NCT02531802

Enterotoxigenic Escherichia Coli (ETEC) ETVAX Vaccine Trial in Bangladesh

A Randomized, Double-blind, Placebo-controlled, Dose-Escalation Study Evaluating the Safety, Tolerability, and Immunogenicity of an Oral Inactivated ETEC Vaccine (ETVAX) Alone and Together With dmLT Adjuvant in Descending Age Groups in Bangladesh

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 475 (actual)
• Sponsor: PATH · Academic / Other
• Sex: All
• Age: 6 Months – 45 Years
• Healthy volunteers: Accepted

Summary

The purpose of this study is to determine if the ETEC vaccine ETVAX with and without dmLT adjuvant is safe and immunogenic in adults, children, toddlers and infants in Bangladesh.

Detailed description

This Phase I/II trial will serve to assess whether ETVAX is safe and provides mucosal as well as systemic immune responses against the key protective antigens when tested in different age-groups in Bangladesh. This study provides an opportunity to test the safety profile of a mucosal adjuvant, double-mutant LT (dmLT), in adults and children, as well as provide the opportunity to potentially assess the ability of dmLT to further enhance the mucosal and systemic antibody responses to key antigens in the ETVAX vaccine among age groups in developing country sites, like Bangladesh, that have proved refractory to oral immunization with enteric vaccines. In addition, this study also allows for the evaluation of the potential dose-sparing effect of dmLT when combined with a lower dose of vaccine. Finally, this clinical trial is considered an essential study along the critical path of the overall clinical development plan before determining whether the vaccine can be tested for protective efficacy in children in developing countries.

Conditions

• Escherichia Coli Diarrhea

Interventions

Type	Name	Description
BIOLOGICAL	ETVAX	Varying dosages of liquid ETVAX vaccine (Batch BX1003574). A full dose consisted of: * Hybrid protein between the B-subunit of the E. coli heat-labile enterotoxin and the B-subunit of the cholera toxin (LCTBA): 1 mg * E. coli ETEX 21 formalin inactivated: 1.3 mg colonization factor 1 (CFA/I) * E. coli ETEX 22 formalin inactivated: 6.4 mg coli surface antigen 3 (CS3) * E. coli ETEX 23 formalin inactivated: 1.1 mg coli surface antigen 5 (CS5) * E. coli ETEX 24 phenol inactivated: 0.5 mg coli surface antigen 6 (CS6) The vaccine was given together with sodium bicarbonate effervescent granules (Recip), which was dissolved in water and mixed with the vaccine suspension prior to oral administration. The buffer was used to prevent degradation of LCTBA hybrid protein by the gastric acid.
BIOLOGICAL	dmLT	Varying dosages of dmLT, a derivative of wild-type enterotoxigenic Escherichia coli LT that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine. These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.
OTHER	Bicarbonate Buffer	Sodium bicarbonate buffer dissolved in 150 ml of potable water

Timeline

• Start date: 2015-10-01
• Primary completion: 2017-07-29
• Completion: 2017-07-29
• First posted: 2015-08-24
• Last updated: 2018-09-12
• Results posted: 2018-09-12

Locations

1 site across 1 country: Bangladesh