NCT03527173

A Study to Evaluate the Efficacy, Safety and Immunogenicity of a Vaccine Designed to Protect Against Infection With Shigella Sonnei in Healthy Adults

Efficacy, Safety and Immunogenicity of GVGH Shigella Sonnei Vaccine (1790GAHB) in a Human Challenge Study of Healthy Non-immune Adults

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 71 (actual)
• Sponsor: GlaxoSmithKline · Industry
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

The purpose of this study is to evaluate the efficacy, safety and immunogenicity of the GSK3536852A vaccine, which was designed to protect against shigellosis caused by Shigella sonnei (S. sonnei) and is using the new Generalized Modules for Membrane Antigens (GMMA) platform technology developed by GlaxoSmithKline (GSK) Vaccines Institute for Global Health (GVGH). The study vaccine could be the stepping stone for the development of a multivalent broadly protective Shigella vaccine for vaccination of impoverished communities where shigellosis is endemic. However, a standalone monovalent vaccine against S. sonnei could be used to protect travelers against diarrheal shigellosis, as the vast majority of travelers' shigellosis is caused by S. sonnei, and even to protect infants in endemic regions where shigellosis is primarily caused by S. sonnei. The GSK3536852A vaccine has been tested in two Phase I dose escalation studies in Europe to assess its safety and immunogenicity via three routes of administration: intramuscular (IM), intranasal (IN) and intradermal (ID). The results from the first study (dose escalation with IM vaccination) have shown that the vaccine has an acceptable safety profile and is well-tolerated up to a dose of 100 micrograms (µg). The results from the second study (dose escalation with ID, IN and IM vaccination) showed that GSK3536852A vaccine is well-tolerated also when administered by the ID and IN routes of vaccination. However, immunogenicity data have shown that GSK3536852A vaccine administered by the ID and IN routes is not as immunogenic as GSK3536852A vaccine administered by the IM route. Therefore, it has been decided to proceed with the clinical development program of this vaccine only using the IM vaccination route. In terms of dosage, the regimen tested in Phase I studies (three doses given one month apart) did not show any significant benefit from the third dose in terms of immunogenicity, therefore a two dose schedule was selected for next studies. A Phase IIa study, conducted in endemic regions of Africa (i.e., Kenya), has been completed and confirmed the acceptable safety profile and immunogenicity of GSK3536852A vaccine. Performing this vaccine-human challenge study may give the opportunity to establish evidence of clinical protection induced by the candidate S. sonnei vaccine (GSK3536852A vaccine) at an early development stage.

Detailed description

The original study protocol has been amended due to requests from the Food and Drug Administration (FDA), requests from the funder of the study, Bill \& Melinda Gates Foundation (BMGF), to add an additional interim analysis for immunogenicity data that will accelerate the release of key results to help the planning of other studies, and to further align the protocol to other GSK studies and to the challenge model established at the Cincinnati Children's Hospital Medical Centre.

Conditions

• Dysentery, Bacillary

Interventions

Type	Name	Description
BIOLOGICAL	S.sonnei vaccine	Subjects receiving 2 doses of the study vaccine by intramuscular route, 28 days apart (at Day 1 and Day 29).
DRUG	Placebo	Subjects receiving 2 doses of placebo by intramuscular route, 28 days apart (at Day 1 and Day 29).
BIOLOGICAL	S. sonnei 53G challenge strain	Subjects receiving the challenge dose of S. sonnei 53G strain, orally, at Day 57.

Timeline

• Start date: 2018-08-29
• Primary completion: 2019-05-08
• Completion: 2019-11-11
• First posted: 2018-05-17
• Last updated: 2020-07-28
• Results posted: 2020-05-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study