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

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

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 Overview

• Status: Recruiting
• Conditions: Rotavirus Infection of Children
• Intervention / Treatment: Biological: TV P2-VP8; Biological: Rotarix

• Study Type: Interventional
• Enrollment (Anticipated): 8200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Joanne Csedrik, RN, MPH; Phone Number: +1-202-540-4496; Email: jcsedrik@path.org
• Study Contact Backup: Name: Tushar Tewari, MD; Phone Number: +91-11-40640005; Email: ttewari@path.org

Study Locations

• Zambia
  • Lusaka, Zambia
    • Recruiting
    • Centre for Infectious Disease Research in Zambia (CIDRZ)
    • Contact: Roma Chilengi, MD
    • Contact: Caroline Chisenga, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 month (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: PATH
• Collaborators: Bill and Melinda Gates Foundation; SK Bioscience Co., Ltd.
• Investigators: Principal Investigator: 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

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2019
• Primary Completion (Anticipated): December 15, 2025
• Study Completion (Anticipated): December 15, 2025

Study Registration Dates

• First Submitted: July 3, 2019
• First Submitted That Met QC Criteria: July 3, 2019
• First Posted (Actual): July 8, 2019

Study Record Updates

• Last Update Posted (Actual): April 9, 2021
• Last Update Submitted That Met QC Criteria: April 8, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Gastrointestinal Diseases; Reoviridae Infections; Gastroenteritis; Rotavirus Infections
• Other Study ID Numbers: CVIA 061

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Summary results for primary and secondary objectives
• IPD Sharing Time Frame: Within 12 months of completion of study
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal may be provided access after Sponsor permission.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No