Back to resultsA Phase II Dose-ranging Study of Oral RV3-BB Rotavirus Vaccine
Primary Purpose
Rotavirus Infections
Status
Completed
Phase
Phase 2
Locations
Malawi
Study Type
Interventional
Intervention
RV3-BB
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Rotavirus Infections focused on measuring Dose ranging, Neonatal vaccine, RV3-BB vaccine
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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 EPI vaccines or components are contraindicated.
- 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.
Sites / Locations
- Malawi-Liverpool-Wellcome Trust Clinical Research Programme
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
High dose RV3-BB neonatal schedule
Mid dose RV3-BB neonatal schedule
Low dose RV3-BB neonatal schedule
High dose RV3-BB infant schedule
Arm Description
High 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)
Mid 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)
Low 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)
High 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)
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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.
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
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
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
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
Occurrence of Adverse Events (AE)
Number of Participants with Adverse Events
Occurrence of Serious Adverse Events (SAEs)
Number of participants with Serious Adverse Events (SAEs)
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
Full Information
NCT ID
NCT03483116
First Posted
March 23, 2018
Last Updated
July 6, 2023
Sponsor
Murdoch Childrens Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT03483116
Brief Title
A Phase II Dose-ranging Study of Oral RV3-BB Rotavirus Vaccine
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.
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
June 15, 2018 (Actual)
Primary Completion Date
January 27, 2020 (Actual)
Study Completion Date
January 27, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Murdoch Childrens Research Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rotavirus Infections
Keywords
Dose ranging, Neonatal vaccine, RV3-BB vaccine
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
711 (Actual)
8. Arms, Groups, and Interventions
Arm Title
High dose RV3-BB neonatal schedule
Arm Type
Experimental
Arm Description
High 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)
Arm Title
Mid dose RV3-BB neonatal schedule
Arm Type
Experimental
Arm Description
Mid 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)
Arm Title
Low dose RV3-BB neonatal schedule
Arm Type
Experimental
Arm Description
Low 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)
Arm Title
High dose RV3-BB infant schedule
Arm Type
Experimental
Arm Description
High 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)
Intervention Type
Biological
Intervention Name(s)
RV3-BB
Intervention Description
Oral administration
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Oral administration
Primary Outcome Measure Information:
Title
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
Description
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
Time Frame
At serum collection at approximately 14 weeks of age
Secondary Outcome Measure Information:
Title
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
Description
Defined as a ≥3 fold increase from baseline to 4 weeks after 3 doses of RV3-BB at 18 weeks of age
Time Frame
At serum collection visit approximately 18 weeks of age
Title
Serum Anti Rotavirus IgA Titres in Participants Receiving RV3-BB in a Neonatal or Infant Schedule
Description
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.
Time Frame
At serum collection time points at approximately 14 and 18 weeks of age
Title
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.
Description
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
Time Frame
Sample collections at Week 0 through to approximately 14 and 18 weeks of age
Title
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
Description
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
Time Frame
Sample collections at Week 0 through to approximately 14 and 18 weeks of age
Title
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
Description
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
Time Frame
Sample collections at Week 0 through to approximately 10 and 14 weeks of age
Title
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
Description
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
Time Frame
Sample collections at Week 0 through to approximately 6 and 10 weeks of age
Title
Occurrence of Adverse Events (AE)
Description
Number of Participants with Adverse Events
Time Frame
First dose of investigational product to Study End at approximately 18 weeks of age
Title
Occurrence of Serious Adverse Events (SAEs)
Description
Number of participants with Serious Adverse Events (SAEs)
Time Frame
First dose of investigational product to Study End at approximately 18 weeks of age
Title
Occurrence of Diarrhea. Severe
Description
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
Time Frame
First dose of Investigational product to Study End at approximately 18 weeks of age
10. Eligibility
Sex
All
Minimum Age & Unit of Time
0 Days
Maximum Age & Unit of Time
18 Weeks
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Desiree Witte, MD MTropPaed
Organizational Affiliation
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
Official's Role
Principal Investigator
Facility Information:
Facility Name
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
City
Blantyre
Country
Malawi
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Time Frame
For 24 months from publication of the primary outcome.
IPD Sharing Access Criteria
Data access agreement
Approval by local Ethics committee
Citations:
PubMed Identifier
35065683
Citation
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.
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A Phase II Dose-ranging Study of Oral RV3-BB Rotavirus Vaccine
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