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Rotavirus InfectionsPhase 2NCT03483116

A Phase II Dose-ranging Study of Oral RV3-BB Rotavirus Vaccine

A Phase 2 study testing RV3-BB in people with Rotavirus Infections, run by Murdoch Childrens Research Institute at 1 site in Malawi.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine the serum IgA response of three dose levels of the oral RV3-BB vaccine when administered in a neonatal schedule or when administered as a high dose in an infant schedule. Read more about this study

Who is it for?
Ages 0 days to 18 weeksHealthy volunteers can take part
Conditions the study is for
Rotavirus Infections
What is being tested?
RV3-BB
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
711 participants
Where
1 siteMalawi
Study dates
15 Jun 2018to 27 Jan 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 0 days to 18 weeks
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • Neonate is less than 6 days (≤144 hours) of age at the time of first dose.
  • Neonate is in good health as determined by clinical judgment, including a medical history and physical exam, which confirms the absence of a current or past disease state considered significant by the investigator.
  • Neonate birth weight 2500-4000g inclusive.
  • Neonate's parents/guardians expect to be available for the duration of the study, and agree to adhere to all protocol requirements.
  • Neonate's parents/guardians have provided written informed consent prior to study-related procedures being performed.

Who cannot join

  • Any medical, psychiatric, or social condition of a parent/guardian that in the opinion of the investigator would prevent the neonate's parents/guardians from giving proper informed consent or from complying with the study protocol.
  • Neonates with known or suspected major congenital malformations or genetically determined disease.
  • Neonates with intussusception.
  • Neonates with a known or suspected bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
  • Neonates who have ever received any blood products, including immunoglobulin, or for whom receipt of any blood product during the course of the study is anticipated.
  • Neonates in whom Essential Programme Immunisation (EPI) vaccines or components are contraindicated.
Show all 14Show fewer
  • Neonates who have received or who expect to receive during the study period, any rotavirus vaccine other than those which will be administered as part of this study.
  • Neonates who have ever received, or who are anticipated to receive during the study period, any investigational agent other than those which will be administered as part of this study.
  • Neonates with a previous anaphylactic reaction to any drug, vaccine or vaccine component.
  • Neonates with a significant evolving neurological disorder.
  • Neonates whose parents/guardians are site team employees with direct involvement with the investigators, or who are working on the study.
  • Neonates who have been exposed to immunosuppressive courses of glucocorticosteroids, cytotoxic drugs or blood products through prenatal exposure and/or breast milk in the four weeks prior to randomization.
  • Neonates with diarrhoea or vomiting in the 24 hours preceding randomisation.
  • Neonates with any moderate or severe illness, and/or who have a temperature of ≥37.5˚C axillary/oral or ≥38˚C rectal/tympanic within the 48 hours preceding randomization.

Trial locations and contacts

1 site in 1 country.

Malawi1 site
  • Malawi-Liverpool-Wellcome Trust Clinical Research Programme

    Blantyre

Other trials in Malawi

About this study

Official title: A Phase II Randomized, Double Blind, Parallel Group Dose-ranging Study of Oral RV3-BB Rotavirus Vaccine Administered at a High, Mid and Low Titre as a 3 Dose Neonate Schedule or Administered at a High Titre as a 3 Dose Infant Schedule.

The purpose of this study is to determine the serum IgA response of three dose levels of the oral RV3-BB vaccine when administered in a neonatal schedule or when administered as a high dose in an infant schedule.

Read the detailed description

The primary objective of this study is to assess the cumulative anti-rotavirus serum IgA response (defined as a ≥3 fold increase from baseline) 4 weeks after 3 doses of RV3-BB administered in a neonatal schedule at a High, Mid or low vaccine titre. In addition the cumulative anti-rotavirus serum IgA response (defined as a ≥3 fold increase from baseline) 4 weeks after 3 doses of RV3-BB administered in an infant schedule at a high dose of vaccine will be assessed along with cumulative vaccine take and components of vaccine take after 3 doses of RV3-BB administered in a neonatal or infant schedule.

The safety and tolerability of RV3-BB when administered as an infant or as a neonatal schedule will be described.

Being tested
RV3-BB, Placebo
Keywords
Dose ranging, Neonatal vaccine, RV3-BB vaccine
Medical subject headings
Rotavirus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RV3-BBBiological

    Oral administration

  • PlaceboBiological

    Oral administration

Study groups in NCT03483116
Study groupRoleWhat they receive
High dose RV3-BB neonatal scheduleExperimentalHigh dose neonatal RV3-BB vaccine schedule. RV3-BB Vaccine for Investigational product doses 1 (0-5 days), 2 (week 6) and 3 (week 10) and placebo for Investigational product dose 4 (week 14)
Receives: Biological: RV3-BB; Biological: Placebo
Mid dose RV3-BB neonatal scheduleExperimentalMid dose neonatal RV3-BB vaccine schedule. RV3-BB Vaccine for Investigational product doses 1 (0-5 days), 2 (week 6) and 3 (week 10) and placebo for Investigational product dose 4 (week 14)
Receives: Biological: RV3-BB; Biological: Placebo
Low dose RV3-BB neonatal scheduleExperimentalLow dose neonatal RV3-BB vaccine schedule. RV3-BB Vaccine for Investigational product doses 1 (0-5 days), 2 (week 6) and 3 (week 10) and placebo for Investigational product dose 4 (week 14)
Receives: Biological: RV3-BB; Biological: Placebo
High dose RV3-BB infant scheduleExperimentalHigh dose infant RV3-BB vaccine schedule. Placebo for Investigational product dose 1 (0-5 days) and RV3-BB Vaccine for Investigational product doses 2 (week 6) 3 (week 10) and dose 4 (week 14)
Receives: Biological: RV3-BB; Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With a Cumulative Anti Rotavirus Serum Immunoglobulin A (IgA) Response (≥3 Fold Increase From Baseline) in Neonatal Vaccine Schedule at High Mid and Low Dose of RV3-BB

    Cumulative anti rotavirus serum Immunoglobulin A (IgA) response is defined as a ≥3 fold increase from baseline at each serum collection time point to 4 weeks after 3 doses of RV3-BB

    Measured: At serum collection at approximately 14 weeks of age

Secondary outcomes (9)
  1. Number of Participants With a Cumulative Anti Rotavirus Serum IgA Response (≥3 Fold Increase From Baseline) After 3 Doses in an Infant RV3-BB Schedule

    Defined as a ≥3 fold increase from baseline to 4 weeks after 3 doses of RV3-BB at 18 weeks of age

    Measured: At serum collection visit approximately 18 weeks of age

  2. Serum Anti Rotavirus IgA Titres in Participants Receiving RV3-BB in a Neonatal or Infant Schedule

    Expressed as geometric mean titres (GMTs) from baseline to post dose 3 of RV3-BB Minimum 10 Maximum 250,000 Higher score considered to be immunogenic.

    Measured: At serum collection time points at approximately 14 and 18 weeks of age

  3. Number of Participants With a Cumulative "Vaccine Take" (Serum Anti Rotavirus IgA Response or Shedding of RV3-BB Vaccine Virus) and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High Dose of RV3-BB.

    Vaccine take is defined as at least a threefold increase in serum anti-rotavirus immunoglobulin A (IgA) from baseline to post Investigational product dosing, or detectable RV3 shedding in stools (by ELISA or PCR) any day from day three to day five following administration of Investigational product. Cumulative vaccine take is defined as Vaccine take observed at the current assessment time point or following any previous dose

    Measured: Sample collections at Week 0 through to approximately 14 and 18 weeks of age

  4. Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a Mid or Low Dose of RV3-BB

    Vaccine take is defined as at least a threefold increase in serum anti-rotavirus immunoglobulin A (IgA) from baseline to post Investigational Product dosing, or detectable RV3 shedding in stools (by ELISA or PCR) any day from day three to day five following administration of Investigational product. Cumulative vaccine take is defined as Vaccine take observed at the current assessment time point or following any previous dose

    Measured: Sample collections at Week 0 through to approximately 14 and 18 weeks of age

  5. Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 2 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB

    Vaccine take is defined as at least a threefold increase in serum anti-rotavirus immunoglobulin A (IgA) from baseline to post Investigational product dosing, or detectable RV3 shedding in stools (by ELISA or PCR) any day from day three to day five following administration of Investigational product. Cumulative vaccine take is defined as Vaccine take observed at the current assessment time point or following any previous dose

    Measured: Sample collections at Week 0 through to approximately 10 and 14 weeks of age

  6. Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 1 Dose of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB

    Vaccine take is defined as at least a threefold increase in serum anti-rotavirus immunoglobulin A (IgA) from baseline to post Investigational product dosing, or detectable RV3 shedding in stools (by ELISA or PCR) any day from day three to day five following administration of Investigational product. Cumulative vaccine take is defined as Vaccine take observed at the current assessment time point or following any previous dose

    Measured: Sample collections at Week 0 through to approximately 6 and 10 weeks of age

  7. Occurrence of Adverse Events (AE)

    Number of Participants with Adverse Events

    Measured: First dose of investigational product to Study End at approximately 18 weeks of age

  8. Occurrence of Serious Adverse Events (SAEs)

    Number of participants with Serious Adverse Events (SAEs)

    Measured: First dose of investigational product to Study End at approximately 18 weeks of age

  9. Occurrence of Diarrhea. Severe

    Diarrhea will be described according to severity and detection of wild type rotavirus in diarrhea samples collected. Severity defined using a modified version of the Vesikari clinical score for gastroenteritis. Severed is modified Vesikari score of greater than or equal to 11.

    The Vesikari scale is a 20-point scale based on duration and peak frequency of diarrhea and vomiting, degree of temperature, severity of dehydration, and treatment provided to the patient (i.e., rehydration or hospitalization). This scale is divided into three ranges: mild <7, moderate 7-10, and severe ≥11

    Measured: First dose of Investigational product to Study End at approximately 18 weeks of age

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Mar 2018
  2. Study start15 Jun 2018
  3. Primary completion27 Jan 2020
  4. Study completion27 Jan 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is a Phase II, randomised, double-blind, placebo-controlled, four-arm parallel group study of two different dosing schedules of oral RV3-BB
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
711 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03483116
Sponsor's protocol ID
MCRI-RV3-BB-004
Status last verified
Jul 2023
First submitted
23 Mar 2018
Last updated
10 Jul 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Deidentified group data may be available for sharing on application to the Sponsor. This application must include the relevant proposal detailing the intended use of the data, the Ethics approval for this proposal and requires a signed data sharing agreement. Additional study documents including the study protocol, statistical analysis plan and informed consent are available on application to the Sponsor.

Publications

  • Witte D, Handley A, Jere KC, Bogandovic-Sakran N, Mpakiza A, Turner A, Pavlic D, Boniface K, Mandolo J, Ong DS, Bonnici R, Justice F, Bar-Zeev N, Iturriza-Gomara M, Ackland J, Donato CM, Cowley D, Barnes G, Cunliffe NA, Bines JE. Neonatal rotavirus vaccine (RV3-BB) immunogenicity and safety in a neonatal and infant administration schedule in Malawi: a randomised, double-blind, four-arm parallel group dose-ranging study. Lancet Infect Dis. 2022 May;22(5):668-678. doi: 10.1016/S1473-3099(21)00473-4. Epub 2022 Jan 20.

    PubMed 35065683
  • Morgan B, Lyons EA, Handley A, Bogdanovic-Sakran N, Pavlic D, Witte D, Mandolo J, Turner A, Jere KC, Justice F, Ong DS, Bonnici R, Boniface K, Donato CM, Mpakiza A, Meyer A, Bar-Zeev N, Iturriza-Gomara M, Cunliffe NA, Danchin M, Bines JE. Rotavirus-Specific Maternal Serum Antibodies and Vaccine Responses to RV3-BB Rotavirus Vaccine Administered in a Neonatal or Infant Schedule in Malawi. Viruses. 2024 Sep 19;16(9):1488. doi: 10.3390/v16091488.

    PubMed 39339964

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RV3-BB in people with Rotavirus Infections, run by Murdoch Childrens Research Institute at 1 site in Malawi.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Malawi. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With a Cumulative Anti Rotavirus Serum Immunoglobulin A (IgA) Response (≥3 Fold Increase From Baseline) in Neonatal Vaccine Schedule at High Mid and Low Dose of RV3-BB (time frame: At serum collection at approximately 14 weeks of age). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03483116, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2023.

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