Optimising Rotavirus Vaccine in Aboriginal Children

NCT02941107 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: CVID/2015-03
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

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.

Conditions

Viral Gastroenteritis Due to Rotavirus

Keywords

Aboriginal; Rotavirus; Vaccine; Diarrhoea

Outcome Measures

Primary Outcomes (2)

• Time from randomisation to medical attendance for acute gastroenteritis or acute diarrhoea illness

  Time from randomisation to medical attendance (hospitalisation, emergency department presentation, medical clinic presentation) for which the primary reason for presentation is presumed or confirmed acute gastroenteritis or acute diarrhoea illness between randomisation and age 36 months.

  Randomisation to 36 months

• Occurrence of anti-rotavirus IgA seroconversion

  Anti-rotavirus IgA seroconversion, defined as serum anti-rotavirus IgA \> 20U/ ml 28 to 55 days post RV1/placebo among infants with anti-rotavirus serum IgA \< 20U/ ml before RV1/placebo, to be summarised as the proportion of all children per group.

  28-55 Days post RV1/placebo administration

Secondary Outcomes (7)

• Time from randomisation to hospitalisation for acute gastroenteritis or acute diarrhoea illness

  Randomisation to 36 months

• Time from randomisation to hospitalisation for rotavirus confirmed diarrhoea illness

  Randomisation to 36 months

• Time from randomisation to Rotavirus infection

  Randomisation to 36 months

• Change in anti-rotavirus IgA log titre between administration of intervention (RV1/placebo) and 28 to 55 days post dose

  Randomisation and 28-55 days post RV1/placebo administration

• Occurrence of intussusception fulfilling Brighton criteria (see Appendix A)

  Within the first 28 days of RV1/placebo administration

Study Arms (2)

Rotarix

EXPERIMENTAL

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

Drug: Rotarix (RV1)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Rotarix (RV1) DRUG

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.

Also known as: ROTARIX™

Rotarix

Placebo DRUG

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.

Also known as: Viscosweet

Placebo

Eligibility Criteria

• Age: 6 Months - 12 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Telethon Kids Institute: lead
• Menzies School of Health Research: collaborator

Study Sites (1)

Menzies School of Health Research

Darwin, Northern Territory, 0810, Australia

Location

Related Publications (3)

• 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.

  PMID: 35134951 DERIVED

• 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.

  PMID: 32843086 DERIVED

• 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.

  PMID: 31727664 DERIVED

MeSH Terms

Conditions

Diarrhea

Interventions

RIX4414 vaccine

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Tom Snelling

  Telethon Kids Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2016
• First Posted: October 21, 2016
• Study Start: March 27, 2018
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 6, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: post publication of study results
• Access Criteria: Researchers need to supply a statistical analysis plan and appropriate Ethics approvals

Locations

AU (1)