Clinical trial NCT02145000: Efficacy and Safety of a Pentavalent Rotavirus Vaccine (BRV-PV) Against Severe Rotavirus Gastroenteritis in Niger
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Severe Rotavirus Gastroenteritis
Keywords: Rotavirus
Gastroenteritis
Diarrhea
Vaccine
Niger
Lead sponsor: Epicentre
Sponsor class: OTHER
Collaborators: name: Medecins Sans Frontieres, Netherlands
name: Serum Institute of India Pvt. Ltd.
name: FORSANI (Forum Santé Niger)
name: Ministère de la Santé Publique, Niger
name: Children's Hospital Medical Center, Cincinnati
First posted: 2014-05-22
Enrollment: 6586
Sex: ALL
Minimum age (years): 6
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

1. known history of congenital abdominal disorders, intussusception, or abdominal surgery
2. receipt of intramuscular, oral, or intravenous corticosteroid treatment within 2 wks
3. receipt or planned administration of a blood transfusion or blood products, including immunoglobulins
4. any known immunodeficiency condition
5. any serious medical condition
6. 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

Primary outcomes:
measure: Laboratory-confirmed episode of severe rotavirus gastroenteritis
timeFrame: 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 outcomes:
measure: Laboratory-confirmed episode of rotavirus gastroenteritis of any severity
timeFrame: 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
measure: Laboratory-confirmed episode of rotavirus gastroenteritis with a Vesikari score of ≥ 17
timeFrame: 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
measure: Laboratory-confirmed episode of severe rotavirus gastroenteritis due to rotavirus serotypes G1, G2, G3, G4 and G9
timeFrame: 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
measure: Episode of gastroenteritis of any cause
timeFrame: 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
measure: Hospitalization due to laboratory-confirmed cases of rotavirus gastroenteritis of any cause
timeFrame: 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
measure: Hospitalization of any cause
timeFrame: 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
measure: Any adverse health event
timeFrame: From the time of Dose 1 to 28 days post-Dose 3
measure: Serious adverse events
timeFrame: From the time of Dose 1 until 2 years of age
measure: Anti-rotavirus IgA sero-response rate
timeFrame: 28 days post-Dose 3
measure: Anti-rotavirus IgA geometric mean titres
timeFrame: 28 days post-Dose 3
Other outcomes:
Locations:
city: Madarounfa
country: Niger
facility: Madarounfa Health District
state: Maradi
Study officials:
affiliation: Epicentre
name: Sheila Isanaka, ScD
role: PRINCIPAL_INVESTIGATOR
affiliation: Epicentre
name: Rebecca Grais, PhD
role: STUDY_DIRECTOR
References:
citation: Sudfeld CR, Bliznashka L, Salifou A, Guindo O, Soumana I, Adehossi I, Langendorf C, Grais RF, Isanaka S. Evaluation of multiple micronutrient supplementation and medium-quantity lipid-based nutrient supplementation in pregnancy on child development in rural Niger: A secondary analysis of a cluster randomized controlled trial. PLoS Med. 2022 May 2;19(5):e1003984. doi: 10.1371/journal.pmed.1003984. eCollection 2022 May.
citation: Kohlmann K, Sudfeld CR, Garba S, Guindo O, Grais RF, Isanaka S. Exploring the relationships between wasting and stunting among a cohort of children under two years of age in Niger. BMC Public Health. 2021 Sep 21;21(1):1713. doi: 10.1186/s12889-021-11689-6.
citation: Isanaka S, Garba S, Plikaytis B, Malone McNeal M, Guindo O, Langendorf C, Adehossi E, Ciglenecki I, Grais RF. Immunogenicity of an oral rotavirus vaccine administered with prenatal nutritional support in Niger: A cluster randomized clinical trial. PLoS Med. 2021 Aug 10;18(8):e1003720. doi: 10.1371/journal.pmed.1003720. eCollection 2021 Aug.
citation: Isanaka S, Langendorf C, McNeal MM, Meyer N, Plikaytis B, Garba S, Sayinzoga-Makombe N, Soumana I, Guindo O, Makarimi R, Scherrer MF, Adehossi E, Ciglenecki I, Grais RF. Rotavirus vaccine efficacy up to 2 years of age and against diverse circulating rotavirus strains in Niger: Extended follow-up of a randomized controlled trial. PLoS Med. 2021 Jul 2;18(7):e1003655. doi: 10.1371/journal.pmed.1003655. eCollection 2021 Jul.
citation: Isanaka S, Kodish SR, Mamaty AA, Guindo O, Zeilani M, Grais RF. Acceptability and utilization of a lipid-based nutrient supplement formulated for pregnant women in rural Niger: a multi-methods study. BMC Nutr. 2019 Jul 1;5:34. doi: 10.1186/s40795-019-0298-3. eCollection 2019.
citation: Coldiron ME, Guindo O, Makarimi R, Soumana I, Matar Seck A, Garba S, Macher E, Isanaka S, Grais RF. Safety of a heat-stable rotavirus vaccine among children in Niger: Data from a phase 3, randomized, double-blind, placebo-controlled trial. Vaccine. 2018 Jun 14;36(25):3674-3680. doi: 10.1016/j.vaccine.2018.05.023. Epub 2018 May 8.
citation: Isanaka S, Guindo O, Langendorf C, Matar Seck A, Plikaytis BD, Sayinzoga-Makombe N, McNeal MM, Meyer N, Adehossi E, Djibo A, Jochum B, Grais RF. Efficacy of a Low-Cost, Heat-Stable Oral Rotavirus Vaccine in Niger. N Engl J Med. 2017 Mar 23;376(12):1121-1130. doi: 10.1056/NEJMoa1609462.