Safety Study of Live Attenuated Oral Shigella (WRSS1) Vaccine in Bangladeshi Adults and Children
Condition: Diarrhea
MeSH terms: Diarrhea
Study type: Interventional

Summary: 
      This is a research study about an experimental (investigational) oral Shigella sonnei -
      Walter Reed S. sonnei (WRSS1). WRSS1 is a live vaccine that is being made to prevent disease
      from Shigella, which causes bloody, watery diarrhea. Infants and children living in
      developing countries experience the greatest consequences of this disease. The purpose of
      this study is to find a dose of the vaccine that is safe, tolerable, and develops an immune
      response. About 39 healthy adults, ages 18-39, and 48 healthy children, ages 5-9, will
      participate in this study. Once the vaccine is proven safe and tolerable in adults, then it
      will be tested in the children. This study will require volunteers to stay in the research
      facility for several nights for the first dose; they will not be required to stay overnight
      for the second and third doses. Participants will be assigned to receive 1 of 3 vaccine dose
      levels by mouth. Study procedures include: stool samples, blood samples and documenting side
      effects. Participants will be involved in study related procedures for about 8 months.
    

Detailed description: 
      This is a single site, double-blind, randomized, placebo-controlled, dose-escalation,
      age-descending study that will start testing the vaccine in healthy adults and move
      subsequently into school-age children. The study is designed as 2 parts, each part comprising
      3 cohorts. The cohort receiving the lowest dose in Parts A and B will receive only one
      administration of vaccine or placebo; the subsequent two higher dose cohorts in Parts A and B
      will receive three administrations of vaccine or placebo. In each cohort, the first dose and
      immediate safety evaluation will be conducted at the International Centre for Diarrhoeal
      Disease Research (icddr,b) Inpatient Unit, where the participants will be admitted for
      observation for 72 hours. Follow-up visits for participants in A1 and B1 will take place on
      an outpatient basis at the Mirpur, Bangladesh (Mirpur) Field Office. Second and third
      vaccinations within A2, A3, B2, and B3 cohorts and all follow-up visits will take place on an
      outpatient basis at the Mirpur Field Office. Before enrolling participants in subsequent
      cohorts to receive a higher vaccine dose, or to move to the lower age group, the safety data
      from the previous cohort(s) (through Study Day 7) will be evaluated and reviewed by the
      Internal Protocol Safety Team (IPST) comprised of the study physician, the Medical Monitor
      from GVK Biosciences (GVK), the principal investigator, and the Medical Monitor from PATH
      Vaccine Solutions (PVS). Upon completion of the last adult cohort, the Data Safety Monitoring
      Board (DSMB -an advisory body to the Ethical Review Committee) will convene to review the
      cumulative safety data and IPST recommendation, and determine whether to proceed to Part B
      (children). Adverse events (AE)s will be graded according to standardized criteria. The
      immunogenicity outcome measures of interest include serum immunoglobulin G (IgG) and
      immunoglobulin A (IgA) antibodies by Antibodies in Lymphocyte Supernatant (ALS) assay against
      S. sonnei2a lipopolysaccharide (LPS), shedding profile of WRSS1, and vaccine-specific mucosal
      IgA responses.

      The proposed study builds upon successful preliminary observations with this vaccine in the
      US, Israel and Thailand. While secondary objectives include studying the immunogenicity of
      the WRSS1 vaccine, the primary goal of the current trial is to establish a clear safety
      profile for the WRSS1 vaccine in adults and children 5-9 years old.The primary objective of
      the study is to evaluate the safety and tolerability of the vaccine; the secondary objective
      is to evaluate vaccine immunogenicity.
    

Intervention name(s): WRSS1
Intervention type(s): Biological
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Shigellosis