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

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.

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.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Placebo; Biological: CSL Limited Influenza Vaccine

• Study Type: Interventional
• Enrollment (Actual): 7500
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Canberra, Australian Capital Territory, Australia
      • The Clinical Trials Unit, Canberra Hospital
  • New South Wales
    • Brookvale, New South Wales, Australia
      • Australian Clinical Research Organisation
    • Caringbah, New South Wales, Australia
      • Australian Clinical Research Organisation
    • Randwick, New South Wales, Australia
      • Eastern Area Health Service, Prince of Wales Hospital
    • Westmead, New South Wales, Australia
      • National Centre for Immunisation Research & Surveillance (NCIRS) The Children's Hospital at Westmead
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Australian Clinical Research Organisation
    • Brisbane, Queensland, Australia
      • Trialworks Clinical Research Services
    • Caboolture, Queensland, Australia, 4510
      • Australian Clinical Research Organisation Caboolture Clinical Research Centre
    • Cairns, Queensland, Australia
      • School of Medicine, James Cook University, Cairns Base Hospital
    • Gold Coast, Queensland, Australia
      • Gold Coast Hospital
    • Kippa Ring, Queensland, Australia
      • Australian Clinical Research Organisation
  • South Australia
    • Adelaide, South Australia, Australia
      • CMAX, a division of IDT Australia
    • Adelaide, South Australia, Australia
      • Paediatric Trials Unit, Women's and Children's Hospital
    • Royal Park, South Australia, Australia, 5014
      • Primary Old Port Road Medical and Dental Centre
  • Tasmania
    • Hobart, Tasmania, Australia
      • Sexual Health Service
  • Victoria
    • Geelong, Victoria, Australia
      • Barwon Health, Geelong Hospital
    • Malvern East, Victoria, Australia
      • Emeritus Research
    • Melbourne, Victoria, Australia
      • Murdoch Childrens Research Institute
  • Western Australia
    • Perth, Western Australia, Australia
      • Lung Institute of Western Australia
    • Perth, Western Australia, Australia
      • Princess Margaret Hospital for Children
• New Zealand
  • Auckland, New Zealand
    • Auckland Clinical Studies
  • Christchurch, New Zealand
    • Southern Clinical Trials
  • Christchurch, New Zealand
    • 198 Youth Health Centre
  • Dunedin, New Zealand
    • RMC Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 62 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Biological: CSL Limited Influenza Vaccine; A single 0.5 mL, intramuscular Injection in the deltoid region of the arm on day 0.
Other: 2	Biological: Placebo; Placebo

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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Mcbride WJH, Abhayaratna WP, Barr I, Booy R, Carapetis J, Carson S, De Looze F, Ellis-Pegler R, Heron L, Karrasch J, Marshall H, Mcvernon J, Nolan T, Rawlinson W, Reid J, Richmond P, Shakib S, Basser RL, Hartel GF, Lai MH, Rockman S, Greenberg ME. Efficacy of a trivalent influenza vaccine against seasonal strains and against 2009 pandemic H1N1: A randomized, placebo-controlled trial. Vaccine. 2016 Sep 22;34(41):4991-4997. doi: 10.1016/j.vaccine.2016.08.038. Epub 2016 Aug 29.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: November 20, 2007
• First Submitted That Met QC Criteria: November 21, 2007
• First Posted (Estimate): November 22, 2007

Study Record Updates

• Last Update Posted (Actual): November 21, 2017
• Last Update Submitted That Met QC Criteria: October 18, 2017
• Last Verified: October 1, 2017

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-USF-06-28