A Clinical Trial of CSL's 2009 H1N1 Influenza Vaccine (CSL425) in Healthy Adults in the USA

Study Overview
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Brief Summary
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The purpose of this study is to determine whether CSL425 is a safe and effective vaccine for eliciting an immune response to H1N1 influenza in healthy adults

Official Title
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A Phase II, Multicenter, Randomized, Observer-Blind, Placebo-Controlled Study to Evaluate the Immunogenicity, Safety and Tolerability of CSL's 2009 H1N1 Influenza Vaccine (CSL425) in Healthy Adults Aged 18 Years and Older

Conditions
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Influenza

Intervention / Treatment
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* Biological: CSL425
* Biological: CSL425
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18 and older, inclusive, at the time of providing informed consent. Females of child bearing potential (i.e., ovulating, pre-menopausal, not surgically sterile) must be abstinent or be willing to use a medically accepted contraceptive regimen for the duration of the study. Females of child bearing potential must return a negative urine pregnancy test result at enrolment and prior to each study vaccination. Exclusion Criteria: Known hypersensitivity to a previous dose of influenza virus vaccine or allergy to eggs, chicken protein, thimerosal, neomycin, polymyxin, or any components of the Study Vaccine.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CSL425 (7.5 mcg)<br>7.5 mcg of hemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21 | Biological: CSL425<br>* CSL's 2009 H1N1 Influenza Vaccine, thimerosal-free.<br>|
| Experimental: CSL425 (15 mcg)<br>15 mcg of hemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21. | Biological: CSL425<br>* CSL's 2009 H1N1 Influenza Vaccine, thimerosal 0.01% (weight/volume).<br>|
| Experimental: CSL425 (30 mcg)<br>30 mcg of hemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21 | Biological: CSL425<br>* CSL's 2009 H1N1 Influenza Vaccine, thimerosal 0.01% (weight/volume).<br>|
| Placebo Comparator: Placebo<br>Vaccine diluent. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21. | Biological: Placebo<br>* Vaccine diluent, thimerosal 0.01% (weight/volume).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion Rate 21 Days After the First Vaccination | Seroconversion rate: the proportion of participants achieving seroconversion in hemagglutination inhibition (HI) antibody titer. Seroconversion is defined as participants with a baseline titer of less than 1:10 achieving a post-vaccination HI antibody titer of 1:40 or more; or participants with a baseline HI titer of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titer. | 21 days after the first vaccination | 
| Seroconversion Rate 21 Days After the Second Vaccination | Seroconversion rate: the percentage of participants achieving seroconversion in HI antibody titer. Seroconversion is defined as participants with a pre-vaccination titer of less than 1:10 achieving a post-vaccination HI antibody titer of 1:40 or more; or participants with a pre-vaccination HI titer of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titer. | 21 days after the second vaccination | 
| Percentage of Participants Achieving an Hemagglutination Inhibition (HI) Antibody Titer of 1:40 or More 21 Days After the First Vaccination |  | 21 days after the first vaccination | 
| Percentage of Participants Achieving an HI Antibody Titer of 1:40 or More 21 Days After the Second Vaccination |  | 21 days after the second vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and Intensity of Solicited Adverse Events After the First Vaccination | Grade 3 solicited adverse event (AE) definitions: Prevented normal daily activities; Size > 100 mm for injection site redness or induration/swelling; Temperature 102.2°F (39.0°C) or more for fevers. | During the 7 days after the first vaccination | 
| Duration of Solicited Local Adverse Events After the First Vaccination |  | During the 7 days after the first vaccination, and day 7 - day 21 for ongoing AEs | 
| Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESI) and New Onset of Chronic Illness (NOCI) | A NOCI was defined as the diagnosis of a new medical condition that was chronic in nature, including those potentially controllable by medication (eg, diabetes, asthma). | Up to 180 days after the last vaccination | 
| Frequency and Intensity of Unsolicited Adverse Events (UAE) After the First or Second Vaccination | Unsolicited adverse event (UAE) grading: Grade 1 (mild): Symptoms were easily tolerated and did not interfere with daily activities. Grade 2 (moderate): Enough discomfort to cause some interference with daily activities. Grade 3 (severe): Symptoms that prevented normal, everyday activities. | Day 0 to Day 20 after each vaccination; up to Day 180 after the last vaccination for SAEs, AESI and NOCI |