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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

Primary Purpose

Rotavirus Infection of Children

Status

Recruiting

Phase

Phase 3

Locations

Zambia

Study Type

Interventional

Intervention

TV P2-VP8

Rotarix

About this trial

This is an interventional prevention trial for Rotavirus Infection of Children

Eligibility Criteria

6 Weeks - 8 Weeks (Child)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Centre for Infectious Disease Research in Zambia (CIDRZ)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

TV P2-VP8

Rotarix®

Arm Description

Outcomes

Primary Outcome Measures

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)

Number of serious adverse events (SAEs), including intussusception

Number of Adverse Events (AEs) > or = to grade 2

Secondary Outcome Measures

Number of laboratory confirmed cases of very severe rotavirus gastroenteritis (VSRVGE; any strain)

VSRVGE is defined by a Vesikari score of >15

Number of P-type specific (P[4], P[6] and P[8]) laboratory confirmed cases of SRVGE and VSRGE

Number of laboratory confirmed cases of rotavirus gastroenteritis (any strain) of any severity

Number of laboratory confirmed cases hospitalized for RVGE (any severity)

Incidence of SRVGE and VSRVGE per 100 children-years

Full Information

NCT ID

NCT04010448

First Posted

July 3, 2019

Last Updated

April 8, 2021

Sponsor

PATH

Collaborators

Bill and Melinda Gates Foundation, SK Bioscience Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT04010448

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Recruiting

Study Start Date

October 10, 2019 (Actual)

Primary Completion Date

December 15, 2025 (Anticipated)

Study Completion Date

December 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

PATH

Collaborators

Bill and Melinda Gates Foundation, SK Bioscience Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rotavirus Infection of Children

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

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

ParticipantCare ProviderInvestigatorOutcomes 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.

Allocation

Randomized

Enrollment

8200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

TV P2-VP8

Arm Type

Experimental

Arm Title

Rotarix®

Arm Type

Active Comparator

Intervention Type

Biological

Intervention Name(s)

TV P2-VP8

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Rotarix

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of laboratory confirmed cases of severe rotavirus gastroenteritis (SRVGE; any strain)

Description

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

Title

Number of serious adverse events (SAEs), including intussusception

Time Frame

Through 28 days after the last dose of study vaccine

Title

Number of Adverse Events (AEs) > or = to grade 2

Time Frame

Through 28 days after the last dose of study vaccine

Secondary Outcome Measure Information:

Title

Number of laboratory confirmed cases of very severe rotavirus gastroenteritis (VSRVGE; any strain)

Description

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

Title

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

Title

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

Title

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

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Weeks

Maximum Age & Unit of Time

8 Weeks

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Joanne Csedrik, RN, MPH

Phone

+1-202-540-4496

jcsedrik@path.org

First Name & Middle Initial & Last Name or Official Title & Degree

Tushar Tewari, MD

Phone

+91-11-40640005

ttewari@path.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

George Armah, PhD

Organizational Affiliation

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

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Desiree Witte, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Roma Chilengi, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centre for Infectious Disease Research in Zambia (CIDRZ)

City

Lusaka

Country

Zambia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Roma Chilengi, MD

First Name & Middle Initial & Last Name & Degree

Caroline Chisenga, PhD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

Learn more about this trial

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

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