defined as the geometric mean titer (GMT) after vaccination divided by the GMT before vaccination. | 21 days after study vaccination | 
| Geometric Mean Fold Increase in HI Titer Rate 21 Days After Study Vaccination, Year 2009 | Geometric mean fold increase in HI titer was defined as the geometric mean titer (GMT) after vaccination divided by the GMT before vaccination. | 21 days after study vaccination | 
| Frequency and Intensity of Local and Systemic Solicited Symptoms | Adverse event grading: Grade 1 (mild): Symptoms were easily tolerated and did not interfere with daily activities. Grade 2 (moderate): Discomfort was enough to cause some interference with daily activities. Grade 3 (severe): Symptoms that prevented normal, everyday activities. Fever Grade 1: ≥ 37.7°C - < 38.0°C (≥ 99.9 - < 100.4°F) Grade 2: ≥ 38.0°C - < 39.0°C (≥ 100.4 - < 102.2°F) Grade 3: ≥ 39.0°C (> 102.2°F) | 5 days after study vaccination | 
| Frequency and Intensity of Unsolicited Adverse Events (UAEs) | UAE grading: Grade 1 (mild): Symptoms were easily tolerated and did not interfere with daily activities. Grade 2 (moderate): Discomfort was enough to cause some interference with daily activities. Grade 3 (severe): Symptoms that prevented normal, everyday activities. | 21 days after study vaccination | 
| Serious Adverse Events (SAEs) | An SAE was any untoward medical occurrence that at any dose: Resulted in death; Was life-threatening; Required an unexpected in-participant hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability / incapacity; Was a congenital anomaly / birth defect; and / or Was medically significant (defined as an event that did not necessarily meet any of the SAE criteria, but was judged by the treating physician to potentially jeopardize the participant or require medical intervention to prevent one of the out | 180 days after study vaccination | 
| New Onsets of Chronic Illness (NOCI) | An NOCI was defined as the diagnosis of a chronic medical condition where the symptoms commenced or worsened following exposure to study vaccine and may have included those potentially controllable by medication (e.g., glaucoma, hypertension). | 180 days after study vaccination |