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

NCT00679172 | Completed Phase 2 Results

• 1 other identifier: MS01.13
• Study Type: interventional
• Target: 187
• Locations: 1 country
• Sites: 3

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.

Conditions

Typhoid

Outcome Measures

Primary Outcomes (7)

• Number and Proportion of Subjects Reporting Suspected Unexpected Serious Adverse Reactions.

  Number and proportion of subjects reporting suspected unexpected serious adverse reactions (SUSARs).

  From start of dosing to 28 days post-dosing.

• Number and Proportion of Subjects Experiencing Symptomatic Fever.

  Number and proportion of subjects experiencing symptomatic (e.g., chills, rigors, sweating, headache, myalgia etc.) elevated body temperature of 38.0°C or more in the 14 days following dosing.

  From start of dosing to 14 days post-dosing.

• Number of Subjects Having Clinically Significant Changes in Laboratory Test Parameters.

  Number of subjects having clinically significant changes in clinical laboratory test parameters.

  From start of dosing to 28 days post-dosing.

• Number of Subjects Reporting Treatment-related TEAEs.

  Number of subjects having TEAEs considered by the principal investigator to be "possibly" or "probably" related to treatment.

  From start of dosing to 28 days post-dosing.

• Number and Proportion of Subjects Experiencing Bacteraemia.

  Number and proportion of subjects experiencing a proven bacteraemia attributed to the vaccine strain S. typhi (Ty2 aroC-ssaV-) ZH9.

  From start of dosing to 28 days post-dosing.

• Number of Subjects Having Shedding in Stool of Salmonella Typhi (S. Typhi) (Ty2 aroC-ssaV-) ZH9.

  Number of subjects having shedding in stool of S. typhi (Ty2 aroC-ssaV-) ZH9. Subjects were evaluated beyond Day 14 only in Cohort 4.

  Beyond 7 days post-dosing through 14 days post-dosing (Cohorts 1-3) or through 21 days post-dosing (Cohort 4).

• Number and Proportion of Subjects Developing an Immune Response as Determined by the Level of IgG and/or IgA Antibodies for S. Typhi Lipopolysaccharide (LPS).

  Number and proportion of subjects with increase of 70% (fold change of 1.7) in S. typhi LPS-specific serum IgG at Days 14 or 28 AND/OR increase of 50% (fold change of 1.5) in S. typhi LPS-specific serum IgA at Days 7 or 14. Serum IgG and IgA were assayed using enzyme-linked immunosorbent assay (ELISA).

  From baseline (pre-dose) to Days 14 or 28 (IgG) or to Days 7 or 14 (IgA).

Secondary Outcomes (6)

• Number and Proportion of Subjects Developing an Immune Response as Determined by the Level of IgA Antibodies for S. Typhi LPS.

  From baseline (pre-dose) to Days 7 or 14.

• Number and Proportion of Subjects Developing an Immune Response as Determined by the Level of IgG Antibodies for S. Typhi LPS.

  From baseline (pre-dose) to Days 14 or 28.

• Number and Proportion of Subjects Developing an Immune Response as Determined by the Level of IgG Antibodies for S. Typhi LPS.

  From baseline (pre-dose) to Days 7, 14, or 28.

• Number and Proportion of Subjects Developing an Immune Response at the Target Dose of 7.5 x 10^9 CFU (Cohort 2) as Determined by the Number of Antibody Secreting Cells (ASCs) Secreting IgA and/or Fold Change in IgG.

  At Day 7 (IgA); and from baseline (pre-dose) to Day 28 (IgG).

• Number and Proportion of Subjects Developing an Immune Response at the Target Dose of 7.5 x 10^9 CFU (Cohort 2) as Determined by the Number of ASCs Secreting IgA.

  Day 7.

Study Arms (4)

M01ZH09 Vaccine Candidate Cohort 1

EXPERIMENTAL

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

Biological: Dose of 5.0 x 10^9 CFU (Cohort 1); Other: Placebo (Cohorts 1-4 pooled)

M01ZH09 Vaccine Candidate Cohort 2

EXPERIMENTAL

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

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

M01ZH09 Vaccine Candidate Cohort 3

EXPERIMENTAL

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

Biological: Dose of 1.1 x 10^10 CFU (Cohort 3); Other: Placebo (Cohorts 1-4 pooled)

M01ZH09 Vaccine Candidate Cohort 4

EXPERIMENTAL

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

Biological: Dose of of 1.7 x 10^10 CFU (Cohort 4); Other: Placebo (Cohorts 1-4 pooled)

Interventions

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

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

M01ZH09 Vaccine Candidate Cohort 1

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

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

M01ZH09 Vaccine Candidate Cohort 2

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

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

M01ZH09 Vaccine Candidate Cohort 3

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

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

M01ZH09 Vaccine Candidate Cohort 4

Placebo (Cohorts 1-4 pooled) OTHER

Excipients only, single dose, oral administration

M01ZH09 Vaccine Candidate Cohort 1; M01ZH09 Vaccine Candidate Cohort 2; M01ZH09 Vaccine Candidate Cohort 3; M01ZH09 Vaccine Candidate Cohort 4

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emergent BioSolutions: lead

Study Sites (3)

Miami Research Associates

South Miami, Florida, 33143, United States

Location

John Hopkins Bloomberg School of Public Health

Baltimore, Maryland, 21205, United States

Location

Unit of Infectious Diseases, University of Vermont College of Medicine

Burlington, Vermont, 05405, United States

Location

Related Publications (1)

• 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.

  PMID: 20188175 RESULT

MeSH Terms

Conditions

Typhoid Fever

Condition Hierarchy (Ancestors)

Salmonella Infections; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Dr. Tim Babinchak
• Organization: Emergent Product Development Gaithersburg

(240) 631-3585

Study Officials

• Stephen Lockhart, DM

  Emergent BioSolutions

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2008
• First Posted: May 16, 2008
• Study Start: May 1, 2008
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: April 9, 2024
• Results First Posted: June 7, 2017

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)