Ross River Virus (RRV) Vaccine Study

A Phase 3 Study to Assess the Immunogenicity, Safety, and Consistency of Lot Manufacture of Ross River Virus (RRV) Vaccine in Healthy Male and Female Subjects 16 Years of Age and Older

The purpose of the study is to verify the safety and adequacy of the immune response produced by a 2.5 µg, adjuvanted (aluminium hydroxide) dose of Ross River Virus (RRV) vaccine and to demonstrate the consistency of manufacture of 3 separate lots of RRV vaccine.

Study Overview

• Status: Completed
• Conditions: Prophylaxis of Ross River Virus Infection
• Intervention / Treatment: Biological: Ross River Virus Vaccine

• Study Type: Interventional
• Enrollment (Actual): 1968
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Byron Bay, New South Wales, Australia, 2481
      • Holdsworth House
    • Darlinghurst, New South Wales, Australia, 2010
      • Holdsworth House Medical Practice
    • Darlinghurst, New South Wales, Australia, 2010
      • St. Vincents Hospital
    • Westmead, New South Wales, Australia, 2145
      • National Centre for Immunisation Research & Surveillance, The Children´s Hospital Westmead
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • AusTrials Pty Limited
    • Auchenflower, Queensland, Australia, 4066
      • Wesley Research Institute Clinical Trials Centre
    • Caboolture, Queensland, Australia, 4510
      • AusTrials Pty Limited
    • Cairns, Queensland, Australia, 4870
      • James Cook University
    • Herston, Queensland, Australia, 4029
      • QPID Clinical Trials Centre, Royal Children´s Hospital
    • Herston, Queensland, Australia, 4006
      • Q-Pharm Pty Limited
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Dept of Microbiology & Infectious Diseases
    • North Adelaide, South Australia, Australia, 5006
      • Melbourne Street
  • Victoria
    • Geelong, Victoria, Australia, 3220
      • Barwon Health - The Geelong Hospital, Dept Clinical & Biomedical Sciences
    • Heidelberg, Victoria, Australia, 3084
      • Centre for Clinical Studies
    • Malvern East, Victoria, Australia, 3145
      • Emeritus Research
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research
    • Perth, Western Australia, Australia, 6840
      • Princess Margaret Hospital for Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is 16 to 59 years of age on the day of screening (for Stratum A only)
• Subject is 60 years of age or older on the day of screening (for Stratum B only)
• Subject and, if applicable, subject's parent(s)/legal guardian(s) has (/have) an understanding of the study and its procedures, agree to its provisions, and give written informed consent prior to study entry
• Subject provides written assent according to his/her age, if applicable
• Subject is generally healthy as determined by the investigator's clinical judgment based upon medical history and physical examination
• Subject is physically and mentally capable of participating in the study and following study procedures
• Subject agrees to keep a daily record of symptoms for the duration of the study
• If female of childbearing potential - subject has a negative urine pregnancy test result within 24 hours of the scheduled first vaccination and agree to employ adequate birth control measures for the duration of the study

Exclusion Criteria:

• Subject has a Body Mass Index > 35.0
• Subject has an elevated blood pressure at screening of > 159 mmHg systolic and/or > 99 mmHg diastolic while seated and at rest and confirmed by 2 additional measurements taken at least 30 minutes apart (while seated and at rest)
• Subject has any inherited or acquired immune deficiency
• Subject has or has a recent history of significant neurological, cardiovascular, respiratory (including asthma), hepatic, metabolic, rheumatic, autoimmune, hematological or renal disorder
• Subject has a history of arthritis (including RRV disease, joint swelling, tenderness, warmth or erythema) on more than one occasion, not related to trauma (including running) or any episode of non-trauma related arthritis within the previous 6 months
• Subject has a disease or is currently undergoing a form of treatment or was undergoing a form of treatment within 30 days prior to study entry that could be expected to influence immune response. Such treatment includes, but is not limited to, systemic or high dose inhaled (> 800 μg/day of beclomethasone dipropionate or equivalent), corticosteroids, radiation treatment or other immunosuppressive or cytotoxic drugs
• Subjects has received any vaccination within 30 days prior to study entry
• Subject has received a blood transfusion or immunoglobulins within 90 days prior to study entry
• Subject has donated blood or plasma within 30 days prior to study entry
• Subject has a history of any vaccine related contraindicating event (eg, anaphylaxis, allergy to components of the test vaccine, other known contraindications)
• Subject has a dermatologic condition or tattoos which may interfere with injection site reaction rating
• Subject has participated in another clinical study involving an investigational drug, biological product or device within 30 days prior to enrollment in this study or is scheduled to participate in another clinical study involving an investigational drug, biological or device during the course of this study
• Subject has functional or surgical asplenia
• Subject has a known or suspected problem with alcohol or drug abuse
• Subject is a member of the team conducting this study or is in a dependent relationship with one of the study team members. Dependent relationships include close relatives (ie, children, partner/spouse, siblings, parents) as well as employees of the investigator or site personnel conducting this study
• Subject is pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ross River Virus Vaccine; Subjects will be randomized in equal numbers (1:1:1) to receive one of three different lots of the vaccine on Day 1, Day 22 and Day 181. (The study is blinded with regard to which vaccine lot is administered to a subject but all subjects will receive 3 injections with a 2.5 µg aluminum hydroxide adjuvanted dose of RRV vaccine.)	Biological: Ross River Virus Vaccine; Ross River Virus Vaccine (Formalin Treated, UV Inactivated, Vero Cell-Derived) with Aluminum Hydroxide Adjuvant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune response measured by Ross River Vaccine (RRV)-specific neutralizing titer 21 days after the 3rd vaccination as determined by RRV microneutralization (μNT) assay		21 days after 3rd vaccination
Rate of subjects with a RRV-specific neutralizing titer	Rate of subjects with a RRV-specific neutralizing titer 21 days after the third vaccination as determined by RRV microneutralization (μNT) assay	21 days after 3rd vaccination
Frequency and severity of injection site and systemic reactions within 7 days of any study vaccination		Within 7 days of any study vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of subjects with a RRV-specific neutralizing titer		21 days after 1st + 2nd vaccination and 180 days after 1st + 3rd vaccination
Rate of subjects with seroconversion	Seroconversion is defined as a positive RRV-specific neutralizing titer after vaccination (>= 1:10) when RRV-specific neutralizing titer at baseline is < 1.4 or a minimum 4-fold RRV-specific neutralizing titer increase as compared to baseline	21 days after 1st, 2nd + 3rd vaccination and 180 days after 1st + 3rd vaccination
Immune response measured by RRV-specific neutralizing titer		21 days after 1st + 2nd and 180 days after 1st + 3rd vaccination
Fold increase of RRV-specific neutralizing titer	Fold increase as compared to baseline	21 days after 1st, 2nd + 3rd vaccination and 180 days after 1st + 3rd vaccination
Rate of subjects with a RRV-specific immunoglobulin G (IgG) titer		21 days after 1st, 2nd + 3rd vaccination and 180 days after 1st + 3rd vaccination
Rate of subjects with seroconversion (defined as a positive RRV-specific IgG) titer after vaccination		21 days after 1st, 2nd + 3rd vaccination and 180 days after 1st + 3rd vaccination
Immune response measured by RRV-specific IgG titer		21 days after 1st, 2nd + 3rd vaccination and 180 days after 1st + 3rd vaccination
Fold increase of RRV-specific IgG titer	Fold increase as compared to baseline	21 days after 1st, 2nd + 3rd vaccination and 180 days after 1st + 3rd vaccination
Frequency and severity of any systemic reactions		Within first 21 days of study vaccination
Frequency and severity of any injection site reactions		Within first 21 days following a study vaccination
Frequency and severity of any adverse event		During entire study period
Rate of subjects experiencing arthritis associated with one or more of the systemic symptoms consistent with RRV disease	Arthritis is defined as soft tissue "synovitic"swelling, ie joint effusion or synovial tissue thickening, or both, with or without pain localized to the affected joint. Symptoms consistent with RRV disease include fever, fatigue, malaise, rash, arthralgia, myalgia, lymphadenopathy, splenomegaly, sore throat, diarrhea, paresthesia, headache, neck stiffness, and photophobia.	Occurring at least 3 days after vaccination and lasting for more than 3 weeks

Collaborators and Investigators

• Sponsor: Ology Bioservices
• Investigators: Study Director: Alexander Geisberger, MD, Baxter Innovations GmbH

Publications and helpful links

General Publications

• Wressnigg N, van der Velden MV, Portsmouth D, Draxler W, O'Rourke M, Richmond P, Hall S, McBride WJ, Redfern A, Aaskov J, Barrett PN, Aichinger G. An inactivated Ross River virus vaccine is well tolerated and immunogenic in an adult population in a randomized phase 3 trial. Clin Vaccine Immunol. 2015 Mar;22(3):267-73. doi: 10.1128/CVI.00546-14. Epub 2014 Dec 24.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: November 15, 2010
• First Submitted That Met QC Criteria: November 16, 2010
• First Posted (Estimate): November 17, 2010

Study Record Updates

• Last Update Posted (Estimate): October 9, 2015
• Last Update Submitted That Met QC Criteria: October 7, 2015
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Togaviridae Infections; Alphavirus Infections
• Other Study ID Numbers: 880801