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DiarrheaPhase 2NCT04658914

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

A Phase 2 study testing Rotarix and Trivalent P2-VP8 in people with Diarrhea and Diarrhea Rotavirus, run by Centre for Infectious Disease Research in Zambia at 1 site in Zambia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 6 to 10 weeksHealthy volunteers can take part
Conditions the study is for
Diarrhea, Diarrhea Rotavirus
What is being tested?
Rotarix and Trivalent P2-VP8
Could I receive a placebo?
No, everyone receives an active treatment
How many people
720 participants
Where
1 siteZambia
Study dates
15 Apr 2021to 30 Jan 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 to 10 weeks
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Zambia1 site

  • Chawama first level hospital

    Lusaka, Lusaka Province, 10101

Other trials in Zambia

About this study

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.

Read the detailed description

This is a randomized, open-label clinical trial of Rotarix and trivalent VP8 subunit vaccine given alone or in combined schedules to 720 infants in Zambia at 6, 10 and 14 weeks followed by challenge at 18 weeks used to assess mucosal immunity.

Potential participants will be identified through antenatal and child health monitoring clinics in selected facilities in Lusaka Zambia. Interested parents will be invited to the clinical research site for informed consent procedures and assessment of eligibility. Children meeting the eligibility criteria with written informed consent for participation will be randomized to one of the four available study arms using simple randomization in block sizes of 8. Blood, stool, and saliva samples will be collected prior to completing vaccination according to randomization arm. All parents/guardians will be provided with post immunisation diary cards to document any reactions following vaccination. Trained study staff will contact parents and guardians of enrolled participants weekly to enquire on the child's health and assist with documentation of solicited reactions following vaccinations.

Enrolled children will be followed up for at least five months following enrollment. Follow up vaccinations will be provided each month until all children have completed all assigned study vaccinations. Upon completion of study vaccination, participants will be challenged with oral rotavirus vaccine, Rotarix TM to assess mucosal immunity.

Primary outcome:

The primary objective of the study will be 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. The primary outcomes will be prevalence of rotavirus (Rotarix) shedding at any timepoint in samples collected 5,7 and 9 days after challenge.

Secondary outcomes:

i.) Seroconversion following vaccination: Detection of an increase in seroconversion in either of the combined vaccination arms compared with Rotarix alone.

ii.) Immune boosting. We will compare the number of gut-homing (alpha 4 beta 7+) Immunoglobulin A (IgA) and Immunoglobulin G (IgG) rotavirus VP8-specific Antibody secreting cells (ASCs) 7 days after the third clinic visit in 50 infants from each study arm (i.e. after the first VP8 vaccine booster dose, after the third VP8 vaccine dose (alone or in combination with Rotarix), or after no vaccine (control) in the Rotarix only arm).

Being tested
Rotarix, Trivalent P2-VP8
Keywords
Human Infection Challenge
Medical subject headings
Diarrhea

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RotarixBiological

    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.

  • Trivalent P2-VP8Biological

    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.

Study groups in NCT04658914
Study groupRoleWhat they receive
rotarix onlyNo interventionRotarix 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 onlyExperimentalParenteral 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.
Receives: Biological: Trivalent P2-VP8
Rotarix + 1 dose P2-VP8ExperimentalRotarix 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.
Receives: Biological: Rotarix; Biological: Trivalent P2-VP8
Rotarix + 3 doses P2-VP8ExperimentalRotarix 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.
Receives: Biological: Rotarix; Biological: Trivalent P2-VP8

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 5-9 days after Challenge

Secondary outcomes (2)

  1. Seroconversion following vaccination

    Seroconversion After 2 doses of Rotarix in Zambia seroconversion was 60% (130/216) in an earlier study and 45% (10/22) in our Medical Research Council UK MRC-funded pilot of Rotarix challenge, based on IgA to whole virus cell culture lysate (largely anti -VP6 antibodies). Seroconversion based on anti-VP8 antibodies has not been studied after Rotarix administration but may be similar.

    Measured: 14 and 18 weeks of age

  2. Immune boosting

    i.) We will compare the number of gut-homing (alpha 4 beta 7+) IgA and IgG rotavirus VP8-specific ASCs 7 days after the third clinic visit in 50 infants from each study arm (i.e. after the first VP8 vaccine booster dose, after the third VP8 vaccine dose (alone or in combination with Rotarix), or after no vaccine (control) in the Rotarix only arm).

    Measured: 7 days after 3rd clinic visit

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2020
  2. Study start15 Apr 2021
  3. Primary completion30 Aug 2022
  4. Study completion30 Jan 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
single centre open label study, randomized, controlled trial
Masking
None (open label)
Enrolment
720 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04658914
Sponsor's protocol ID
MRC Rotavirus HIC
Status last verified
May 2025
First submitted
18 Nov 2020
Last updated
15 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Communicate with the participants results of the study and plans to share de-identified data. Disseminate to internal research meetings as well as the Ministry of Health Zambia. Submit manuscripts, publications, in peer review journal and also present at local and international scientific conferences

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Rotarix and Trivalent P2-VP8 in people with Diarrhea and Diarrhea Rotavirus, run by Centre for Infectious Disease Research in Zambia at 1 site in Zambia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Zambia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Vaccine Shedding (time frame: 5-9 days after Challenge). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04658914.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2025.

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