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

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

Randomized, Double-blind, Placebo-controlled Phase III Clinical Trial to Assess the Efficacy and Safety of a Pentavalent Rotavirus Vaccine (BRV-PV) Against Severe Rotavirus Gastroenteritis Among Infants in Niger

Medecins Sans Frontieres, Netherlands, Serum Institute of India Pvt. Ltd., FORSANI (Forum Santé Niger), Ministère de la Santé Publique, Niger, Children's Hospital Medical Center, Cincinnati

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.

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.

Three doses of BRV-PV containing ≥ Log10 5.6 FFU/Dose of each serotype G1, G2, G3, G4 and G9, or placebo, will be administered at 4 week intervals between doses (with a window of -1 to +4 weeks). The first administration will occur at 6-8 weeks of age.

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

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

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

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

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

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

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

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