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

A Phase II, Single-centre, Randomised, Observer-blind Study to Evaluate the Immunogenicity, Safety and Tolerability of CSL's Monovalent H1N1 Influenza Virus Vaccine in Healthy Adults Aged 18 to < 65 Years.

The purpose of the study is to determine whether CSL425 is a safe and effective vaccine for eliciting an immune response to H1N1 influenza in healthy adults.

Study Overview

• Status: Completed
• Conditions: Influenza Caused by the Novel Influenza A (H1N1) Virus
• Intervention / Treatment: Biological: CSL425

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female aged >= 18 to < 65 years at the time of providing informed consent.

Exclusion Criteria:

• Known hypersensitivity to a previous dose of influenza virus vaccine or allergy to eggs, chicken protein, thiomersal, neomycin, polymyxin, or any components of the Study Vaccine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CSL425 (15 mcg); 15 mcg of haemagglutinin antigen per dose. 0.25 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	Biological: CSL425; CSL's 2009 H1N1 Influenza Vaccine, thimerosal 0.01% (weight/volume)
Experimental: CSL425 (30 mcg); 30 mcg of haemagglutinin antigen per dose. 0.5 mL intramuscular injection into the deltoid region of the arm on Day 0 and Day 21	Biological: CSL425; CSL's 2009 H1N1 Influenza Vaccine, thimerosal 0.01% (weight/volume)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemagglutination Inhibition (HI) and Microneutralisation (MN) Antibody Titre Seroconversion Rate After the First Vaccination	Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination antibody titre of 1:40 or more; or participants with a pre-vaccination titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre.	Before and 21 days after the first vaccination
HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination	Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination antibody titre of 1:40 or more; or participants with a pre-vaccination titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre.	Before and 21 days after the second vaccination
Geometric Mean Fold Increase (GMFI) in the HI and MN Antibody Titre After the First Vaccination	GMFI in antibody titre was defined as the geometric mean of the fold increase in the post-vaccination antibody titre over the pre-vaccination antibody titre.	Before and 21 days after the first vaccination
GMFI in the HI and MN Antibody Titer After the Second Vaccination	GMFI in antibody titre was defined as the geometric mean of the fold increase in the post-vaccination antibody titre over the pre-vaccination antibody titre.	Before and 21 days after the second vaccination
Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination		21 days after the first vaccination
Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination		21 days after the second vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HI and MN Antibody Titre Seroconversion Rate After the First Vaccination by Age Group	Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination antibody titre of 1:40 or more; or participants with a pre-vaccination titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre. Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.	Before and 21 days after the first vaccination
HI and MN Antibody Titre Seroconversion Rate After the Second Vaccination by Age Group	Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination antibody titre of 1:40 or more; or participants with a pre-vaccination titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre. Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.	Before and 21 days after the second vaccination
GMFI in the HI and MN Antibody Titre After the First Vaccination by Age Group	GMFI in antibody titre was defined as the geometric mean of the fold increase in the post-vaccination antibody titre over the pre-vaccination antibody titre. Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.	Before and 21 days after the first vaccination
GMFI in the HI and MN Antibody Titre After the Second Vaccination by Age Group	GMFI in antibody titre was defined as the geometric mean of the fold increase in the post-vaccination antibody titre over the pre-vaccination antibody titre. Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.	Before and 21 days after the second vaccination
Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the First Vaccination by Age Group	Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.	21 days after the first vaccination
Percentage of Participants Achieving a HI or MN Antibody Titre of 1:40 or More After the Second Vaccination by Age Group	Adults were aged from 18 to 49 years; Older adults were aged from 50 to 64 years.	21 days after the second vaccination
Percentage of Participants With a Baseline Titre Less Than 1:10 Achieving Seroconversion After Vaccination	The number of participants with a baseline titre less than 1:10 differed according to antibody assay (HI or MN) and is shown in the category titles accordingly. The total number of participants analysed includes all evaluable participants; however, the analysis is stratified by baseline titre and those participants with a baseline titre less than 1:10 are presented in this outcome measure while those with a baseline titre of 1:10 or more are presented in a separate outcome measure. Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination titre of 1:40 or more; or participants with a pre-vaccination titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre.	Before and 21 days after each vaccination
Percentage of Participants With a Baseline Titre Greater Than or Equal to 1:10 Achieving Seroconversion After Vaccination	The number of participants with a baseline titre greater than or equal to 1:10 differed according to antibody assay (HI or MN) and is shown in the category titles accordingly. The total number of participants analysed includes all evaluable participants; however, the analysis is stratified by baseline titre and those participants with a baseline titre of 1:10 or more are presented in this outcome measure while those with a baseline titre less than 1:10 are presented in a separate outcome measure. Antibody titre seroconversion was defined as participants with a pre-vaccination titre of less than 1:10 achieving a post-vaccination titre of 1:40 or more; or participants with a pre-vaccination titre of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titre (ie, a significant increase in antibody titre after vaccination).	Before and 21 days after each vaccination
GMFI in the HI Antibody Titre 180 Days After the Second Vaccination	The GMFI in antibody titre was calculated by taking the anti-logs of the means of the log transformed fold-increases in the antibody titre 180 days after the second vaccination over the antibody titre 21 days after the second vaccination.	21 days and 180 days after the second vaccination
Percentage of Participants Achieving a HI Antibody Titre of 1:40 or More 180 Days After the Second Vaccination		180 days after the second vaccination
Frequency and Intensity of Solicited Local Adverse Events (AEs) After the First Vaccination	Solicited AEs included AEs that were specifically sought for. Grade 3 solicited AE definitions: Prevented normal daily activities; Size > 100 mm for injection site redness, induration/swelling, and bruising.	From Day 0 to Day 6 after the first vaccination
Duration of Solicited Local AEs After the First Vaccination	Solicited AEs included AEs that were specifically sought for.	From Day 0 to Day 6 after the first vaccination and up to Day 20 after the first vaccination if AE is ongoing at Day 7
Frequency and Intensity of Solicited Local AEs After the Second Vaccination	Solicited AEs included AEs that were specifically sought for. Grade 3 solicited AE definitions: Prevented normal daily activities; Size > 100 mm for injection site redness, induration/swelling, and bruising.	From Day 0 to Day 6 after the second vaccination
Duration of Solicited Local AEs After the Second Vaccination	Solicited AEs included AEs that were specifically sought for.	From Day 0 to Day 6 after the second vaccination and up to Day 20 after the second vaccination if AE is ongoing at Day 7
Frequency and Intensity of Solicited Systemic AEs After the First Vaccination	Solicited AEs included AEs that were specifically sought for. Grade 3 solicited AE definitions: Prevented normal daily activities; Temperature 102.2°F (39.0°C) or more for fevers.	From Day 0 to Day 6 after the first vaccination
Duration of Solicited Systemic AEs After the First Vaccination	Solicited AEs included AEs that were specifically sought for.	From Day 0 to Day 6 after the first vaccination and up to Day 20 after the first vaccination if AE is ongoing at Day 7
Frequency and Intensity of Solicited Systemic AEs After the Second Vaccination	Solicited AEs included AEs that were specifically sought for. Grade 3 solicited AE definitions: Prevented normal daily activities; Temperature 102.2°F (39.0°C) or more for fevers.	From Day 0 to Day 6 after the second vaccination
Duration of Solicited Systemic AEs After the Second Vaccination	Solicited AEs included AEs that were specifically sought for.	From Day 0 to Day 6 after the second vaccination and up to Day 20 after the second vaccination if AE is ongoing at Day 7
Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs), and New Onset of Chronic Illnesses (NOCIs)	An AESI was defined as an AE for which the association with seasonal influenza vaccine was unclear. 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 AEs	Unsolicited AEs included AEs other than those specifically sought for. The grading definitions were: Mild (Grade 1): Symptoms were easily tolerated and did not interfere with daily activities. Moderate (Grade 2): Enough discomfort to cause some interference with daily activities. Severe (Grade 3): Incapacitating, with inability to work or do usual activities.	From Day 0 to Day 20 after vaccination; up to 180 days after the last vaccination for SAEs, AESIs, and NOCIs

Collaborators and Investigators

• Sponsor: Seqirus
• Investigators: Study Director: Director, Vaccines Clinical Development, Seqirus

Publications and helpful links

General Publications

• Greenberg ME, Lai MH, Hartel GF, Wichems CH, Gittleson C, Bennet J, Dawson G, Hu W, Leggio C, Washington D, Basser RL. Response to a monovalent 2009 influenza A (H1N1) vaccine. N Engl J Med. 2009 Dec 17;361(25):2405-13. doi: 10.1056/NEJMoa0907413. Epub 2009 Sep 10.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: July 13, 2009
• First Submitted That Met QC Criteria: July 13, 2009
• First Posted (Estimate): July 14, 2009

Study Record Updates

• Last Update Posted (Actual): June 28, 2018
• Last Update Submitted That Met QC Criteria: April 25, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: CSLCT-CAL-09-59

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No