A Study to Evaluate the Efficacy, Safety and Immunogenicity of a Vaccine Designed to Protect Against Infection With Shigella Sonnei in Healthy Adults
Condition: Dysentery, Bacillary
MeSH terms: Dysentery, Bacillary; Dysentery
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): S.sonnei vaccine; Placebo; S. sonnei 53G challenge strain
Intervention type(s): Biological; Drug; Biological
Intervention description(s): Subjects receiving 2 doses of the study vaccine by intramuscular route, 28 days apart (at Day 1 and Day 29).; Subjects receiving 2 doses of placebo by intramuscular route, 28 days apart (at Day 1 and Day 29).; Subjects receiving the challenge dose of S. sonnei 53G strain, orally, at Day 57.
Other intervention name(s): GSK3536852A vaccine; GAHB-Placebo
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Challenge; Efficacy; Shigellosis; Vaccination