The trial will be a multinational, randomized, double-blind, double-dummy, endpoint driven, group-sequential, active comparator-controlled study, in which participating infants will be randomized 1:1 to receive either: 1) 90 µg of the TV P2-VP8 vaccine IM plus oral placebo, or 2) Rotarix® per os (PO) plus IM placebo. Participants will receive three doses of TV P2-VP8/placebo IM and two doses of Rotarix®/placebo PO at monthly intervals starting at ≥6 to \<8 weeks of age, administered concomitantly with EPI/UIP vaccines. To maintain the blind, infants allocated to the TV P2-VP8 vaccine arm will receive both TV P2-VP8 IM as well as oral placebo vaccine, and infants allocated to receive Rotarix® will receive both Rotarix® PO and placebo IM. Active surveillance for episodes of gastroenteritis (GE) will be conducted throughout the study, through weekly contact with participants' parents. Unsolicited AEs grade ≥ 2 through 28 days after the last study vaccination will be recorded in the study database, as will data for SAEs (including intussusception) throughout the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
8,200
90 µg of the TV P2-VP8 vaccine IM plus oral placebo administered on study days 1, 29 and 57
Rotarix® PO plus IM placebo administered on study days 1, 29 and 57
Centre for Infectious Disease Research in Zambia (CIDRZ)
Lusaka, Zambia
RECRUITINGNumber of laboratory confirmed cases of severe rotavirus gastroenteritis (SRVGE; any strain)
SRVGE is defined by a Vesikari score of \>11 (primary analysis to be performed once \>99 cases are identified with onset at least 2 weeks after receipt of third study vaccination)
Time frame: For cases with onset at least 2 weeks after 3rd study vaccination and onset at any time after first vaccination; for all events within the first 2 years of life
Number of serious adverse events (SAEs), including intussusception
Time frame: Through 28 days after the last dose of study vaccine
Number of Adverse Events (AEs) > or = to grade 2
Time frame: Through 28 days after the last dose of study vaccine
Number of laboratory confirmed cases of very severe rotavirus gastroenteritis (VSRVGE; any strain)
VSRVGE is defined by a Vesikari score of \>15
Time frame: For cases with onset at least 2 weeks after 3rd study vaccination and onset at any time after first vaccination; for all events within the first 2 years of life
Number of P-type specific (P[4], P[6] and P[8]) laboratory confirmed cases of SRVGE and VSRGE
Time frame: For cases with onset at least 2 weeks after 3rd study vaccination and onset at any time after first vaccination; for all events within the first 2 years of life
Number of laboratory confirmed cases of rotavirus gastroenteritis (any strain) of any severity
Time frame: For cases with onset at least 2 weeks after 3rd study vaccination and onset at any time after first vaccination; for all events within the first 2 years of life
Number of laboratory confirmed cases hospitalized for RVGE (any severity)
Time frame: For cases with onset at least 2 weeks after 3rd study vaccination and onset at any time after first vaccination; for all events within the first 2 years of life
Incidence of SRVGE and VSRVGE per 100 children-years
Time frame: For cases with onset at least 2 weeks after 3rd study vaccination and onset at any time after first vaccination; for all events within the first 2 years of life
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