Safety of a heat-stable rotavirus vaccine among children in Niger: Data from a phase 3, randomized, double-blind, placebo-controlled trial

Coldiron, Matthew E.; Guindo, Ousmane; Makarimi, Rockyath; Seck, Amadou; Garba, Souna; Macher, E; Isanaka, Sheila; Grais, Rebecca F.

doi:10.1016/j.vaccine.2018.05.023

Cited by 18 publications

(62 citation statements)

References 17 publications

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“…In both trials, children were followed for serious adverse events and episodes of acute gastroenteritis; primary analyses were conducted after a target number of cases had been reached. In Niger, the vaccine efficacy against severe rotavirus gastroenteritis was 67% [95% CI: 50–78%; per-protocol analysis at the time of primary analysis (event-driven cut-off)], and no significant differences in adverse event rates were noted in the vaccine as compared with the placebo group, though the study was not powered to evaluate differences in the risk of intussusception [28,51]. In India, the vaccine efficacy against severe rotavirus gastroenteritis in the first year of life was 33% (95% CI: 12–49%; per-protocol analysis).…”

Section: Newly Who-prequalified Rotavirus Vaccinesmentioning

confidence: 99%

Current and new rotavirus vaccines

Burke

Tate

Kirkwood

et al. 2019

Current Opinion in Infectious Diseases

123

158

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Purpose of reviewAs of 2019, four rotavirus vaccines have been prequalified by the WHO for use worldwide. This review highlights current knowledge regarding rotavirus vaccines available, and provides a brief summary of the rotavirus vaccine pipeline.Recent findingsData generated from use of currently available products supports their effectiveness and impact in diverse settings. Rotavirus vaccines have a favorable risk–benefit profile, but previous associations of rotavirus vaccination with intussusception necessitate continued monitoring for this rare but serious adverse event. Implementation of rotavirus vaccines was jeopardized in late 2018 and 2019 by a shortage of vaccine supply. Fortunately, with the prequalification of two additional vaccines in 2018, countries have increased choice in products with different characteristics, pricing, and implementation strategies. Other vaccines currently in development may open up further immunization strategies, such as neonatal vaccination schedules or parenteral administration.SummaryRotavirus vaccines have demonstrated impact in reducing diarrheal morbidity and mortality worldwide. As countries begin to introduce the newly prequalified vaccines, additional data will become available on the safety and effectiveness of those products. Products in the pipeline have distinct profiles and could be an essential part of the expansion of rotavirus vaccine use worldwide.

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Section: Newly Who-prequalified Rotavirus Vaccinesmentioning

confidence: 99%

Current and new rotavirus vaccines

Burke

Tate

Kirkwood

et al. 2019

Current Opinion in Infectious Diseases

123

158

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“…73 Only one case of intussusception was reported, 542 d after receipt of the third dose. 74 The vaccine group experienced 395 serious adverse events, compared to 419 serious adverse events in the placebo group; this difference was not significant. 74 Adverse events between the two groups were comparable, with 1474 (72.1%) participants receiving ROTASIIL and 1456 (71.1%) participants receiving placebo experiencing at least one adverse event (p = .49) in the follow-up period; ROTASIIL was found to be safe.…”

Section: Phase IIImentioning

confidence: 91%

“…72 Secondary outcome measures were rotavirus gastroenteritis, hospitalization due to rotavirus gastroenteritis, hospitalization of any cause (adverse effects or rotavirus gastroenteritis), serious adverse events, and anti-rotavirus IgA sero-response rates and geometric mean titers. [72][73][74] The study found an efficacy of 66.7% (95% CI: 49.9, 77.9) against severe rotavirus gastroenteritis. 73 Only one case of intussusception was reported, 542 d after receipt of the third dose.…”

Section: Phase IIImentioning

confidence: 99%

Product review of the rotavirus vaccines ROTASIIL, ROTAVAC, and Rotavin-M1

Skansberg

Sauer

Tan

et al. 2020

Human Vaccines & Immunotherapeutics

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Rotavirus is the leading cause of severe dehydrating gastroenteritis and death due to diarrhea among children under 5, causing over 180,000 under-5 deaths annually. Safe, effective rotavirus vaccines have been available for over a decade and are used in over 98 countries. In addition to the globally available, WHO-prequalified ROTARIX (GSK) and RotaTeq (Merck), several new rotavirus vaccines have attained national licensure -ROTAVAC (Bharat Biotech) and ROTASIIL (Serum Institute of India), licensed and manufactured in India and now WHO-prequalified, and Rotavin-M1 (PolyVac), licensed and manufactured in Vietnam. In this review, we summarize the available clinical trial and post-introduction evidence for these three new orally administered rotavirus vaccines. All three vaccines have demonstrated safety and efficacy against rotavirus diarrhea, although publicly available preclinical data are limited in some cases. This expanding product landscape presents a range of options to optimize immunization programs, and new presentations of each vaccine are currently under development.

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“…We conducted a double-blind, placebo-controlled randomized phase III event-driven trial in Madarounfa, Niger, to assess the efficacy and safety of Rotasiil (Serum Institute of India, Pune, India) against SRVGE in healthy infants (ClinicalTrials.gov identifier: NCT02145000). Primary efficacy and safety results were previously reported after accumulation of the target number of primary endpoint cases [ 11 , 12 ]. In brief, among the 3,508 infants included in the per-protocol efficacy analysis, there were 31 and 88 cases of SRVGE in the vaccine and placebo group, respectively (2.14 and 6.44 cases per 100 person-years; vaccine efficacy 66.7%, 95% CI 49.9% to 77.9%).…”

Section: Methodsmentioning

confidence: 99%

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

Isanaka

Langendorf²,

McNeal

et al. 2021

PLoS Med

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Background Rotavirus vaccination is recommended in all countries to reduce the burden of diarrhea-related morbidity and mortality in children. In resource-limited settings, rotavirus vaccination in the national immunization program has important cost implications, and evidence for protection beyond the first year of life and against the evolving variety of rotavirus strains is important. We assessed the extended and strain-specific vaccine efficacy of a heat-stable, affordable oral rotavirus vaccine (Rotasiil, Serum Institute of India, Pune, India) against severe rotavirus gastroenteritis (SRVGE) among healthy infants in Niger. Methods and findings From August 2014 to November 2015, infants were randomized in a 1:1 ratio to receive 3 doses of Rotasiil or placebo at approximately 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and graded using the Vesikari score. The primary endpoint was vaccine efficacy of 3 doses of vaccine versus placebo against a first episode of laboratory-confirmed SRVGE (Vesikari score ≥ 11) from 28 days after dose 3, as previously reported. At the time of the primary analysis, median age was 9.8 months. In the present paper, analyses of extended efficacy were undertaken for 3 periods (28 days after dose 3 to 1 year of age, 1 to 2 years of age, and the combined period 28 days after dose 3 to 2 years of age) and by individual rotavirus G type. Among the 3,508 infants included in the per-protocol efficacy analysis (mean age at first dose 6.5 weeks; 49% male), the vaccine provided significant protection against SRVGE through the first year of life (3.96 and 9.98 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 60.3%, 95% CI 43.6% to 72.1%) and over the entire efficacy follow-up period up to 2 years of age (2.13 and 4.69 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 54.7%, 95% CI 38.1% to 66.8%), but the difference was not statistically significant in the second year of life. Up to 2 years of age, rotavirus vaccination prevented 2.56 episodes of SRVGE per 100 child-years. Estimates of efficacy against SRVGE by individual rotavirus genotype were consistent with the overall protective efficacy. Study limitations include limited generalizability to settings with administration of oral polio virus due to low concomitant administration, limited power to assess vaccine efficacy in the second year of life owing to a low number of events among older children, potential bias due to censoring of placebo children at the time of study vaccine receipt, and suboptimal adapted severity scoring based on the Vesikari score, which was designed for use in settings with high parental literacy. Conclusions Rotasiil provided protection against SRVGE in infants through an extended follow-up period of approximately 2 years. Protection was significant in the first year of life, when the disease burden and risk of death are highest, and against a changing pattern of rotavirus strains during the 2-year efficacy period. Rotavirus vaccines that are safe, effective, and protective against multiple strains represent the best hope for preventing the severe consequences of rotavirus infection, especially in resource-limited settings, where access to care may be limited. Studies such as this provide valuable information for the planning of national immunization programs and future vaccine development. Trial registration ClinicalTrials.gov NCT02145000.

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Safety of a heat-stable rotavirus vaccine among children in Niger: Data from a phase 3, randomized, double-blind, placebo-controlled trial

Abstract: ClinicalTrials.gov: NCT02145000.

Cited by 18 publications

References 17 publications

Current and new rotavirus vaccines

Current and new rotavirus vaccines

Product review of the rotavirus vaccines ROTASIIL, ROTAVAC, and Rotavin-M1

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

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