Rotavirus Infection of Children
Conditions
Brief summary
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.
Interventions
BIOLOGICALTV P2-VP8
90 µg of the TV P2-VP8 vaccine IM plus oral placebo administered on study days 1, 29 and 57
BIOLOGICALRotarix
Rotarix® PO plus IM placebo administered on study days 1, 29 and 57
Sponsors
Bill and Melinda Gates Foundation
SK Bioscience Co., Ltd.
PATH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
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® PO plus IM placebo.
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 8 Weeks
Healthy volunteers
Yes
Inclusion criteria
* Healthy infants as established by medical history and clinical examination before entering the study * Age: ≥6 and \<8 weeks at the time of first study vaccination (42 days through 55 days old, inclusive, with the day after birth considered 1-day old) * Parental/legal guardian's ability and willingness to provide written informed consent * Intention of the participants' parents to remain in the area with the child during the study period
Exclusion criteria
* Acute disease at the time of first study vaccination - temporary exclusion * Presence of fever on the day of first study vaccination (axillary temperature \>37.6oC) - temporary exclusion * Concurrent participation in another clinical trial throughout the entire timeframe for this study (participation in non-interventional observational study is allowed if there is no blood draw) * Presence of severe malnutrition (weight-for-height z-score ≤-3SD median, per WHO published child growth standards) or any systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) as determined by medical history and/or physical examination that would compromise the participant's health or is likely to result in nonconformance to the protocol * History of premature birth (\<37 weeks gestation) and/or birth weight of \<2.5 kg * History of congenital abdominal disorders, intussusception, or abdominal surgery * Prior receipt of rotavirus vaccine * Known sensitivity or allergy to any components of the study vaccine * Contraindication to any EPI/UIP vaccine * History of anaphylactic reaction * Major congenital or genetic defect * Parents not able, available or willing to accept active weekly follow-up by the study staff * Receipt of any immunoglobulin therapy and/or blood products * Nursing infants whose mother are receiving immunosuppressive biologicals * History of chronic administration (defined as more than 14 days) of immunosuppressant medications, including corticosteroids (those on inhaled or topical steroids may be permitted to participate in the study) * Any medical condition in the participant or parents that, in the judgment of the investigator, would interfere with or serves as a contraindication to protocol adherence or a parents' ability to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of laboratory confirmed cases of severe rotavirus gastroenteritis (SRVGE; any strain) | 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 | 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) |
| Number of serious adverse events (SAEs), including intussusception | Through 28 days after the last dose of study vaccine | — |
| Number of Adverse Events (AEs) > or = to grade 2 | Through 28 days after the last dose of study vaccine | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of laboratory confirmed cases hospitalized for RVGE (any severity) | 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 very severe rotavirus gastroenteritis (VSRVGE; any strain) | 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 | VSRVGE is defined by a Vesikari score of \>15 |
| Incidence of SRVGE and VSRVGE per 100 children-years | 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 | 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 | 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 | — |
Countries
Zambia
Contacts
Primary ContactJoanne Csedrik, RN, MPH
Backup ContactTushar Tewari, MD
Outcome results
None listed