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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Rotavirus Infections

Intervention / Treatment
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* Biological: RV3-BB
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 18 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High dose RV3-BB neonatal schedule<br>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) | Biological: RV3-BB<br>* Oral administration<br>Biological: Placebo<br>* Oral administration<br>|
| Experimental: Mid dose RV3-BB neonatal schedule<br>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) | Biological: RV3-BB<br>* Oral administration<br>Biological: Placebo<br>* Oral administration<br>|
| Experimental: Low dose RV3-BB neonatal schedule<br>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) | Biological: RV3-BB<br>* Oral administration<br>Biological: Placebo<br>* Oral administration<br>|
| Experimental: High dose RV3-BB infant schedule<br>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) | Biological: RV3-BB<br>* Oral administration<br>Biological: Placebo<br>* Oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | At serum collection at approximately 14 weeks of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | At serum collection visit approximately 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. | At serum collection time points at approximately 14 and 18 weeks of age | 
| 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 | Sample collections at Week 0 through to approximately 14 and 18 weeks of age | 
| 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 | Sample collections at Week 0 through to approximately 14 and 18 weeks of age | 
| 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 | Sample collections at Week 0 through to approximately 10 and 14 weeks of age | 
| 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 | Sample collections at Week 0 through to approximately 6 and 10 weeks of age | 
| Occurrence of Adverse Events (AE) | Number of Participants with Adverse Events | First dose of investigational product to Study End at approximately 18 weeks of age | 
| Occurrence of Serious Adverse Events (SAEs) | Number of participants with Serious Adverse Events (SAEs) | First dose of investigational product to Study End at approximately 18 weeks of age | 
| 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 | First dose of Investigational product to Study End at approximately 18 weeks of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dose ranging, Neonatal vaccine, RV3-BB vaccine