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

NCT ID: NCT00679172

Last Updated: 2024-04-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 187 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2008-12-31

Brief 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.

Detailed 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).

Conditions

Typhoid

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

M01ZH09 Vaccine Candidate Cohort 1

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

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

S. typhi (Ty2 aroC-ssaV-) ZH9 live attenuated typhoid vaccine, single dose, oral administration

Placebo (Cohorts 1-4 pooled)

Intervention Type: OTHER

Excipients only, single dose, oral administration

M01ZH09 Vaccine Candidate Cohort 2

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

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

S. typhi (Ty2 aroC-ssaV-) ZH9 live attenuated typhoid vaccine, single dose, oral administration

Placebo (Cohorts 1-4 pooled)

Intervention Type: OTHER

Excipients only, single dose, oral administration

M01ZH09 Vaccine Candidate Cohort 3

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

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

S. typhi (Ty2 aroC-ssaV-) ZH9 live attenuated typhoid vaccine, single dose, oral administration

Placebo (Cohorts 1-4 pooled)

Intervention Type: OTHER

Excipients only, single dose, oral administration

M01ZH09 Vaccine Candidate Cohort 4

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

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

S. typhi (Ty2 aroC-ssaV-) ZH9 live attenuated typhoid vaccine, single dose, oral administration

Placebo (Cohorts 1-4 pooled)

Intervention Type: OTHER

Excipients only, single dose, oral administration

Interventions

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

S. typhi (Ty2 aroC-ssaV-) ZH9 live attenuated typhoid vaccine, single dose, oral administration

Intervention Type: BIOLOGICAL

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

S. typhi (Ty2 aroC-ssaV-) ZH9 live attenuated typhoid vaccine, single dose, oral administration

Intervention Type: BIOLOGICAL

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

S. typhi (Ty2 aroC-ssaV-) ZH9 live attenuated typhoid vaccine, single dose, oral administration

Intervention Type: BIOLOGICAL

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

S. typhi (Ty2 aroC-ssaV-) ZH9 live attenuated typhoid vaccine, single dose, oral administration

Intervention Type: BIOLOGICAL

Placebo (Cohorts 1-4 pooled)

Excipients only, single dose, oral administration

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Emergent BioSolutions

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen Lockhart, DM

Role: STUDY_DIRECTOR

Emergent BioSolutions

Locations

Miami Research Associates

South Miami, Florida, United States

John Hopkins Bloomberg School of Public Health

Baltimore, Maryland, United States

Unit of Infectious Diseases, University of Vermont College of Medicine

Burlington, Vermont, United States

Countries

United States

References

Lyon CE, Sadigh KS, Carmolli MP, Harro C, Sheldon E, Lindow JC, Larsson CJ, Martinez T, Feller A, Ventrone CH, Sack DA, DeNearing B, Fingar A, Pierce K, Dill EA, Schwartz HI, Beardsworth EE, Kilonzo B, May JP, Lam W, Upton A, Budhram R, Kirkpatrick BD. In a randomized, double-blinded, placebo-controlled trial, the single oral dose typhoid vaccine, M01ZH09, is safe and immunogenic at doses up to 1.7 x 10(10) colony-forming units. Vaccine. 2010 Apr 30;28(20):3602-8. doi: 10.1016/j.vaccine.2010.02.017. Epub 2010 Feb 24.

Reference Type: RESULT

PMID: 20188175 (View on PubMed)

Other Identifiers

MS01.13

Identifier Type: -

Identifier Source: org_study_id