Immunogenicity, Safety and Tolerability of the Typhoid Fever Vaccine Candidate M01ZH09 in Healthy Adults
Condition: Typhoid
MeSH terms: Typhoid Fever
Intervention: Dose of 5.0 x 10^9 CFU (Cohort 1); Dose of 7.5 x 10^9 CFU (Cohort 2); Dose of 1.1 x 10^10 CFU (Cohort 3); Dose of of 1.7 x 10^10 CFU (Cohort 4); Placebo (Cohorts 1-4 pooled)
Intervention description: S. typhi (Ty2 aroC-ssaV-) ZH9 live attenuated typhoid vaccine, single dose, oral administration; S. typhi (Ty2 aroC-ssaV-) ZH9 live attenuated typhoid vaccine, single dose, oral administration; S. typhi (Ty2 aroC-ssaV-) ZH9 live attenuated typhoid vaccine, single dose, oral administration; S. typhi (Ty2 aroC-ssaV-) ZH9 live attenuated typhoid vaccine, single dose, oral administration; Excipients only, single dose, oral administration
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 187.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This study is to investigate the safety, tolerability and immunogenicity of the typhoid fever
      vaccine candidate M01ZH09 manufactured at commercial scale, at a new manufacturing facility.
      The vaccine will be delivered as a single oral dose to healthy, typhoid vaccine-naïve adults.
    

Eligibility criteria:

        Inclusion Criteria:

          -  healthy adult subjects aged 18 to 50 years inclusive, who are able and willing to give
             informed consent, following a detailed explanation of participation in protocol

          -  available for the duration of the study and available for scheduled and potential
             additional visits

        Exclusion Criteria:

          -  women who are pregnant, breast-feeding or of childbearing potential and unwilling to
             use a reliable method of contraception throughout the study period

          -  history of anaphylactic shock following vaccination by any route have phenylketonuria

          -  hypersensitivity to any component of the vaccine or are hypersensitive to two of the
             following antibiotics: ciprofloxacin, azithromycin, ampicillin, trimethoprim
             sulfamethoxazole

          -  received antibiotic medication within 14 days prior to dosing

          -  received any vaccine within 4 weeks prior to dosing or plan to receive a vaccine
             within 4 weeks after dosing

          -  received any vaccine against Salmonella typhi (licensed or investigational) or ever
             suffered from typhoid fever

          -  subjects who test positive for hepatitis B, hepatitis C, HIV or human leucocyte
             antigen B-27

          -  known or suspected history of liver or active gall bladder disease, ongoing
             gastro-intestinal disease or abnormality

          -  commercial food handlers or health care workers with direct contact with high risk
             patients or who have household contacts with immuno-compromised individuals, pregnant
             women or children less than 2 years of age

          -  subjects who have a clinically significant amount of protein or haemoglobin in their
             urine or abnormality of their haematology or serum biochemistry parameters

          -  impairment of immune function or those receiving or have received cytotoxic drugs in
             the 6 months prior to study entry

          -  subjects who use antacids, proton pump inhibitors or H2 blockers on a regular basis or
             have consumed proton pump inhibitors or H2 blockers within 24 hours prior to dosing

          -  acute infections (including fever of 37.5 degrees Celsius or greater) on the day of
             dosing.

          -  subjects with chronic disease (e.g Crohn's disease, inflammatory bowel disease,
             diabetes) who cannot withstand a 3 hour fast

          -  substance abuse or a history of substance abuse that might interfere with
             participation in the study

          -  body mass index (BMI) is less than 19 or greater than 34 kg per m2

          -  clinically significant medical condition that precludes participation in the study

          -  subjects who have participated in an interventional clinical trial within 60 days of
             dosing