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

NCT04010448 | Unknown Phase 3 DMC

• 1 other identifier: CVIA 061
• Study Type: interventional
• Target: 8,200
• Locations: 1 country
• Sites: 1

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.

Conditions

Rotavirus Infection of Children

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• 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

• 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

Study Arms (2)

TV P2-VP8

EXPERIMENTAL

Biological: TV P2-VP8

Rotarix®

ACTIVE COMPARATOR

Biological: Rotarix

Interventions

TV P2-VP8 BIOLOGICAL

90 µg of the TV P2-VP8 vaccine IM plus oral placebo administered on study days 1, 29 and 57

TV P2-VP8

Rotarix BIOLOGICAL

Rotarix® PO plus IM placebo administered on study days 1, 29 and 57

Rotarix®

Eligibility Criteria

• Age: 6 Weeks - 8 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• PATH: lead
• Bill and Melinda Gates Foundation: collaborator
• SK Bioscience Co., Ltd.: collaborator

Study Sites (1)

Centre for Infectious Disease Research in Zambia (CIDRZ)

Lusaka, Zambia

RECRUITING

Related Publications (1)

• Tewari T, Armah G, Cunliffe NA, Chisenga CC, Witte D, Kukula V, Jere KC, Simuyandi M, Damanka S, Mwinjiwa E, Kazimbaya K, Atuguba F, Williams J, Chilengi R, Csedrik J, Gast C, Fix A, Cryz S. Safety, immunogenicity, and relative efficacy of a parenteral trivalent rotavirus subunit vaccine candidate (TV P2-VP8) in healthy Ghanaian, Malawian, and Zambian infants. Vaccine. 2026 Jan 5;70:128019. doi: 10.1016/j.vaccine.2025.128019. Epub 2025 Nov 29.

  PMID: 41319434 DERIVED

MeSH Terms

Interventions

RIX4414 vaccine

Study Officials

• George Armah, PhD

  Noguchi Memorial Institute for Medical Research, University of Ghana, Legon

  PRINCIPAL INVESTIGATOR

• Desiree Witte, MD

  Malawi-Liverpool-Wellcome Trust (MLW) Clinical Research Programme

  PRINCIPAL INVESTIGATOR

• Roma Chilengi, MD

  Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joanne Csedrik, RN, MPH

CONTACT

+1-202-540-4496; jcsedrik@path.org

Tushar Tewari, MD

CONTACT

+91-11-40640005; ttewari@path.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 3, 2019
• First Posted: July 8, 2019
• Study Start: October 10, 2019
• Primary Completion: December 15, 2025
• Study Completion: December 15, 2025
• Last Updated: April 9, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Within 12 months of completion of study
• Access Criteria: Researchers who provide a methodologically sound proposal may be provided access after Sponsor permission.

Locations

ZA (1)