Condition category
Infections and Infestations
Date applied
03/03/2011
Date assigned
18/03/2011
Last edited
18/03/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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 measures

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

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 subject’s 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)

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

Funding Body Type

government organisation

Funding Body Subtype

government non-federal

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes