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

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

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

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.

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.