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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02941107




Registration number
NCT02941107
Ethics application status
Date submitted
19/10/2016
Date registered
21/10/2016
Date last updated
6/03/2024

Titles & IDs
Public title
Optimising Rotavirus Vaccine in Aboriginal Children
Scientific title
The ORVAC Trial: A Phase IV, Double-blind, Randomised, Placebo-controlled Clinical Trial of a Third Scheduled Dose of RV1 Rotavirus Vaccine in Australian Indigenous Infants to Improve Protection Against Gastroenteritis
Secondary ID [1] 0 0
CVID/2015-03
Universal Trial Number (UTN)
Trial acronym
ORVAC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Viral Gastroenteritis Due to Rotavirus 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Rotarix (RV1)
Treatment: Drugs - Placebo

Experimental: Rotarix - Rotarix (RV1) vaccine, 1mL liquid suspension administered orally.

Placebo comparator: Placebo - Placebo liquid suspension manufactured to mimic Rotarix (RV1) vaccine, 1ml administered orally


Treatment: Drugs: Rotarix (RV1)
ROTARIX™ (RV1) is a live-attenuated human monovalent oral vaccine containing attenuated G1P\[8\] human rotavirus strain sponsored and distributed in Australia by GlaxoSmithKline Biologicals where it is licensed for the prevention of rotavirus gastroenteritis.

Treatment: Drugs: Placebo
The placebo for this trial will be Viscosweet, a clear and flavoured solution used as a pharmaceutical excipient repackaged into a labelled syringe identical to the active and firmly sealed with an end cap.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time from randomisation to medical attendance for acute gastroenteritis or acute diarrhoea illness
Timepoint [1] 0 0
Randomisation to 36 months
Primary outcome [2] 0 0
Occurrence of anti-rotavirus IgA seroconversion
Timepoint [2] 0 0
28-55 Days post RV1/placebo administration
Secondary outcome [1] 0 0
Time from randomisation to hospitalisation for acute gastroenteritis or acute diarrhoea illness
Timepoint [1] 0 0
Randomisation to 36 months
Secondary outcome [2] 0 0
Time from randomisation to hospitalisation for rotavirus confirmed diarrhoea illness
Timepoint [2] 0 0
Randomisation to 36 months
Secondary outcome [3] 0 0
Time from randomisation to Rotavirus infection
Timepoint [3] 0 0
Randomisation to 36 months
Secondary outcome [4] 0 0
Change in anti-rotavirus IgA log titre between administration of intervention (RV1/placebo) and 28 to 55 days post dose
Timepoint [4] 0 0
Randomisation and 28-55 days post RV1/placebo administration
Secondary outcome [5] 0 0
Occurrence of intussusception fulfilling Brighton criteria (see Appendix A)
Timepoint [5] 0 0
Within the first 28 days of RV1/placebo administration
Secondary outcome [6] 0 0
Occurrence of a serious adverse event
Timepoint [6] 0 0
Randomisation to 36 months
Secondary outcome [7] 0 0
Medical attendance for confirmed acute gastroenteritis or acute diarrhoea illness between randomisation and 36 months gastroenteritis or acute diarrhoea illness.
Timepoint [7] 0 0
Randomisation to 36 months

Eligibility
Key inclusion criteria
* Aged = 6 months and < 12 months
* Identified as Aboriginal and/or Torres Strait Islander and/or South Sea Islander per attending legally responsible care-giver/parent.
* Have received either one or two prior doses of RV1 vaccination as confirmed by checking the immunisation register.
* Legally responsible care-giver/parent is willing for their infant to participate in the study and is aware of the requirements of the protocol.
* Legally responsible care-giver/parent is willing to allow other parties involved in the treatment of their child (including general practitioner, medical centre staff and any other medical professionals the child may be a patient of for the duration of the trial) to be notified of their participation in the trial and for participation in the trial to be recorded within the Northern Territory Immunisation Register.
* The legally responsible care-giver/parent is willing to allow the study team to obtain a vaccination history from Northern Territory Immunisation Register and/or the Australian Childhood Immunisation Register (ACIR) and/or local provider.
* The legally responsible care-giver/parent is willing to allow the study team to obtain a medical history from hospitalisation and laboratory databases, the disease notification register, the participant's electronic medical records and/or from the participant's primary care provider for the period from enrolment to age 36 months
* Informed consent for the infant's/child's participation in the study has been given by the legally responsible care-giver/parent
Minimum age
6 Months
Maximum age
12 Months
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Has any contraindication for RV1 vaccination including:

* Severe combined immunodeficiency, any history of intussusception, any history of hypersensitivity to any vaccine component, or an uncorrected gastrointestinal tract malformation, receipt of more than two weeks of immunosuppressant or immune modifying drugs, (e.g. prednisolone > 0.5mg/kg/day) within 28 days of enrolment, confirmed or suspected severe immunosuppressive or immunodeficient conditions, including human immunodeficiency virus (HIV) infection
* Receipt of any rotavirus vaccination other than RV1
* Receipt in the previous 3 months of any blood products including immunoglobulin
* Has received no prior doses or > two prior doses of RV1 vaccination
* Medical condition or treatment with medication which in the opinion of the clinic staff would make the child unsuitable for the trial
* Previously enrolled in the trial

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/03/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2026
Actual
Sample size
Target
1000
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NT
Recruitment hospital [1] 0 0
Menzies School of Health Research - Darwin
Recruitment postcode(s) [1] 0 0
0810 - Darwin

Funding & Sponsors
Primary sponsor type
Other
Name
Telethon Kids Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Menzies School of Health Research
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Australian Indigenous children, particularly those living in remote communities, suffer a disproportionately high burden of rotavirus gastroenteritis disease. Despite the introduction of rotavirus vaccine into the Northern Territory (NT) Immunisation Schedule in 2006, the rate of hospitalization for rotavirus in NT Aboriginal children \< 5 years continues to be high, and the rate ratio of rotavirus hospitalisations for Indigenous versus non-Indigenous children has actually increased. The reasons for sub-optimal vaccine response are not completely understood, but both reduced vaccine immune responses and low vaccine coverage are likely to be important factors.

The purpose of this study is to determine if Aboriginal children who receive an additional dose of RV1 between the ages of 6 and 12 months, will have an increase anti-rotavirus serum IgA seroconversion and decreased medical presentations with gastroenteritis in the first three years of life, compared to those who receive placebo.
Trial website
https://clinicaltrials.gov/study/NCT02941107
Trial related presentations / publications
Middleton BF, Danchin M, Jones MA, Leach AJ, Cunliffe N, Kirkwood CD, Carapetis J, Gallagher S, Kirkham LA, Granland C, McNeal M, Marsh JA, Waddington CS, Snelling TL. Immunogenicity of a Third Scheduled Dose of Rotarix in Australian Indigenous Infants: A Phase IV, Double-blind, Randomized, Placebo-Controlled Clinical Trial. J Infect Dis. 2022 Nov 1;226(9):1537-1544. doi: 10.1093/infdis/jiac038.
Jones MA, Graves T, Middleton B, Totterdell J, Snelling TL, Marsh JA. The ORVAC trial: a phase IV, double-blind, randomised, placebo-controlled clinical trial of a third scheduled dose of Rotarix rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis: a statistical analysis plan. Trials. 2020 Aug 26;21(1):741. doi: 10.1186/s13063-020-04602-w.
Middleton BF, Jones MA, Waddington CS, Danchin M, McCallum C, Gallagher S, Leach AJ, Andrews R, Kirkwood C, Cunliffe N, Carapetis J, Marsh JA, Snelling T. The ORVAC trial protocol: a phase IV, double-blind, randomised, placebo-controlled clinical trial of a third scheduled dose of Rotarix rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis. BMJ Open. 2019 Nov 14;9(11):e032549. doi: 10.1136/bmjopen-2019-032549.
Public notes

Contacts
Principal investigator
Name 0 0
Tom Snelling
Address 0 0
Telethon Kids Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02941107