A Trial to Assess the Safety, Immunogenicity and Efficacy of a Trivalent Rotavirus P2-VP8 Subunit Vaccine in Prevention of Severe Rotavirus Gastroenteritis in Healthy Infants in Africa and India

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3 Double-blind, Randomized, Active Comparator-controlled, Group-sequential, Multinational Trial to Assess the Safety, Immunogenicity and Efficacy of a Trivalent Rotavirus P2-VP8 Subunit Vaccine in Prevention of Severe Rotavirus Gastroenteritis in Healthy Infants

Conditions
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Rotavirus Infection of Children

Intervention / Treatment
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* Biological: TV P2-VP8
* Biological: Rotarix


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 8 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TV P2-VP8<br> | Biological: TV P2-VP8<br>* 90 µg of the TV P2-VP8 vaccine IM plus oral placebo administered on study days 1, 29 and 57<br>|
| Active Comparator: Rotarix®<br> | Biological: Rotarix<br>* Rotarix® PO plus IM placebo administered on study days 1, 29 and 57<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number 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) | 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 |  | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of laboratory confirmed cases of very severe rotavirus gastroenteritis (VSRVGE; any strain) | VSRVGE is defined by a Vesikari score of >15 | 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 | 
| 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 | 
| 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 |