Human Challenge Model With ST-only Enterotoxigenic Escherichia Coli

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02870751
• Date of registration: 13/08/2016
• Prospective Registration: No
• Primary sponsor: University of Bergen
• Public title: Human Challenge Model With ST-only Enterotoxigenic Escherichia Coli ETECvacWP2
• Scientific title: Developing A Human Challenge Model For Evaluating Vaccines Against ST-producing Enterotoxigenic Escherichia Coli
• Date of first enrolment: May 2016
• Target sample size: 30
• Recruitment status: Unknown status
• URL: https://clinicaltrials.gov/show/NCT02870751
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Prevention. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Norway

Contacts

• Name: Kurt Hanevik, MD, PhD

• Name: Halvor Sommerfelt, MD, PhD
• Affiliation: Centre for International Health, University of Bergen

• Name: Kurt Hanevik, MD, PhD

Key inclusion & exclusion criteria

Inclusion Criteria:

- Provide written informed consent before initiation of any study procedures.

- Healthy as judged by the Principal Investigator (PI) and determined by medical
history, physical examination, and medication history.

- Within 15 days of vaccination, have normal screening laboratories for white blood
cells (WBC), hemoglobin (Hgb), platelets, absolute neutrophil count (ANC), sodium,
potassium, chloride, bicarbonate, blood urea nitrogen (BUN), creatinine, alanine
aminotransferase (ALT), C-reactive protein (CRP).

- Demonstrate comprehension of the protocol procedures and knowledge of study by passing
a written examination (passing grade is at least 80 percent).

- Capable of understanding, consenting and complying with the entire study protocol.

- Female subjects must be of non-childbearing potential, (as defined as surgically
sterile or postmenopausal for more than 1 year), or if of childbearing potential must
be practicing abstinence or using an effective licensed method of birth control (e.g.,
history of hysterectomy or tubal ligation; use hormonal or barrier birth control such
as implants, injectables, combined oral contraceptives, some intrauterine devices
(IUDs), cervical sponges, diaphragms, condoms with spermicidal agents, or must have a
vasectomized partner) within 2 months of infection and must agree to continue such
precautions during the study and for 30 days after the Day 56 study visit. Male
subjects must agree not to father a child for 90 days after the Day 28 study visit. A
woman is eligible if she is monogamous with a vasectomized male.

- Agrees not to participate in another clinical trial during the study period.

Exclusion Criteria:

- Women who are pregnant or lactating or have a positive serum pregnancy test at
screening or positive urine pregnancy test upon admission to inpatient facility.

- Abnormal Vital signs, defined as:

- Hypertension (systolic blood pressure >140 mm Hg or diastolic blood pressure >90
mm Hg) at rest on 2 separate days; or (heart rate <55 at rest on 2 separate days)

- Respiratory rate >17

- Temperature >/= 38.0 C (100.4 F) or symptoms of an acute self-limited illness
such as an upper respiratory infection or gastroenteritis within 7 days of
inoculum.

- Active positive Hepatitis B, C, and Human Immunodeficiency Virus (HIV) serologies.

- History of antimicrobial treatment in the 2 weeks before bacterial inoculum

- Received previous experimental E. coli, LT, or cholera vaccines or live E. coli or
Vibrio cholerae challenges; or previous infection with cholera or diarrheagenic E.
coli.

- Abnormal bowel habits as defined by fewer than 3 stools per week or more than 2 stools
per day in the past 6 months.

- History of chronic gastrointestinal illness, including severe dyspepsia (mild or
moderate heartburn or epigastric pain occurring no more than 3 times per week is
permitted), lactose intolerance, or other significant gastrointestinal tract disease.

- Regular use (weekly or more often) of laxatives, anti-diarrheal, anti-constipation, or
antacid therapy.

- History of major gastrointestinal surgery, excluding uncomplicated appendectomy or
cholecystectomy.

- Long-term use of oral steroids, parenteral steroids, or high-dose inhaled steroids
(>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6
months (Nasal and topical steroids are allowed).

- Have a diagnosis of schizophrenia or other major psychiatric diagnosis.

- Receiving the following psychiatric drugs: aripiprazole, clozapine, ziprasidone,
haloperidol, molindone, loxapine, thioridazine, molindone, thiothixene, pimozide,
fluphenazine, risperidone, mesoridazine, quetiapine, trifluoperazine, chlorprothixene,
chlorpromazine, perphenazine, trifluopromazine, olanzapine, carbamazepine, divalproex
sodium, lithium carbonate or lithium citrate

- History of receiving immunoglobulin or other blood product within the 3 months before
enrollment in this study.

- Traveled to Enterotoxigenic Escherichia coli (ETEC) endemic areas within the past 2
years, ever having used Cholera/ETEC vaccine (Dukoral) or having been raised in a
cholera or ETEC endemic area.

- Received any licensed vaccine within 2 weeks (for inactivated vaccines) or 4 weeks
(for live vaccines) before enrollment in this study.

- An acute or chronic medical condition that, in the opinion of the investigator, would
render ETEC infection unsafe or would interfere with the evaluation of responses. This
includes, but is not limited to: known or suspected immunodeficiency, known chronic
liver disease, significant renal disease, unstable or progressive neurological
disorders, history of diabetes, cancer (other than a healed skin lesion), heart
disease (in the hospital for a heart attack, history of irregular heart beat or
fainting caused by an irregular heart beat), unconsciousness (other than a single
brief "concussion"), seizures (other than with fever when subject was a child <5 years
old), asthma requiring treatment with inhaler or medication in the prior 2 years,
autoimmune disease or eating disorder, and transplant recipients.

- Received an experimental agent (vaccine, drug, biologic, device, blood product or
medication) within 1 month before enrollment in this study or expects to receive an
experimental agent during the study.

- History of alcohol or drug abuse in the last 5 years.

- Planned to travel abroad in the time between vaccination and 30 days following the
ETEC inoculum dose.

- Any condition that would, in the opinion of the Site Investigator, place the subject
at an unacceptable risk of injury or render the subject unable to meet the
requirements of the protocol.

- Use of prescription and over-the-counter (OTC) medications that contain acetaminophen,
aspirin, ibuprofen, and other nonsteroidal anti-inflammatory drugs within 48 hours
prior to receiving the investigational product.

- Use of prescription acid suppression medication or OTC antacids within 72 hours of
investigational product administration.

- Subjects with autoimmune disorders, chronic inflammatory disorders or neurological
disorders with a potential autoimmune correlation.



Age minimum: 18 Years
Age maximum: 45 Years
Gender: All

Health Condition(s) or Problem(s) studied

Diarrhea, Infantile

Intervention(s)

Biological: TW11681 or TW10722

Primary Outcome(s)

Diarrheal disease [Time Frame: 5 days]

Adverse event monitoring [Time Frame: 30 days]

Secondary Outcome(s)

Immune responses towards challenge strain [Time Frame: 2 years]

Secondary ID(s)

NRC234364

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

University of Maryland, College Park

Haukeland University Hospital