Efficacy and Safety of a Pentavalent Rotavirus Vaccine (BRV-PV) Against Severe Rotavirus Gastroenteritis in Niger

Phase 3

Completed

Brief Summary: The study is a double-blinded, randomized, placebo-controlled, trial with two groups of infants receiving vaccine or placebo to assess the efficacy and safety of BRV-PV. Three doses of BRV-PV containing ≥ Log10 5.6 FFU/Dose of each serotype G1, G2, G3, G4 and G9 will be administered at 4 week intervals between doses. The first administration will occur at 6-8 weeks of age.

We hypothesize a difference in vaccine efficacy of three doses of BRV-PV vaccine vs. placebo against severe rotavirus gastroenteritis in healthy infants in Niger.

Active surveillance for gastroenteritis episodes will be conducted throughout the trial. Surveillance for adverse events will be carried out among all children from the time of first vaccination and 28 days post-Dose 3. Surveillance for all serious adverse events, including intussusception and death, will be conducted on all participants until they each reach two years of age.

To assess the effect of prenatal nutrition supplementation on infant immune response to the BRV-PV vaccine, study villages in the immunogenicity sub-cohort will be randomized in a 1:1:1 ratio to provide pregnant women with daily iron-folate, multiple micronutrients or a lipid-based nutrition supplement. Infants of participating women, if eligible at 6-8 weeks of age, will be randomized in a 1:1 ratio to receive three doses of vaccine or placebo and enter the main trial as part of the immunogenicity sub-cohort.

Recruitment & Eligibility

Inclusion Criteria

aged 6-8 weeks at the time of inclusion
able to swallow and no history of vomiting within 24 hours
resident in Madarounfa Health District and within the catchment area of the central health facility
intending to remain in the study area for 2 years
parent/guardian providing written informed consent

Exclusion Criteria

Any of the following will exclude an infant from randomization in the study:

known history of congenital abdominal disorders, intussusception, or abdominal surgery
receipt of intramuscular, oral, or intravenous corticosteroid treatment within 2 wks
receipt or planned administration of a blood transfusion or blood products, including immunoglobulins
any known immunodeficiency condition
any serious medical condition
any other condition in which, in the judgment of the investigator, would interfere with or serves as a contraindication to protocol adherence or the parent/guardian's ability to give informed consent

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Same constituents as the active vaccine but without the viral antigens; manufactured by SIIL.
Rotavirus vaccine (BRV-PV)	Rotavirus vaccine (BRV-PV)	Live attenuated bovine-human \[UK\] reassortant rotavirus vaccine manufactured by the Serum Institute of India, Limited (SIIL). The pentavalent vaccine (BRV-PV) contains rotavirus serotypes G1, G2, G3, G4, and G9 (≥5.6 log10 FFU/serotype/dose). The vaccine is in lyophilized form and supplied with 2.5 ml of citrate bicarbonate buffer that is added for reconstitution just before oral administration.

Primary Outcome Measures

Name	Time	Method
Laboratory-confirmed episode of severe rotavirus gastroenteritis	From 28 days post-Dose 3 until 117 cases are accrued or when all participating infants reach 2 years of age if 117 cases are not attained

Secondary Outcome Measures

Name	Time	Method
Laboratory-confirmed episode of rotavirus gastroenteritis with a Vesikari score of ≥ 17	From 28 days post-Dose 3 to 1 year of age, from 1 to 2 years of age, and from 28 days post-Dose 3 to 2 years of age
Episode of gastroenteritis of any cause	From 28 days post-Dose 3 to 1 year of age, from 1 to 2 years of age, and from 28 days post-Dose 3 to 2 years of age
Hospitalization of any cause	From 28 days post-Dose 3 to 1 year of age, from 1 to 2 years of age, and from 28 days post-Dose 3 to 2 years of age
Serious adverse events	From the time of Dose 1 until 2 years of age
Anti-rotavirus IgA sero-response rate	28 days post-Dose 3
Laboratory-confirmed episode of rotavirus gastroenteritis of any severity	From 28 days post-Dose 3 to 1 year of age, from 1 to 2 years of age, and from 28 days post-Dose 3 to 2 years of age
Laboratory-confirmed episode of severe rotavirus gastroenteritis due to rotavirus serotypes G1, G2, G3, G4 and G9	From 28 days post-Dose 3 to 1 year of age, from 1 to 2 years of age, and from 28 days post-Dose 3 to 2 years of age
Hospitalization due to laboratory-confirmed cases of rotavirus gastroenteritis of any cause	From 28 days post-Dose 3 to 1 year of age, from 1 to 2 years of age, and from 28 days post-Dose 3 to 2 years of age
Any adverse health event	From the time of Dose 1 to 28 days post-Dose 3
Anti-rotavirus IgA geometric mean titres	28 days post-Dose 3