Clinical trial NCT03483116: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rotavirus Infections
Keywords: Dose ranging
Neonatal vaccine
RV3-BB vaccine
Lead sponsor: Murdoch Childrens Research Institute
Sponsor class: OTHER
First posted: 2018-03-30
Enrollment: 711
Sex: ALL
Minimum age (years): 0
Maximum age (years): 18
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
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
timeFrame: At serum collection at approximately 14 weeks of age
Secondary outcomes:
measure: 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
timeFrame: At serum collection visit approximately 18 weeks of age
measure: Serum Anti Rotavirus IgA Titres in Participants Receiving RV3-BB in a Neonatal or Infant Schedule
timeFrame: At serum collection time points at approximately 14 and 18 weeks of age
measure: 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.
timeFrame: Sample collections at Week 0 through to approximately 14 and 18 weeks of age
measure: 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
timeFrame: Sample collections at Week 0 through to approximately 14 and 18 weeks of age
measure: 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
timeFrame: Sample collections at Week 0 through to approximately 10 and 14 weeks of age
measure: 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
timeFrame: Sample collections at Week 0 through to approximately 6 and 10 weeks of age
measure: Occurrence of Adverse Events (AE)
timeFrame: First dose of investigational product to Study End at approximately 18 weeks of age
measure: Occurrence of Serious Adverse Events (SAEs)
timeFrame: First dose of investigational product to Study End at approximately 18 weeks of age
measure: Occurrence of Diarrhea. Severe
timeFrame: First dose of Investigational product to Study End at approximately 18 weeks of age
Other outcomes:
Locations:
city: Blantyre
country: Malawi
facility: Malawi-Liverpool-Wellcome Trust Clinical Research Programme
Study officials:
affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme
name: Desiree Witte, MD MTropPaed
role: PRINCIPAL_INVESTIGATOR
References:
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.