Contact information
Type
Scientific
Primary contact
Dr Ann-Mari Svennerholm
ORCID ID
Contact details
Dept. of microbiology and immunology
University of Gothenburg
Box 435
Gothenburg
40530
Sweden
+46 (0)31 786 6202
ann-mari.svennerholm@microbio.gu.se
Additional identifiers
EudraCT number
2009-015741-23
ClinicalTrials.gov number
Protocol/serial number
EudraCT number: 2009-015741-23, OEV-120
Study information
Scientific title
Evaluation of the safety and immunogenicity of a prototype enterotoxigenic Escherichia coli (ETEC) vaccine: a three-armed, double-blinded, randomised, single-centre study
Acronym
Study hypothesis
Enterotoxigenic E. coli (ETEC) bacteria are known to be a primary cause of traveller's diarrhoea and diarrhoea in children in developing countries. ETEC bacteria produce heat-labile toxin (LT), heat stable toxin (ST) or both toxins and colonise the intestine by means of so called colonisation factors (CFs).
The aim of this study is to determine if a new potentially improved prototype ETEC vaccine, consisting of bacteria over-expressing the colonisation factor CFA/I and administered together with a hybrid of the binding subunits of LT and cholera toxin (LTB/CTB), is safe and gives rise to stronger immune responses than a previously tested ETEC vaccine, consisting of a natural CFA/I expressing ETEC strain + CTB.
Ethics approval
1. Independent Ethics Committee in the Gothenburg region (IECGR) in Sweden approved on 26/10/2009, amendment approved 13/03/2010, ref no 570-09
2. Western Institutional Review Board (WIRB) Olympia, Washington, USA approved on 11/05/2010, ref no 20100565
Study design
Three-armed double-blinded randomised single-centre study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Enterotoxigenic E. coli (ETEC) diarrhoea
Intervention
Healthy adult volunteers will be immunised with two consecutive doses of two different ETEC vaccines (Vaccine A and Vaccine B) with 12-16 days interval. Vaccine A consists of ETEC bacteria that over-express the colonisation factor CFA/I + LTB/CTB hybrid protein. Vaccine B consists of a previously tested CFA/I expressing ETEC strain + CTB protein. The vaccines will be mixed with a bicarbonate buffer and administered orally.
The volunteers will be randomised into three different study arms:
First arm: Subjects immunised with 2 doses of Vaccine A
Second arm: Subject immunised with 2 doses of Vaccine B
Third arm: Subjects immunised with 2 doses of Vaccine B; each dose containing 4 times higher numbers of bacteria and 4 times more LTB/CTB protein compared to the second arm
Intervention type
Drug
Phase
Not Applicable
Drug names
Enterotoxigenic E. coli (ETEC) vaccine
Primary outcome measure
1. To evaluate the safety of a new prototype ETEC vaccine (Vaccine A) and to compare the immunogenicity, i.e. intestinal or intestine-derived IgA antibody responses, against CFA/I and LTB, of the new prototype ETEC vaccine with that of a previously tested ETEC strain in combination with CTB (Vaccine B)
1.1. The safety of the vaccines will be determined by evaluation of study diaries throughout the study period, by clinical chemistry and haematology tests (at screening and 7 days after each immunisation) and by physical examination (at screening and on day 42)
1.2. Intestinal antibody responses are based on enzyme-linked immunosorbent assay (ELISA) measurements of specific antibodies in stool extracts (day 0, 7 and 21)
1.3. Intestine-derived antibody responses are based on ELISA measurements of specific antibodies secreted from cultured peripheral blood cells (using the ALS method) or on ELISPOT assay determinations of the numbers of specific antibody secreting cells (ASC) among peripheral blood mononuclear cells (day 0, 7 and 21)
Secondary outcome measures
1. To evaluate IgA and IgG antibody responses against CFA/I, LTB and CTB in serum as well as specific IgA in those mucosal samples that are not used as primary endpoints
1.1. Serum and intestinal antibody responses are based on enzyme-linked immunosorbent assay (ELISA) measurements of specific antibodies in sera (day 0, 7, 14, 21 and 42) and stool (day 0, 7 and 21), respectively
1.2. Intestine-derived antibody responses are based on ELISA measurements of specific antibodies secreted from cultured peripheral blood cells (using the ALS method) or on enzyme-linked immunosorbent spot (ELISPOT) assay determinations of the numbers of specific antibody secreting cells (ASC) among peripheral blood mononuclear cells
Overall trial start date
12/05/2010
Overall trial end date
01/06/2011
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Males or females aged 18-55 years
2. Healthy constitution as established by medical history, medical examination and clinical chemistry and haematology testing
3. Give written informed consent to participate
4. Willing and able to communicate with the investigators and understand the requirements of the study
5. Sexually active females should unless being menopausal agree to use reliable contraception as assessed by the investigator, during 1 month prior to inclusion and one month after the last intake of study vaccine and should have a negative pregnancy test before each vaccination
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
60
Participant exclusion criteria
1. Has received the oral cholera vaccine Dukoral® in the last 5 years
2. Travelled to ETEC-endemic area within the last 2 years
3. Concomitant intake of immunomodulating drugs during the study period or less than four weeks prior to the first immunisation
4. Vaccination with some other vaccine during the study period or within two weeks prior to trial vaccination
5. Any condition which would limit the subjects ability to complete the study in the opinion of the investigator
6. History of drug or chemical abuse in the year before the study
7. Receipt of any other investigational product in the month before study entry
8. Concomitant participation in any other clinical study
9. Donation of blood 6 weeks before study entry or at any time during the study
10. Females who are pregnant
11. Females who are nursing
12. History of gastrointestinal or systemic inflammatory or autoimmune disease
13. Any known hypersensitivity to any ingredient in the vaccines
14. Gastroenteritis within two weeks prior to vaccination
15. Antibiotic therapy within six weeks prior to the vaccination
Recruitment start date
12/05/2010
Recruitment end date
01/06/2011
Locations
Countries of recruitment
Sweden
Trial participating centre
Dept. of microbiology and immunology
Gothenburg
40530
Sweden
Sponsor information
Organisation
Gothenburg University Vaccine Research Institute (GUVAX) (Sweden)
Sponsor details
Dept. of microbiology and immunology
University of Gothenburg
Box 435
Gothenburg
40530
Sweden
+46 (0)31 786 6201
jan.holmgren@microbio.gu.se
Sponsor type
University/education
Website
Funders
Funder type
Other
Funder name
PATH (USA)
Alternative name(s)
Program for Appropriate Technology in Health
Funding Body Type
private sector organisation
Funding Body Subtype
Other non-profit
Location
United States of America
Funder name
Sahlgrenska University Hospital (Sweden) (ref: LUA/ALF)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Swedish Research Council (Sweden)
Alternative name(s)
Swedish Research Council, VR, SRC
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
Sweden
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
Basic results (scientific)
Publication list