Clinical trial NCT01242670: Ross River Virus (RRV) Vaccine Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prophylaxis of Ross River Virus Infection
Lead sponsor: Resilience Government Services, Inc.
Sponsor class: INDUSTRY
First posted: 2010-11-17
Enrollment: 1968
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Immune response measured by Ross River Vaccine (RRV)-specific neutralizing titer 21 days after the 3rd vaccination as determined by RRV microneutralization (μNT) assay
timeFrame: 21 days after 3rd vaccination
measure: Rate of subjects with a RRV-specific neutralizing titer
timeFrame: 21 days after 3rd vaccination
measure: Frequency and severity of injection site and systemic reactions within 7 days of any study vaccination
timeFrame: Within 7 days of any study vaccination
Secondary outcomes:
measure: Rate of subjects with a RRV-specific neutralizing titer
timeFrame: 21 days after 1st + 2nd vaccination and 180 days after 1st + 3rd vaccination
measure: Rate of subjects with seroconversion
timeFrame: 21 days after 1st, 2nd + 3rd vaccination and 180 days after 1st + 3rd vaccination
measure: Immune response measured by RRV-specific neutralizing titer
timeFrame: 21 days after 1st + 2nd and 180 days after 1st + 3rd vaccination
measure: Fold increase of RRV-specific neutralizing titer
timeFrame: 21 days after 1st, 2nd + 3rd vaccination and 180 days after 1st + 3rd vaccination
measure: Rate of subjects with a RRV-specific immunoglobulin G (IgG) titer
timeFrame: 21 days after 1st, 2nd + 3rd vaccination and 180 days after 1st + 3rd vaccination
measure: Rate of subjects with seroconversion (defined as a positive RRV-specific IgG) titer after vaccination
timeFrame: 21 days after 1st, 2nd + 3rd vaccination and 180 days after 1st + 3rd vaccination
measure: Immune response measured by RRV-specific IgG titer
timeFrame: 21 days after 1st, 2nd + 3rd vaccination and 180 days after 1st + 3rd vaccination
measure: Fold increase of RRV-specific IgG titer
timeFrame: 21 days after 1st, 2nd + 3rd vaccination and 180 days after 1st + 3rd vaccination
measure: Frequency and severity of any systemic reactions
timeFrame: Within first 21 days of study vaccination
measure: Frequency and severity of any injection site reactions
timeFrame: Within first 21 days following a study vaccination
measure: Frequency and severity of any adverse event
timeFrame: During entire study period
measure: Rate of subjects experiencing arthritis associated with one or more of the systemic symptoms consistent with RRV disease
timeFrame: Occurring at least 3 days after vaccination and lasting for more than 3 weeks
Other outcomes:
Locations:
city: Byron Bay
country: Australia
facility: Holdsworth House
state: New South Wales
city: Darlinghurst
country: Australia
facility: Holdsworth House Medical Practice
state: New South Wales
city: Darlinghurst
country: Australia
facility: St. Vincents Hospital
state: New South Wales
city: Westmead
country: Australia
facility: National Centre for Immunisation Research & Surveillance, The Children´s Hospital Westmead
state: New South Wales
city: Auchenflower
country: Australia
facility: AusTrials Pty Limited
state: Queensland
city: Auchenflower
country: Australia
facility: Wesley Research Institute Clinical Trials Centre
state: Queensland
city: Caboolture
country: Australia
facility: AusTrials Pty Limited
state: Queensland
city: Cairns
country: Australia
facility: James Cook University
state: Queensland
city: Herston
country: Australia
facility: Q-Pharm Pty Limited
state: Queensland
city: Herston
country: Australia
facility: QPID Clinical Trials Centre, Royal Children´s Hospital
state: Queensland
city: Bedford Park
country: Australia
facility: Dept of Microbiology & Infectious Diseases
state: South Australia
city: North Adelaide
country: Australia
facility: Melbourne Street
state: South Australia
city: Geelong
country: Australia
facility: Barwon Health - The Geelong Hospital, Dept Clinical & Biomedical Sciences
state: Victoria
city: Heidelberg
country: Australia
facility: Centre for Clinical Studies
state: Victoria
city: Malvern East
country: Australia
facility: Emeritus Research
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
Study officials:
affiliation: Baxter Innovations GmbH
name: Alexander Geisberger, MD
role: STUDY_DIRECTOR
References:
citation: 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.