Understanding Typhoid Disease After Vaccination

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Brief Title

Understanding Typhoid Disease After Vaccination

Official Title

Understanding Typhoid Disease After Vaccination: a Single Centre, Randomised, Doubleblind, Placebo Controlled Study to Evaluate M01ZH09 in a Healthy Adult Challenge Model, Using Ty21a Vaccine as a Positive Control.

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.
    

Detailed Description

      Typhoid is a serious infection killing up to 600,000 people every year; it is a frequent
      cause of fever and hospital admission in areas where disease is common. As the infection is
      restricted to humans, it should be possible to eliminate typhoid; better vaccines and ways of
      confirming infection are required in order for this to succeed. We propose to use a recently
      established human typhoid challenge model in order to evaluate a novel oral vaccine candidate
      and to develop new methods for diagnosing typhoid.

      Although there are vaccines available to prevent typhoid, they offer little protection to
      populations where typhoid predominates, especially young children. Currently, the
      effectiveness of vaccines against typhoid cannot be predicted, as measures of protection
      against typhoid are unknown. As a result, implementation of vaccine programmes in disease
      endemic regions currently requires large and expensive trials in each new population,
      significantly delaying programmatic implementation.

      We will use a typhoid challenge model to achieve our goal of accelerating the introduction of
      more effective vaccines into populations with a high burden of disease. Healthy adults will
      be vaccinated with either a novel oral typhoid vaccine or vaccine-placebo prior to being
      infected with the bacteria causing typhoid. This will allow us to measure the effectiveness
      of the vaccine and to identify components of the immune response important in producing
      protection against infection.

      Current methods for confirming typhoid infection are slow and insensitive, particularly in
      endemic regions where the cost of laboratory equipment is prohibitive. In this project, we
      will also explore ways to diagnose typhoid, with the aim of developing tests that are quick,
      reliable and are be cost-effective in resource-poor settings. This would improve individual
      patient management, and allow accurate measurement of disease burden, which is vital to
      improve the efforts of vaccine programmes.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Diagnosis of typhoid fever


Condition

Typhoid Fever

Intervention

Vaccine placebo (excipients only)

Study Arms / Comparison Groups

 M01ZH09 vaccine
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

99

Start Date

October 7, 2011

Completion Date

August 31, 2021

Primary Completion Date

December 2015

Eligibility Criteria

        Inclusion criteria:

          -  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.

        Exclusion Criteria:

          -  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.

          -  Hypersensitivity to any component of the vaccine or are hypersensitive to two or more
             of the following antibiotics: ciprofloxacin, azithromycin, ampicillin, trimethoprim
             sulfamethoxazole.

          -  Female participant who is pregnant, lactating or who is unwilling to ensure that they
             or their partner use effective contraception one month prior to vaccination and
             continue to do so until two negative stool samples obtained a week apart, a minimum of
             1 week after completion of antibiotic treatment have been obtained.

          -  Current occupation involving: clinical or social work with direct contact with young
             children (defined as those attending pre-school groups, nursery or aged less than 2
             years); highly susceptible patients or persons in whom typhoid infection would have
             particularly serious consequences (i.e. those who are immunocompromised or
             debilitated); care work involving the elderly.

          -  Current occupation as a commercial food handler involving the preparation or serving
             of unwrapped foods not subjected to further heating.

          -  Household contact with a young child (defined as above).

          -  Household/close contact who is immunocompromised.

          -  Scheduled elective surgery or other procedures requiring general anaesthesia during
             the vaccine/challenge period, at time of enrolment.

          -  Participants who have taken part in other research involving an investigational
             product (IMP) within the 30 days prior to enrolment.

          -  Have received blood, blood products and/or plasma derivatives including parenteral
             immunoglobulin preparations in the previous 3 months

          -  Any other significant disease or disorder which, in the opinion of the investigator,
             may put the participants at risk because of participation in the study, may influence
             the result of the study, or affect the participant's ability to participate in the
             study.
      

Gender

All

Ages

18 Years - 60 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Andrew J Pollard, , 

Location Countries

United Kingdom

Location Countries

United Kingdom

Administrative Informations


NCT ID

NCT01405521

Organization ID

OVG 2011/02

Secondary IDs

2011-000381-35

Responsible Party

Sponsor

Study Sponsor

University of Oxford

Collaborators

 Wellcome Trust

Study Sponsor

Andrew J Pollard, Principal Investigator, Oxford Vaccine Group, Department of Paediatrics, University of Oxford


Verification Date

December 2020