A Clinical Trial to Study the Effect and Safety of Rotavirus Vaccine Against Severe Rotavirus Gastroenteritis in Healthy Indian Infants

Study Overview
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Brief Summary
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This is a Phase 3 multicentre, randomized, double blind, placebo-controlled study to determine the effectiveness of the rotavirus vaccine.

Detailed Description
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The hypothesis is that a three dose series of BRV-PV administered orally to healthy Indian infants, with the initial dose given at 6-8 weeks of age and followed by vaccinations at monthly intervals, will significantly reduce the incidence of severe rotavirus gastroenteritis (SRVGE). Duration of follow-up is until aged 2 years of each enrolled child. The study is powered to detect vaccine efficacy significantly greater than 10% (95% confidence interval lower bound > 10%) if the true vaccine efficacy is 50% or higher.

Official Title
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Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Live Attenuated Bovine-Human Rotavirus Reassortant Pentavalent Vaccine (BRV-PV) Against Severe Rotavirus Gastroenteritis in Healthy Indian Infants

Conditions
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Rotavirus Gastroenteritis

Intervention / Treatment
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* Biological: Live Attenuated Pentavalent (G1-G2-G3-G4-G9) Human X Bovine Reassortant Rotavirus Vaccine (BRV-PV)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy infants as established by medical history and clinical examination before entering the study. Age: 6-8 weeks at the time of enrollment. Parental ability and willingness to provide informed consent. Parent who intends to remain in the area with the child during the study period. Exclusion Criteria: Presence of diarrhea or vomiting in the previous 72 hours or on the day of enrollment (temporary exclusion) Presence of fever on the day of enrollment (temporary exclusion). Acute disease at the time of enrollment (temporary exclusion) Concurrent participation in another clinical trial throughout the entire timeframe for this study. Presence of significant malnutrition (weight-for-height z-score <-3SD median) or any systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) as determined by medical history and/or physical examination which would compromise the subject's health or is likely to result in nonconformance to the protocol. History of congenital abdominal disorders, intussusception or abdominal surgery Known or suspected impairment of immunological function based on medical history and physical examination. Household contact with an immunosuppressed individual or pregnant woman. Prior receipt of rotavirus vaccine. A known sensitivity or allergy to any components of the study vaccine. Major congenital or genetic defect. History of persistent diarrhea (defined as diarrhea more than 14 days). Participant's parents not able, available or willing to accept active weekly follow-up by the study staff. Has received any immunoglobulin therapy and/or blood products since birth or planned administration during the study period. History of chronic administration (defined as more than 14 days) of immunosuppressants including corticosteroids. Infants on inhaled or topical steroids may be permitted to participate in the study. History of any neurologic disorders or seizures. Any medical condition in the parents/infant which, in the judgment of the investigator, would interfere with or serves as a contraindication to protocol adherence or a participant's parents' ability to give informed consent.

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 8 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccine Arm<br>3 doses, 4 weeks apart, of Live Attenuated Pentavalent (G1-G2-G3-G4-G9) Human X Bovine Reassortant Rotavirus Vaccine (BRV-PV), at a dosage of ≥ Log10^5.6 fluorescent focus units (FFU)/Serotype/Dose in 2.5 ml of buffered diluent | Biological: Live Attenuated Pentavalent (G1-G2-G3-G4-G9) Human X Bovine Reassortant Rotavirus Vaccine (BRV-PV)<br>* Live Attenuated Pentavalent (G1-G2-G3-G4-G9) Human X Bovine Reassortant Rotavirus Vaccine (BRV-PV), at a dosage of ≥ Log10^5.6 fluorescent focus units (FFU)/Serotype/Dose in 2.5 ml of buffered diluent<br>|
| Placebo Comparator: Placebo group<br>3 doses, 4 weeks apart, of Lyophilized minimal essential medium (MEM) + excipients reconstituted in 2.5 ml of buffered diluents | Other: Placebo<br>* Lyophilized minimal essential medium (MEM) + excipients reconstituted in 2.5 ml of buffered diluents<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| occurrence of Severe Rotavirus Gastroenteritis | Laboratory confirmed cases of severe rotavirus gastroenteritis occurring in infants receiving the complete vaccination regimen occurring from 14 days after the third vaccine dose until 122 cases are accrued, or until all participating infants reach two years of age (per protocol analysis). | Up to 2 years of age of participants | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Occurrence of SAE Solicited post-vaccination reactions SAEs Severe AEs Unsolicited AEs Intussusception Death | Until completion of 2 years age of participant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rotavirus, rotavirus vaccine, BRV-PV