Enterotoxigenic Escherichia (E.) coli (ETEC) are the main cause of traveler's diarrhea and
are significant pathogens affecting children and elderly individuals of developing countries.
The purpose of the study is to determine the safety of the ETEC-Cholera vaccine against the
E. coli responsible for the diarrhea. The study will enroll a total of 64 healthy volunteers,
18 to 45 years old at the Cincinnati Children's Hospital. The study will look at increasing
doses of the vaccine or placebo given to 4 groups of 16 subjects. Subjects will remain in the
inpatient unit for observation study days - 1 through 9 during which stool samples will be
collected. Subjects will return to the clinic on study days 10, 14, 21, and 28 for required
follow up. Subjects will be contacted by telephone months 2, 4, and 6 to assess for side
effects of the study drug. All subjects will be treated with Cipro, an antibiotic, for 5
days. Subjects will participate in study related procedures for up to 8 months.
observation study days - 1 through 9. Subjects will return to the study clinic on study days
10, 14, 21, and 28 for required evaluations. Subjects will be contacted by telephone at 2, 4,
and 6 months following study drug administration to assess for any new medications, changes
in concomitant medication regimens (both prescription and over the counter medications), and
the occurrence of adverse events. The primary objective of this study will be to assess the
safety of a combined ETEC-cholera vaccine (Peru-15-pCTB) when administered as a single oral
dose over a range of doses in healthy adult subjects compared to placebo at day 28
post-vaccination. The secondary objectives will be: to assess long-term safety follow-up from
immunization through Month 6 post-vaccination; to evaluate the immunogenicity of a single
oral dose of ETEC-cholera vaccine over a range of doses in healthy adult subjects; and to
evaluate the shedding profile of the ETEC-cholera vaccine organisms in stool for a period of
7 days. The primary endpoint of the study is the safety of ETEC-cholera vaccine as assessed
by the incidence and severity of adverse events (AE) and changes in laboratory and clinical
parameters through the day 28 post-vaccination visit. The secondary endpoints include
immunogenicity as assessed by changes in vibriocidal antibody titer, anti-cholera toxin
B-subunit antibody titer, and anti-labile toxin antibody titer.
Inclusion Criteria:
- Male or female age 18-45, inclusive.
- Healthy as judged by the Principal Investigator (PI) and determined by medical
history, physical examination, vital signs, screening laboratories, and medication
history.
- Capable of understanding, consenting and complying with the entire study protocol
including the inpatient period.
- Female subjects must be of non-childbearing potential, or if of childbearing potential
(as determined by the investigator) must be practicing abstinence or using an
effective licensed method of birth control (e. g., oral contraceptives; diaphragm or
condom in combination with contraceptive jelly, cream, or foam; intrauterine
contraceptive device, or Depo-Provera; skin patch; vaginal ring or cervical cap) for
30 days prior to vaccination and must agree to continue such precautions during the
study and for 30 days after the Day 28 study visit.
- Male subjects must agree not to father a child during the study and for 90 days after
the Day 0 study visit.
- Provide voluntary written informed consent and attained at least 70% on an examination
about the study on the first attempt.
- Have normal screening laboratories for SGPT (ALT), creatinine, sodium, potassium,
total white blood count (WBC), hemoglobin, neutrophils, lymphocytes, platelets, urine
protein, urine glucose and urine RBCs.
Exclusion Criteria:
- Women who are pregnant or lactating or have a positive serum pregnancy test at
screening or upon admission to inpatient facility.
- Subjects who are immunocompromised or immunodeficient, or have had a prior malignancy
(exception: a history of basal cell or squamous cell carcinoma in remission without
treatment for more than 5 years prior to study entry).
- History of clinically significant chronic illness or other condition requiring chronic
medication therapy.
- History of malabsorption or maldigestion disorder (e. g., celiac sprue), major
gastrointestinal (GI) surgery, or any other chronic GI disorders that would interfere
with the study or the investigational product.
- Any current or past use of immunosuppressive medications including inhaled steroids
(e. g., for asthma) within 6 months of screening.
- Recent (e. g., within 5 years) history of travel to a cholera or ETEC endemic area,
raised in a cholera or ETEC endemic area or a history of raising a child from an
endemic area for cholera or ETEC. Individuals who may work with V. cholerae or ETEC
in the laboratory are also excluded.
- Vaccination against or infection with cholera or E. coli, or participation in a
clinical trial using cholera or ETEC vaccine or organisms at any time.
- History of drug or alcohol abuse any time in the last 6 months.
- Presence of HIV antibody, hepatitis C antibody, or positive hepatitis B surface
antigen.
- Clinically abnormal screening electrocardiogram (ECG) defined as pathologic Q waves
and significant ST-T wave changes; criteria for left ventricular hypertrophy; and any
non-sinus rhythm excluding isolated premature atrial contractions.
- Presence of bacterial or parasitic pathogens in stool culture in a screening stool
examination.
- IgA deficiency.
- A change in subject's normal stool pattern within 3 months of screening visit. A
normal stool pattern is defined as 3 to 21 stools per week.
- Any known allergy or sensitivity to Ciprofloxacin.
- Have any known allergy to components of the vaccine [M9 minimal salts, glycerin,
dextrose anhydrous, sodium chloride, peptone (vegetable) acid hydrolysate, magnesium
sulfate heptahydrate, and aspartame] or placebo/bicarbonate buffer (water, sodium
bicarbonate, ascorbic acid, and aspartame).
- Any medical illness requiring a new prescription medication or hospitalization during
the screening period or having a temperature greater than or equal to 38. 0 degrees C
during the 2 weeks prior to investigational product administration (Day 0).
- Administration of any vaccine, licensed or investigational, or any investigational
product within 30 days of investigational product administration (Day 0) or any plan
for participation in another investigational trial during this study.
- Use of antibiotics within 7 days of investigational product administration (Day 0).
- Use of laxatives for hard or infrequent stools one or more times in a month in any of
the 3 months prior to enrollment.
- Use of any H2 receptor antagonists (e. g., Tagamet®, Zantac®, and Pepcid®), proton pump
inhibitors (e. g., Prilosec® OTC, Protonix®, and Prevacid®), or prescription acid
suppression medication or over-the-counter (OTC) antacids within 72 hours of
investigational product administration.
- Use of prescription and OTC medications that contain acetaminophen, aspirin,
ibuprofen, and other nonsteroidal anti-inflammatory drugs within 48 hours prior to
investigational product administration.
- Employment as a commercial food handler, day care worker, or health care worker
involved in direct patient contact. Subjects with children less than 2 years old at
home or with household contacts who are immunocompromised, pregnant or
breast-feeding.
- Any other condition or responsibility, such as a medical, psychiatric, or social
condition or occupational responsibility that, in the judgment of the investigator,
would interfere with or serve as a contraindication to the subject's participation in
the protocol or assessment of the investigational product.
- Subjects who are unwilling or unable to cease smoking for the duration of the
inpatient stay.
- Subjects who are unable to pass a test that describes cholera and ETEC diarrhea and
explains the requirements of the clinical trial. Subjects must score a minimum of 70%
upon the first attempt.
- Subjects will be excluded if their screening laboratory test results fall outside of
the laboratory normal; however, transaminase levels (ALT) and creatinine levels (Cr)
below the lower limit of "normal" will not be an exclusion criterion.
- Subjects with Phenylketonuria (PKU) will be excluded because the investigational
product (vaccine) bicarbonate buffer contains aspartame.
