Immunogenicity, Safety and Tolerability of the Typhoid Fever Vaccine Candidate M01ZH09 in Healthy Adults

Emergent BioSolutions

Status and phase: Completed; Phase 2

Conditions: Typhoid

Treatments: Biological: Dose of 5.0 x 10^9 CFU (Cohort 1); Biological: Dose of 1.1 x 10^10 CFU (Cohort 3); Biological: Dose of of 1.7 x 10^10 CFU (Cohort 4); Biological: Dose of 7.5 x 10^9 CFU (Cohort 2); Other: Placebo (Cohorts 1-4 pooled)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00679172

MS01.13

Details and patient eligibility

About

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.

Full description

This was a randomised, double-blind, placebo-controlled, single dose, dose escalation study with 4 dosing cohorts. Within each cohort, 45 evaluable subjects were planned (36 subjects receiving M01ZH09, 9 receiving placebo).

Enrollment: 187 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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187 participants in 4 patient groups

M01ZH09 Vaccine Candidate Cohort 1

Experimental group

Description:

Dose of 5.0 x 10\^9 colony forming units (CFU) S. typhi (Ty2 aroC-ssaV-) ZH9 or placebo, administered as a single, oral dose

Treatment:

Biological: Dose of 5.0 x 10^9 CFU (Cohort 1)

Other: Placebo (Cohorts 1-4 pooled)

M01ZH09 Vaccine Candidate Cohort 2

Experimental group

Description:

Dose of 7.5 x 10\^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9 or placebo, administered as a single, oral dose

Treatment:

Other: Placebo (Cohorts 1-4 pooled)

Biological: Dose of 7.5 x 10^9 CFU (Cohort 2)

M01ZH09 Vaccine Candidate Cohort 3

Experimental group

Description:

Dose of 1.1 x 10\^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9 or placebo, administered as a single, oral dose

Treatment:

Other: Placebo (Cohorts 1-4 pooled)

Biological: Dose of 1.1 x 10^10 CFU (Cohort 3)

M01ZH09 Vaccine Candidate Cohort 4

Experimental group

Description:

Dose of of 1.7 x 10\^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9 or placebo, administered as a single, oral dose

Treatment:

Other: Placebo (Cohorts 1-4 pooled)

Biological: Dose of of 1.7 x 10^10 CFU (Cohort 4)