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
Intervention: S.sonnei vaccine; Placebo; S. sonnei 53G challenge strain
Intervention description: 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.
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Observer-blind The subject, the site and sponsor personnel involved in the clinical evaluation of the subjects are blinded while other study personnel may be aware of the treatment assignment.
Enrollment: 71.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Challenge; Efficacy; Shigellosis; Vaccination

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects who, in the opinion of the investigator, can and will comply with the
             requirements of the protocol.

          -  Written informed consent obtained from the subject prior to performing any study
             specific procedure.

          -  Individuals who, after the nature of the study has been explained to them, have shown
             adequate comprehension of the study procedures and knowledge of study.

          -  A male or female between, and including, 18 and 50 years of age at the time of the
             first vaccination.

          -  Healthy subjects as established by medical history and clinical examination before
             entering into the study.

          -  Seronegative for human immunodeficiency virus (HIV), hepatitis B and C.

          -  Female subjects of non-childbearing potential may be enrolled in the study.

          -  Female subjects of childbearing potential may be enrolled in the study, if the
             subject:

               -  Has practiced adequate contraception for 30 days prior to vaccination, and

               -  Has a negative pregnancy test on the day of vaccination, and

               -  Has agreed to continue adequate contraception during the entire study period.

        Exclusion Criteria:

          -  Received an investigational or non-registered medicinal product within 30 days prior
             to informed consent, or planned use during the study period.

          -  Any behavioral or cognitive impairment or psychiatric disease that, in the opinion of
             the investigator, may interfere with the subject's ability to participate in the
             study.

          -  History of any neurological disorders or seizures.

          -  Any other clinical condition that, in the opinion of the investigator, might pose
             additional risk to the subject due to participation in the study.

          -  Human Leukocyte Antigen (HLA)-B27 positive test at screening and/or with history of
             reactive arthritis.

          -  Clinical conditions representing a contraindication to intramuscular vaccination and
             blood draws.

          -  Chronic administration of immunosuppressants or other immune-modifying drugs during
             the period starting six months prior to the first vaccine/placebo dose. For
             corticosteroids, this will mean prednisone ≥ 20 milligrams (mg)/day, or equivalent.
             Inhaled except for doses > 800 µg/day and topical steroids are allowed.

          -  Administration of long-acting immune-modifying drugs at any time during the study
             period. Subjects may be on chronic or as needed medications if, in the opinion of the
             site principal investigator or appropriate sub-investigator, they pose no additional
             risk to subject safety or assessment of reactogenicity and immunogenicity and do not
             indicate a worsening of medical diagnosis or condition.

          -  Known bleeding diathesis or any condition that may be associated with a prolonged
             bleeding time.

          -  Concurrently participating in another clinical study, at any time during the study
             period, in which the subject has been or will be exposed to an investigational or a
             non-investigational vaccine/product.

          -  History of having participated in a previous Shigella challenge study.

          -  Individuals who have a previously laboratory confirmed case of disease caused by S.
             sonnei or serology positive for local anti S. sonnei LPS IgG Screening-ELISA at
             screening.

          -  History of any serious chronic or progressive disease according to judgment of the
             investigator.

          -  History of any malignancy or lymphoproliferative disorder.

          -  Known to be part of study personnel or being a close family member to the personnel
             conducting this study.

          -  History of anaphylactic reaction or allergy to vaccine/placebo or challenge agent
             components or any other allergies deemed by the investigator to increase the risk of
             an AE if they were to participate in the study.

          -  Known allergy to ciprofloxacin or the other antibiotics used for treatment as deemed
             by the investigator.

          -  Individuals receiving a course of antibiotics within a week of the challenge will be
             ineligible to receive the challenge strain.

          -  History of gastric acid hyper-secretory disorders as assessed and judged by the
             investigator or any other significant intestinal disorder.

          -  Any confirmed or suspected immunosuppressive or immunodeficient condition, based on
             medical history and physical examination.

          -  Family history of congenital or hereditary immunodeficiency.

          -  History of any reaction or hypersensitivity likely to be exacerbated by any component
             of the vaccine/placebo or challenge agent.

          -  Acute disease and/or fever at the time of enrolment.

          -  Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal
             functional abnormality, as determined by physical examination or laboratory screening
             tests. Chronic medical diagnoses or conditions should be stable for the last 60 days.
             This includes no change in chronic prescription medication, dose, or frequency as a
             result of deterioration of the chronic medical diagnosis or condition in the 60 days
             prior to enrolment.

          -  A clinically significant sign or symptoms of acute illness, significant anomalies in
             vital signs.

          -  Known to handle food as part of work related activities.

          -  Hepatomegaly, right upper quadrant abdominal pain or tenderness.

          -  Received immunoglobulins or any blood products within 180 days prior to informed
             consent or planned administration during the study period.

          -  Pregnant or lactating female.

          -  Female planning to become pregnant or planning to discontinue contraceptive
             precautions.

          -  Females with history of stillbirth, neonatal loss, or previous infant with anomaly,
             except those who have had a planned termination of pregnancy, hysterectomy or
             bilateral tubal ligation.

          -  History of chronic alcohol consumption and/or drug abuse. Chronic alcohol consumption
             is defined as: a prolonged period of frequent, heavy alcohol use; the inability to
             control drinking once it has begun; physical dependence manifested by withdrawal
             symptoms when the individual stops using alcohol; tolerance, or the need to use more
             and more alcohol to achieve the same effects; a variety of social and/or legal
             problems arising from alcohol use.

          -  Known to have close household or professional contacts with people with
             immunosuppressive condition.

          -  Documented HIV, hepatitis B and C positive subject.

          -  Any condition which, in the opinion of the investigator, may pose an increased and
             unreasonable safety risk to the subject if they participated in the study.

          -  Subjects with a baseline neutrophil count below 1800 cells per microliter (cells/µL)
             lower limit of normal range (LLN) OR with clinically significant abnormalities in
             other laboratory values, according to local reference ranges and investigator
             judgment.

          -  Previous history of Benign Ethnic Neutropenia, or drug related Neutropenia.

          -  Concomitant treatment with neutropenic agents.