Development of a Live Attenuated Rotavirus Vaccine as a Human Infection Challenge Model (NCT04123119) | Clinical Trial Compass
CompletedNot Applicable
Development of a Live Attenuated Rotavirus Vaccine as a Human Infection Challenge Model
Zambia22 participantsStarted 2019-01-22
Plain-language summary
The impact of licensed rotavirus vaccines in LMICs is limited by their lower immunogenicity and efficacy in these settings. Improved vaccines and vaccination schedules would result in substantially greater reductions in infant diarrhoeal disease and mortality. Placebo-controlled trials of new rotavirus vaccines are no longer ethical, leading to challenges for traditional routes of licensure for vaccines that are in the development pipeline.
A HIC model of rotavirus would address these challenges, whilst also offering an opportunity to study the causes of poor oral vaccine immunogenicity. Rotarix™ is in routine use in Zambia administered at 6 and 10 weeks infant age. Shedding of rotavirus vaccine after vaccination has recently been explored as a measure of mucosal immunity, analogous to oral poliovirus vaccine challenge models.
We propose to explore methodological development of an attenuated vaccine as a HIC model to advance rotavirus immunology and vaccinology in Zambian infants. We will evaluate use of minimally invasive procedures including sublingual/submandibular sampling and stool collection for viral shedding as measures of vaccine-induced and naturally acquired mucosal immunity. This approach holds the potential to develop the first rotavirus HIC model in a low-income country and could be used to accelerate licensure of new rotavirus vaccines and explore causes of poor oral vaccine efficacy as well as correlates of vaccine protection.
To do this, we will recruit a cohort of 22 Zambian infants receiving Rotarix™ at 6 and 10 weeks as part of their routine immunisation. Infants will be followed up actively on the day of vaccination, days 1,3,5 and 7 following each vaccine dose for collection of stool and saliva samples. Blood samples for IgA and IgG titres will be collected on days 0, 28, 31 and 56, and standard ELISA methods used to determine vaccine seroconversion.
The work brings together collaborators at the Centre for Infectious Disease Research in Zambia, Imperial College in UK and Christian Medical College, Vellore in India to prepare the Zambian centre as a potential HIC model site.
Who can participate
Age range
6 Weeks – 8 Weeks
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion Criteria:
* healthy infants as established by medical history and clinical examination before entering study
* age: \> 6 and \<8 weeks at the time of enrollment
* parental ability and willingness to provide informed consent
* parental intention to remain in the area with the child during the study period.
Exclusion Criteria:
* Presence of fever on the day of enrollment
* Acute disease at the time of enrollment
* Concurrent participation in another clinical trial throughout the entire timeframe for this study
* Presence of malnutrition 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)
* History of congenital abdominal disorders, intussusception, or abdominal surgery
* Known or suspected impairment of immunological function based on medical history and physical examination
* Prior receipt of rotavirus vaccine
* A known sensitivity or allergy to any components of the study vaccine
* History of anaphylactic reaction
* Major congenital or genetic defect
* Participant's parents not able, available or willing to accept active follow-up by the study staff
* Has received any immunoglobulin therapy and/or blood products sinc…
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Measurement of serum RV-IgA and RV-IgG
Timeframe: 3 months
Trial details
NCT IDNCT04123119
SponsorCentre for Infectious Disease Research in Zambia