Contact information
Type
Scientific
Primary contact
Prof Jeremy Farrar
ORCID ID
Contact details
The Hospital for Tropical Diseases
Oxford University Clinical Research Unit
190 Ben Ham Tu
Ho Chi Minh City
District 5
Viet Nam
+84 (0)8 923 7954
jfarrar@oucru.org
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
075596
Study information
Scientific title
Acronym
MS01.08
Study hypothesis
The purpose of the study is to determine the safety and immunogenicity of the oral vaccine M01ZH09 in healthy, paediatric, Asian subjects prior to initiating field trials in an endemic area.
Ethics approval
The trial has received full ethical approval from the OXTREC committee (ref: 021-06) and the local Institutional Review Board (The Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam). The approval dates are 25th July 2006, for conditional approval, and final unconditional approval was received on the 18th October 2006.
Study design
Randomised, placebo-controlled, single-blind, single dose study.
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Prevention
Patient information sheet
Condition
Typhoid fever prophylaxis
Intervention
Subjects deemed eligible after screening will be randomised to receive an oral dose of either active vaccine or matching placebo.
Safety will be monitored by:
1. Diary recordings of body temperature
2. Assessment of Adverse Events (AEs)
3. Vital signs
4. Stool samples for microbiological analyses
5. Urine dipstick tests
6. Immunogenicity will be assessed in all subjects using an Enzyme-Linked ImmunoSorbent Assay (ELISA) method for serum Immunoglobulin G (IgG) and serum Immunoglobulin A (IgA) in all subjects. Enzyme-Linked Immunosorbent SPOT (ELISPOT) tests will be conducted on samples from subjects aged 11 to 14 years of age.
Intervention type
Drug
Phase
Not Specified
Drug names
M01ZH09 typhoid vaccine (oral live S. typhi [Ty2 aroC- ssaV-] ZH9)
Primary outcome measures
The proportion of subjects reporting Serious Adverse Events (SAEs) attributed to the study medication.
Secondary outcome measures
Safety - the proportion of subjects:
1. Experiencing an elevated body temperature, of 38.5°C or greater, in the 14 days following dosing, attributed to study medication
2. Demonstrating persistent faecal shedding of the vaccine strain
3. Withdrawn from the study due to adverse events, including bacteraemia, attributed to study medication
4. With clinically significant changes in laboratory parameters, from day zero to any time post dosing, which are attributed to study medication
Immunogenicity:
1. Develop a positive immune response to S. typhi LipoPolySaccharide (LPS) as assessed by an increase in S. typhi LPS specific IgG
2. Develop a positive immune response to S. typhi LPS as assessed by an increase S.typhi LPS specific IgA
3. At day seven, have more than or equal to 4 Antibody-Secreting Cells (ASCs) per 10^6 Peripheral Blood Mononuclear Cells (PBMC), secreting IgA specific for S. typhi LPS detected by ELISPOT assay (subjects over ten years of age)
Overall trial start date
26/01/2007
Overall trial end date
31/05/2007
Reason abandoned
Eligibility
Participant inclusion criteria
1. Healthy paediatric subjects aged five to 14 years
2. Are able and willing to take part in the trial
3. Parents or guardians give written permission for their childs participation, following a detailed explanation of the study
Participant type
Patient
Age group
Child
Gender
Not Specified
Target number of participants
150
Participant exclusion criteria
1. Any clinically significant medical or psychiatric condition or abnormal laboratory results on screening, which preclude participation in the study
2. A body weight under 17 kg (five to ten year olds), or under 27 kg (11 to 14 year olds)
3. A confirmed pregnancy, or are breast feeding
4. A known hypersensitivity to two or more of the following antibiotics: ciprofloxacin, azithromycin or trimethoprim-sulfamethoxazole, or have used antibiotics/antibacterials within 14 days prior to administration of study medication
5. A known hypersensitivity to any component of the vaccine or bicarbonate solution, phenylketonuria or those who have experienced anaphylactic shock after any vaccination
6. Received Vivotif, in the last ten years or any other vaccine against S. typhi, in the last five years, or who have ever suffered from typhoid fever
7. Direct contact with patients in special care units or immuno-compromised individuals, a positive bacterial culture of their faecal sample, obtained at the screening visit, for any Salmonella species, a known impairment of immune function or family members who are Human Immunodeficiency Virus (HIV) positive
8. A significant acute febrile illness at time of dosing chronic diseases, a current problem of substance abuse or who are currently or recently involved in a clinical study
Recruitment start date
26/01/2007
Recruitment end date
31/05/2007
Locations
Countries of recruitment
Viet Nam
Trial participating centre
The Hospital for Tropical Diseases
Ho Chi Minh City
District 5
Viet Nam
Sponsor information
Organisation
Emergent Product Development UK Ltd (UK)
Sponsor details
545 Eskdale Road
Winnersh Triangle
Wokingham
RG41 5TU
United Kingdom
+44 (0)118 944 3300
clindev@ebsi.com
Sponsor type
Industry
Website
Funders
Funder type
Charity
Funder name
The Wellcome Trust (UK) (grant ref: 075596)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
1. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20668668
Publication citations
-
Results
Tran TH, Nguyen TD, Nguyen TT, Ninh TT, Tran NB, Nguyen VM, Tran TT, Cao TT, Pham VM, Nguyen TC, Tran TD, Pham VT, To SD, Campbell JI, Stockwell E, Schultsz C, Simmons CP, Glover C, Lam W, Marques F, May JP, Upton A, Budhram R, Dougan G, Farrar J, Nguyen VV, Dolecek C, A randomised trial evaluating the safety and immunogenicity of the novel single oral dose typhoid vaccine M01ZH09 in healthy Vietnamese children., PLoS ONE, 2010, 5, 7, e11778, doi: 10.1371/journal.pone.0011778.