NCT01405521

Brief Summary

Using an established model of human typhoid infection, whereby healthy adults are deliberately infected with typhoid-causing bacteria, the investigators will determine how effective a new oral typhoid vaccine (M01ZH09) is in preventing infection. A previously licensed oral typhoid vaccine (Ty21a) will be used to make sure the challenge model used works properly.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
99

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Oct 2011

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 28, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 29, 2011

Completed
2 months until next milestone

Study Start

First participant enrolled

October 7, 2011

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2015

Completed
6.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 6, 2022

Completed
Last Updated

May 6, 2023

Status Verified

December 1, 2020

Enrollment Period

4.2 years

First QC Date

July 28, 2011

Last Update Submit

May 3, 2023

Conditions

Typhoid FeverEnteric FeverTyphoid

Keywords

typhoid vaccine M01ZH09Ty21a typhoid vaccine

Outcome Measures

Primary Outcomes (1)

  • Diagnosis of typhoid fever

    Typhoid fever defined as development of Gram negative bacteraemia after day 5 or temperature over 38C persisting for 12 hours or more. Typhoid challenge defined as ingestion of virulent S. Typhi (Quailes strain).

    2 weeks after typhoid challenge

Study Arms (3)

M01ZH09 vaccine

EXPERIMENTAL
Biological: M10ZH09 vaccine

Vaccine placebo

PLACEBO COMPARATOR
Biological: Vaccine placebo (excipients only)

Ty21a vaccine

OTHER

Positive control

Biological: Ty21a

Interventions

Vaccine placebo (excipients only)BIOLOGICAL

single oral dose,

Vaccine placebo
Ty21aBIOLOGICAL

3 oral doses, alternate days

Also known as: Vivotif
Ty21a vaccine
M10ZH09 vaccineBIOLOGICAL

single oral dose

Also known as: Typhella
M01ZH09 vaccine

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Male or female aged 18 - 60 years inclusive and in good health.
  • Have an abdominal ultrasound scan result documented demonstrating no evidence of gallbladder pathology.
  • Willing to allow their general practitioner and/or hospital consultant (if relevant) and the Health Protection Unit to be notified of participation in the study.
  • Agree to refrain from blood donation in the future if diagnosed with typhoid fever.
  • Be willing to have 24-hour contact with study staff during the four weeks post-challenge.

You may not qualify if:

  • Have previously received any typhoid vaccine, been resident in a typhoid endemic country for over 6 months, been diagnosed with probable or confirmed typhoid infection or been challenged with Salmonella Typhi or enrolled in a typhoid challenge study.
  • Have any known or suspected impairment or alteration of immune function.
  • History of significant cardiovascular disease.
  • History of significant respiratory disease.
  • History of significant endocrine disorder.
  • History of significant renal or bladder disease.
  • History of biliary tract disease.
  • History of significant gastrointestinal disease.
  • History of significant neurological disease.
  • History of significant metabolic disease.
  • History of significant haematological diagnosis.
  • History of psychiatric illness requiring hospitalisation, current known or suspected drug or alcohol misuse.
  • History of significant infectious disease.
  • History of non-benign cancer.
  • Presence of any implants or prostheses.
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine

Oxford, United Kingdom

Location

Related Publications (8)

  • Gibani MM, Voysey M, Jin C, Jones C, Thomaides-Brears H, Jones E, Baker P, Morgan M, Simmons A, Gordon MA, Cerundolo V, Pitzer VE, Angus B, Levine MM, Darton TC, Pollard AJ. The Impact of Vaccination and Prior Exposure on Stool Shedding of Salmonella Typhi and Salmonella Paratyphi in 6 Controlled Human Infection Studies. Clin Infect Dis. 2019 Apr 8;68(8):1265-1273. doi: 10.1093/cid/ciy670.

    PMID: 30252031BACKGROUND

  • Darton TC, Blohmke CJ, Giannoulatou E, Waddington CS, Jones C, Sturges P, Webster C, Drakesmith H, Pollard AJ, Armitage AE. Rapidly Escalating Hepcidin and Associated Serum Iron Starvation Are Features of the Acute Response to Typhoid Infection in Humans. PLoS Negl Trop Dis. 2015 Sep 22;9(9):e0004029. doi: 10.1371/journal.pntd.0004029. eCollection 2015 Sep.

    PMID: 26394303BACKGROUND

  • Juel HB, Thomaides-Brears HB, Darton TC, Jones C, Jones E, Shrestha S, Sie R, Eustace A, Galal U, Kurupati P, Van TT, Thieu NTV, Baker S, Blohmke CJ, Pollard AJ. Salmonella Typhi Bactericidal Antibodies Reduce Disease Severity but Do Not Protect against Typhoid Fever in a Controlled Human Infection Model. Front Immunol. 2018 Jan 17;8:1916. doi: 10.3389/fimmu.2017.01916. eCollection 2017.

    PMID: 29387052BACKGROUND

  • Blohmke CJ, Hill J, Darton TC, Carvalho-Burger M, Eustace A, Jones C, Schreiber F, Goodier MR, Dougan G, Nakaya HI, Pollard AJ. Induction of Cell Cycle and NK Cell Responses by Live-Attenuated Oral Vaccines against Typhoid Fever. Front Immunol. 2017 Oct 12;8:1276. doi: 10.3389/fimmu.2017.01276. eCollection 2017.

    PMID: 29075261BACKGROUND

  • Barton A, Hill J, Bibi S, Chen L, Jones C, Jones E, Camara S, Shrestha S, Jin C, Gibani MM, Dobinson H, Waddington C, Darton TC, Blohmke CJ, Pollard AJ. Genetic Susceptibility to Enteric Fever in Experimentally Challenged Human Volunteers. Infect Immun. 2022 Apr 21;90(4):e0038921. doi: 10.1128/iai.00389-21. Epub 2022 Mar 7.

    PMID: 35254093BACKGROUND

  • Darton TC, Baker S, Randall A, Dongol S, Karkey A, Voysey M, Carter MJ, Jones C, Trappl K, Pablo J, Hung C, Teng A, Shandling A, Le T, Walker C, Molina D, Andrews J, Arjyal A, Basnyat B, Pollard AJ, Blohmke CJ. Identification of Novel Serodiagnostic Signatures of Typhoid Fever Using a Salmonella Proteome Array. Front Microbiol. 2017 Sep 19;8:1794. doi: 10.3389/fmicb.2017.01794. eCollection 2017.

    PMID: 28970824BACKGROUND

  • Darton TC, Jones C, Dongol S, Voysey M, Blohmke CJ, Shrestha R, Karkey A, Shakya M, Arjyal A, Waddington CS, Gibani M, Carter MJ, Basnyat B, Baker S, Pollard AJ. Assessment and Translation of the Antibody-in-Lymphocyte Supernatant (ALS) Assay to Improve the Diagnosis of Enteric Fever in Two Controlled Human Infection Models and an Endemic Area of Nepal. Front Microbiol. 2017 Oct 23;8:2031. doi: 10.3389/fmicb.2017.02031. eCollection 2017.

    PMID: 29109704BACKGROUND

  • Darton TC, Jones C, Blohmke CJ, Waddington CS, Zhou L, Peters A, Haworth K, Sie R, Green CA, Jeppesen CA, Moore M, Thompson BA, John T, Kingsley RA, Yu LM, Voysey M, Hindle Z, Lockhart S, Sztein MB, Dougan G, Angus B, Levine MM, Pollard AJ. Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a. PLoS Negl Trop Dis. 2016 Aug 17;10(8):e0004926. doi: 10.1371/journal.pntd.0004926. eCollection 2016 Aug.

    PMID: 27533046RESULT

Related Links

MeSH Terms

Conditions

Typhoid Fever

Interventions

Ty21a typhoid vaccine

Condition Hierarchy (Ancestors)

Salmonella InfectionsEnterobacteriaceae InfectionsGram-Negative Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Study Officials

  • Andrew J Pollard

    Oxford Vaccine Group, Department of Paediatrics, University of Oxford

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 28, 2011

First Posted

July 29, 2011

Study Start

October 7, 2011

Primary Completion

December 1, 2015

Study Completion

May 6, 2022

Last Updated

May 6, 2023

Record last verified: 2020-12

Locations

GB(1)