Human Challenge With Live-attenuated Rotavirus to Assess Next-generation Rotavirus Vaccines in Africa

NCT04658914 | Completed Phase 2 DMC

• 1 other identifier: MRC Rotavirus HIC
• Study Type: interventional
• Target: 720
• Locations: 1 country
• Sites: 1

Brief Summary

Despite the widespread introduction of vaccines against Rotavirus, Rotavirus continues to be a cause of significant morbidity and mortality in the developing world. This study will assess protection against rotavirus infection and investigate immune correlates of protection following vaccination with a novel trivalent VP8 subunit rotavirus vaccine used alone or in combination with oral rotavirus vaccine.

Conditions

Diarrhea; Diarrhea Rotavirus

Keywords

Human Infection Challenge

Outcome Measures

Primary Outcomes (1)

• Vaccine Shedding

  to detect a reduction in the proportion of children shedding vaccine rotavirus in stool at any timepoint 5 -9 days after challenge, among children immunized with P2-VP8 subunit vaccine alone or in combination with Rotarix, compared with infants receiving Rotarix alone. We estimate that approximately 50% (range 30-70%) of children previously vaccinated with 2 doses of Rotarix will shed Rotarix detected by Polymerase Chain Reaction (PCR) at any timepoint 5-9 days after challenge

  5-9 days after Challenge

Secondary Outcomes (2)

• Seroconversion following vaccination

  14 and 18 weeks of age

• Immune boosting

  7 days after 3rd clinic visit

Study Arms (4)

rotarix only

NO INTERVENTION

Rotarix will be administered at 6 and 10 weeks of age following the national Expanded Program for Immunization (EPI) schedule. A challenge dose of Rotarix will be administered at 18 weeks of age and stool samples collected just before challenge and 5, 7 \& 9 days later.

P2 VP8 only

EXPERIMENTAL

Parenteral P2-VP8 subunit vaccine will be administered at 6, 10 and 14 weeks of age. A challenge dose of Rotarix will be administered at 18 weeks of age and stool samples collected just before challenge and 5, 7 \& 9 days later.

Biological: Trivalent P2-VP8

Rotarix + 1 dose P2-VP8

EXPERIMENTAL

Rotarix will be administered at 6 and 10 weeks of age, followed by parenteral P2-VP8 subunit vaccine at 14 weeks of age. A challenge dose of Rotarix will be administered at 18 weeks of age and stool samples collected just before challenge and 5, 7 \& 9 days later.

Biological: Rotarix; Biological: Trivalent P2-VP8

Rotarix + 3 doses P2-VP8

EXPERIMENTAL

Rotarix and parenteral P2-VP8 subunit vaccine will be coadministered at 6 and 10 weeks of age, with an additional dose of P2-VP8 subunit vaccine administered at 14 weeks of age. A challenge dose of Rotarix will be administered at 18 weeks of age and stool samples collected just before challenge and 5, 7 \& 9 days later.

Biological: Rotarix; Biological: Trivalent P2-VP8

Interventions

Rotarix BIOLOGICAL

Live-attenuated oral human rotavirus vaccine (Rotarix) manufactured by GlaxoSmithKline containing at least 10\^6 CCID50(median cell culture infective doses) of G1P\[8\] rotavirus, RIX4414 strain produced in Vero cells. This vaccine is an oral suspension with a single dose (1.5ml) administered using an oral applicator.

Rotarix + 1 dose P2-VP8; Rotarix + 3 doses P2-VP8

Trivalent P2-VP8 BIOLOGICAL

Trivalent P2-VP8 subunit vaccine manufactured by SK Chemicals containing 90ug of each VP8 antigen derived from P\[4\] (DS-1), P\[6\] (1076), and P\[8\] (Wa) rotavirus strains fused to the P2 epitope from tetanus toxoid and adsorbed to aluminium hydroxide. A single dose (0.5ml) of this vaccine is administered intramuscularly through injection.

P2 VP8 only; Rotarix + 1 dose P2-VP8; Rotarix + 3 doses P2-VP8

Eligibility Criteria

• Age: 6 Weeks - 10 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Healthy infants as established by medical history and physical examination.
• Infants will be 6-10 weeks old at time of enrollment
• parents plan to remain in the area for the duration of the study.
• Parent/guardian understands the study procedures and willing to provide informed consent to participate in the study

You may not qualify if:

• Acutely unwell
• Infant or infant's mother has syndromic or documented evidence of being immunocompromised (independent of HIV status)
• Known allergy to any vaccine component
• Previously received rotavirus vaccine
• Received immunosuppressive medication
• Major congenital or genetic abnormality
• Any condition in the parents/infant that, in the judgment of the investigator, would interfere with or serves as a contraindication to protocol adherence or a participant's parents' ability to give informed consent.
• Participant's parents not available or willing to accept active follow-up by the study staff

Sponsors & Collaborators

• Centre for Infectious Disease Research in Zambia: lead
• Medical Research Council: collaborator
• PATH: collaborator
• University of Liverpool: collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• Imperial College London: collaborator

Study Sites (1)

Chawama first level hospital

Lusaka, Lusaka Province, 10101, Zambia

Location

MeSH Terms

Conditions

Diarrhea

Interventions

RIX4414 vaccine

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Roma Chilengi, MD

  Centre for Infectious Disease Research in Zambia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: single centre open label study, randomized, controlled trial

Study Record Dates

• First Submitted: November 18, 2020
• First Posted: December 9, 2020
• Study Start: April 15, 2021
• Primary Completion: August 30, 2022
• Study Completion: January 30, 2023
• Last Updated: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: after study completion

Locations

ZA (1)