ShigETEC Vaccine Study in Bangladesh

Healthy Volunteers Clinical Trial

Official title: Early Clinical Development of a Live, Attenuated Combination Vaccine Against Shigella and ETEC Diarrhoea: Phase 1b Clinical Trial of ShigETEC Vaccine in Bangladeshi Adults and Three Paediatric Age Groups

Status Not yet recruiting

Clinical Trial Summary

The goal of this clinical trial is to test ShigETEC vaccine, a combination vaccine against Shigella and ETEC diarrhoea in Bangladeshi adults (aged 18-45 years) and paediatric participants of three different age groups (aged 2-5 years, 12-23 months and 6-11 months).

The main question[s] it aims to answer are:

• Safety and clinical tolerability of the vaccine

• Immune responses generated by the vaccine In the age-descending dose-escalating study

• Adult participants will be divided into 2 escalating dose cohorts

• Each age group of paediatric participants will be divided into 3 escalating dose cohorts

• Participants in each cohort will receive three doses of vaccine/placebo two weeks apart

• Solicited and unsolicited adverse events (AE) and serious adverse events (SAE) will be monitored after each vaccination dose

• Stool samples will be collected for immunological analysis and shedding of vaccine strain

• Blood samples will be collected for immunological analysis

Clinical Trial Description

A double-blind, randomized, placebo-controlled, age-descending and dose-escalating phase 1b clinical trial will be carried out in Bangladeshi adults and three paediatric age groups to evaluate the safety, clinical tolerance, and immunogenicity of ShigETEC, a live, attenuated Shigella/ETEC combination vaccine.

Objectives of the study

Primary Objectives:

To evaluate the safety and clinical tolerability of oral ShigETEC vaccine in Bangladeshi adults and different age groups of paediatric participants by monitoring the occurrence and severity of clinical signs and symptoms after administration of each of the three vaccinations.

Secondary Objectives:

• To evaluate the immune response to Shigella and ETEC (Enterotoxigenic Escherichia coli) antigens in blood and stool following administration of ShigETEC vaccine.

• To assess the fecal shedding of ShigETEC following ingestion.

The age-descending study will start testing the vaccine in healthy adults (aged 18-45 years) and move subsequently into three different paediatric age groups (aged 2-5 years, 12-23 months and 6-11 months). In the adult participants (group A), thirty-six participants will be enrolled and divided into 2 escalating dose cohorts. Each cohort of 18 healthy adults (12 vaccinees and 6 placebo recipients) will be randomized to receive three times vaccine/placebo two weeks apart. The first adult cohort (cohort A1) will receive the optimal vaccine dose (OVD) found in Phase I Europe trial (5x10^10 CFU). Cohort A2 will be given 4-fold higher dose than cohort A1 (2x10^11 CFU).

In each of the 2-5 years (group B), 12-23 months (group C), and 6-11 months age group (group D), 48 participants will be enrolled and divided into 3 escalating dose cohorts with 16 participants in each cohort (12 vaccinees and 4 placebo recipients). B1 cohort will be immunized with 25-fold lower than the OVD in EU (Europe) Phase 1 trial (2x10^9CFU). Cohorts B2 and B3 will be given higher doses in 5-fold increments, and thus cohort B2 will receive 1x10^10 CFU and cohort B3 will receive the OVD in EU Phase 1 trial (5x10^10 CFU). Cohort C1 will be vaccinated with 25-fold lower than the OVD in group B. Cohorts C2 and C3 will receive higher doses in 5-fold increments. Cohort D1 will be given 25- fold lower than the OVD in group C. Cohorts D2 and D3 will receive higher doses in 5-fold increments.

Recruitment, screening, and consenting of the participants will take place at the urban field site of icddr,b in Mirpur. In each cohort, the first dose and immediate safety evaluation will be conducted at the Clinical Trial Unit (CTU), an inpatient facility, where the participants will be closely monitored for 24 hours post-vaccination. If the initial dose is deemed safe, all participants will return to the CTU to receive the second and third time vaccine or placebo on an outpatient basis. Follow-up visits will take place 7 days after each dosing and 28 days after last dosing at the Mirpur field office.

Primary safety endpoint:

1. Solicited reactogenicity

2. Unsolicited adverse event (AE)

3. Serious adverse event (SAE)

Secondary immunogenicity endpoints:

1. Changes of antibody responses to antigens from baseline to each visit after vaccination:

• Antibody responses IgG (Immunglobulin G) and IgA (Immunglobulin A) in all age groups in serum

• IgA in lymphocyte supernatant (ALS) and fecal extract

2. Functional antibodies:

• ETEC toxins neutralization titers

• Serum bactericidal activity

• Inhibition of bacterial adherence and entry to human colon epithelial cells

3. Antibody responses to Shigella and ETEC proteins and peptides

4. Antibody avidity against LT, ST and selected Shigella antigens

Secondary shedding endpoint:

Intestinal replication of the ShigETEC vaccine ;

Related Conditions & MeSH terms

• Healthy Volunteers

• NCT number: NCT05987488
• Study type: Interventional
• Source: Eveliqure Biotechnologies GmbH
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: September 2023
• Completion date: September 2025