Development of a Live Attenuated Rotavirus Vaccine as a Human Infection Challenge Model

NCT04123119 | Completed

• 1 other identifier: HicVac Rota
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diarrhoeal Disease

Outcome Measures

Primary Outcomes (1)

• Measurement of serum RV-IgA and RV-IgG

  Four (4) fold change in Serum anti-rotavirus specific IgA titles at 3 months post dose two

  3 months

Secondary Outcomes (2)

• Assessment of Viral shedding in stool

  5 months

• Measurement of cytokines

  5 months

Study Arms (1)

Rotarix Arm

EXPERIMENTAL

Biological: Rotavirus vaccine

Interventions

Rotavirus vaccine BIOLOGICAL

An exploratory and observational cohort study following infants receiving two standard doses of live, attenuated, oral Rotarix™ administered at 6 \& 10 weeks.

Rotarix Arm

Eligibility Criteria

• Age: 6 Weeks - 8 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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 since birth or planned administration during the study period
• History of chronic administration (defined as more than 14 days) of immunosuppressant medications, including corticosteroids.
• 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.

Sponsors & Collaborators

• Centre for Infectious Disease Research in Zambia: lead
• Imperial College London: collaborator
• Christian Medical College, Vellore, India: collaborator

Study Sites (1)

George Clinical Research Site

Lusaka, 10101, Zambia

Location

MeSH Terms

Interventions

Rotavirus Vaccines

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Roma Chilengi, MBCHB

  Centre for Infectious Disease Research in Zambia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2019
• First Posted: October 10, 2019
• Study Start: January 22, 2019
• Primary Completion: May 10, 2019
• Study Completion: May 10, 2019
• Last Updated: October 14, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)