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Trial registered on ANZCTR


Registration number
ACTRN12612001282875
Ethics application status
Approved
Date submitted
4/12/2012
Date registered
12/12/2012
Date last updated
5/09/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
RV3-BB Rotavirus Vaccine Phase IIb Clinical Trial of efficacy, safety and immunogenicity
Scientific title
A Phase IIb, double-blind, randomised, placebo-controlled
parallel group study of the efficacy, safety and
immunogenicity of oral RV3-BB Rotavirus Vaccine,
administered as a neonatal schedule with birth (age 0-5
days) dose, 8-10 and 14-16 week doses or an infant schedule
of 8-10 ,14-16 and 18-20 week doses.
Secondary ID [1] 280937 0
MCRI-RV3-BB-003
Universal Trial Number (UTN)
U1111-1137-4883
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rotavirus gastroenteritis 287032 0
Condition category
Condition code
Infection 287359 287359 0 0
Other infectious diseases
Public Health 288298 288298 0 0
Epidemiology
Oral and Gastrointestinal 288299 288299 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
RV3-BB rotavirus vaccine is 1ml sterile cell-free aqueous solution for oral administration, containing RV3-BB live naturally attenuated human rotavirus particles (at a concentration of 8.3E6 FFU/ml), in cell culture medium containing 10% sucrose.

All participants will receive 4 doses of investigatonal product, at birth (0-5 days), 8-10 weeks, 14-16 weeks and 18-20 weeks of age.

- The neonatal schedule arm will receive active Investigational Product for the 1st, 2nd and 3rd doses and placebo for the 4th dose

- The infant schedule arm will receive placebo for the 1st dose and active Investigational Product for the 2nd, 3rd and 4th doses

- The placebo schedule arm will receve placebo for all 4 doses.
Intervention code [1] 285372 0
Prevention
Comparator / control treatment
Placebo is 1ml sterile cell-free aqueous solution for oral administration, in cell culture medium containing 10% sucrose.

- The placebo schedule arm will receve placebo for all 4 doses.
Control group
Placebo

Outcomes
Primary outcome [1] 287632 0
Episodes of severe rotavirus gastroenteritis (defined as a modified Vesikari score >/=11 and rotavirus antigen detected in stool).
Timepoint [1] 287632 0
From 2 weeks after four doses of investigational product to 18 months of age.
Secondary outcome [1] 298557 0
Efficacy: Episodes of gastroenteritis, rotavirus gastroenteritis (rotavirus antigen detected in stool), and severe gastroenteritis (Vesikari score >/=11)
Timepoint [1] 298557 0
- Combined vaccine group efficacy endpoint from 2 weeks following the fourth dose of investigational product, to 18 months of age.
- Neonatal vs placebo efficacy endpoints from 2 weeks following birth dose until 18 months of age, and 2 weeks following third dose until 18 months of age.
- Infant vs placebo endpoints from 2 weeks following the fourth dose of investigational product, to 18 months of age.
Secondary outcome [2] 298559 0
Immunogenicity (in a subset of participants):
Vaccine Take (defined as serum anti-rotavirus immune response or evidence of vaccine excretion in stool)
Timepoint [2] 298559 0
Timepoint: Serology assessments will be done on serum collected at baseline, after dose 1, dose 3 (full neonatal vaccine schedule) and dose 4 (full infant vaccine schedule). Shedding will be assessed in stool collected in the week after each dose
Secondary outcome [3] 298560 0
Co-administration with Oral Poliovirus vaccine (in a subset of participants): antibody titres to poliovirus.
Timepoint [3] 298560 0
- Antibody titres to poliovirus 28 days following first and
fourth doses of OPV.
Secondary outcome [4] 300258 0
Safety: Unsolicited adverse events)]
Timepoint [4] 300258 0
- Unsolicited AEs occuring within the 28 days following each dose administration.

These events are captured through weekly follow-up of participant and spontaneous reporting (example: upper respiratory tract infection)
Secondary outcome [5] 300259 0
Safety: Solicited symptoms
Timepoint [5] 300259 0
- Solicited systemic and gastrointestinal symptoms within the 7 days following each dose administration. Specifically solicited from participating families using diary cards (examples: loose stool, vomiting)
Secondary outcome [6] 300260 0
Safety: Serious Adverse Events (SAE)
Timepoint [6] 300260 0
- SAEs during the study until 28 days post last dose.

These events are captured through weekly follow-up of participant and spontaneous reporting (example: pneumonia resulting in admission to hospital)
Secondary outcome [7] 300261 0
Safety: Biochemistry (in a subset of participants)
Timepoint [7] 300261 0
- Serum ALT and bilirubin results at each blood collection time point (in a subset of participants).

Assessed: prior to dose 2, 28 days after dose 3, 28 days after dose 4.

Eligibility
Key inclusion criteria
Healthy full-term baby 0 - 5 days of age.
Minimum age
No limit
Maximum age
5 Days
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Major congenital malformations or genetically determined disease, intussusception,
immune system disease, prior receipt of (or exposure in utero to) immunosuppressive therapy, cytotoxic or hepatotoxic drugs, bleeding diathesis, significant evolving neurological disorder, previous anaphylactic reaction, contraindication of EPI vaccines or components, receipt of any other rotavirus vaccine, vomiting, diarrhoea or fever in 24 hours prior to first dose.

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)
Trial site staff will not be aware of the next treatment-arm allocation available. Upon telephone call from trial site staff to randomise a participant, the pharmacy will allocate a number for the participant, using the next number on a randomisation list. Only the pharmacy team will be aware of the treatment-arm allocation associated with each randomisation number.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
3-arm
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 4450 0
Indonesia
State/province [1] 4450 0
Java

Funding & Sponsors
Funding source category [1] 285722 0
Government body
Name [1] 285722 0
National Health and Medical Research Council (NHMRC)
Address [1] 285722 0
Level 1, 16 Marcus Clarke Street
Canberra ACT 2601
Country [1] 285722 0
Australia
Funding source category [2] 286411 0
Charities/Societies/Foundations
Name [2] 286411 0
Bill and Melinda Gates Foundation
Address [2] 286411 0
500 5th Avenue North, Seattle, WA 98109
Country [2] 286411 0
United States of America
Primary sponsor type
Charities/Societies/Foundations
Name
Murdoch Children's Research Institute (MCRI)
Address
Royal Children's Hospital
Flemington Road, Parkville
Victoria 3052
Country
Australia
Secondary sponsor category [1] 284551 0
Commercial sector/Industry
Name [1] 284551 0
Bio Farma
Address [1] 284551 0
PT Bio Farma (Persero)

Jl. Pasteur No. 28 Bandung 40161 Indonesia
Country [1] 284551 0
Indonesia
Other collaborator category [1] 277204 0
University
Name [1] 277204 0
Universitas Gadjah Mada
Address [1] 277204 0
Specific collaborating department:
Paediatric Research Office - UGM
Kantor Penelitian Anak RSUP dr.Sardjito, Jl. Kesehatan No.1, Sekip, Yogyakarta, Indonesia
55281
Country [1] 277204 0
Indonesia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287731 0
Universitas Gadjah Mada Faculty of Medicine Medical and Health Research Ethics Committee
Ethics committee address [1] 287731 0
MEDICAL AND HEALTH RESEARCH ETHICS COMMITTEE
FACULTY OF MEDICINE
UNIVERSITAS GADJAH MADA
Jl. Farmako, Sekip Utara Yogyakarta 55281
Ethics committee country [1] 287731 0
Indonesia
Date submitted for ethics approval [1] 287731 0
Approval date [1] 287731 0
04/07/2012
Ethics approval number [1] 287731 0
KE/FK/465/FC
Ethics committee name [2] 287732 0
Royal Children's Hospital Human Research Ethics Committee
Ethics committee address [2] 287732 0
Royal Children's Hospital, 50 Flemmington Road, Parkville, Victoria, 3052
Melbourne
Ethics committee country [2] 287732 0
Australia
Date submitted for ethics approval [2] 287732 0
Approval date [2] 287732 0
04/07/2012
Ethics approval number [2] 287732 0
32060

Summary
Brief summary
A phase I clinical trial completed in Melbourne in 2011 found the RV3-BB vaccine to be well-tolerated in adults, children and babies 6-8 weeks of age (ACTRN12610000525088).
A phase IIa clinical trial in Dunedin (ACTRN12611001212943) was designed to assess immunogenicity of the vaccine.
The aim of this phase IIb trial is to determine the efficacy of the vaccine. Newborn babies are included in this trial to examine whether administering this vaccine at birth will offer the earliest and possibly greatest protection.
Each of the babies will be randomly assigned to groups, so that two thirds of the babies will receive 3 doses of oral RV3 vaccine and one third of the babies will receive oral doses of placebo. In total each baby’s involvement will include monthly visits and additional regular follow up until 18 months of age.
Trial website
www.mcri.edu.au
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34507 0
Dr Dr Cahya Dewi Satria and Dr Jarir At Thobari
Address 34507 0
Paediatric Research Office
Kantor Penelitian Anak RSUP dr.Sardjito, Jl. Kesehatan No.1, Sekip, Yogyakarta, Indonesia
55281
Country 34507 0
Indonesia
Phone 34507 0
+6287839040006
Fax 34507 0
Email 34507 0
rv3@prougm.org
Contact person for public queries
Name 17754 0
Prof Professor Julie Bines
Address 17754 0
Rotavirus Research Group
Murdoch Childrens Research Institute
Royal Children's Hospital
Flemington Road
Parkville Victoria 3052
Country 17754 0
Australia
Phone 17754 0
+61393454107
Fax 17754 0
Email 17754 0
jebines@unimelb.edu.au
Contact person for scientific queries
Name 8682 0
A/Prof Associate Professor Carl Kirkwood
Address 8682 0
Rotavirus Research Group
Murdoch Childrens Research Institute
Royal Children's Hospital
Flemington Road
Parkville Victoria 3052
Country 8682 0
Australia
Phone 8682 0
+61383416448
Fax 8682 0
Email 8682 0
carl.kirkwood@mcri.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary