Safety and Immunogenicity of Peru-15-pCTB in Healthy Adult Subjects
A Randomized, Double-Blind, Placebo-Controlled Dose Escalation, Inpatient Phase I Study to Determine the Safety and Immunogenicity of a Single Oral Dose of a Combined Live, Attenuated, Enterotoxigenic Escherichia Coli (ETEC)-Cholera Vaccine (Peru-15 pCTB) in Healthy Adult Subjects
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Ohio
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Cincinnati, Ohio, United States, 45229-3039
- Cincinnati Children's Hospital Medical Center - Infectious Diseases
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT), creatinine, sodium, potassium, total white blood count (WBC), hemoglobin, neutrophils, lymphocytes, platelets, urine protein, urine glucose and urine red blood cells (RBC).
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 Enterotoxigenic Escherichia coli (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 Vibrio (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 (immunoglobulin) 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 Celsius 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® over the counter (OTC), Protonix®, and Prevacid®), or prescription acid suppression medication or 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 that are immunocompromised, pregnant or breast-feeding. -Any other condition or responsibili ty, 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 percent upon the first attempt. -Subjects will be excluded if their screening laboratory test results fall outside of the laboratory normal; however, transaminase levels [alanine aminotransferase (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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Cohort 1: vaccine dosage level 1 or placebo
Vaccine dose level 1: 1 X 10^7 colony forming unit (CFU) or placebo, treated with Cipro on days 7-11.
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500 milligrams(mg) will be administered orally twice daily for 5 days.
Live attenuated oral combined ETEC-cholera (Peru-15 pCTB) vaccine co-administered with bicarbonate buffer solution; vaccine dose levels 1 X 10^7; 1 X 10^8; 1 X 10^9; and 1 X 10^10.
Buffer solution: 2.5 grams (g) Sodium Bicarbonate powder, 1.65 g Ascorbic Acid and 25 mg Aspartame, in 100 milliliters (mL) water for injection.
|
|
Experimental: Cohort 2: vaccine dosage level 2 or placebo
Vaccine dose level 2: 1 X 10^8 CFU or placebo, treated with Cipro on days 7-11.
|
500 milligrams(mg) will be administered orally twice daily for 5 days.
Live attenuated oral combined ETEC-cholera (Peru-15 pCTB) vaccine co-administered with bicarbonate buffer solution; vaccine dose levels 1 X 10^7; 1 X 10^8; 1 X 10^9; and 1 X 10^10.
Buffer solution: 2.5 grams (g) Sodium Bicarbonate powder, 1.65 g Ascorbic Acid and 25 mg Aspartame, in 100 milliliters (mL) water for injection.
|
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Experimental: Cohort 3: vaccine dosage level 3 or placebo
Vaccine dose level 3: 1 X 10^9 CFU or placebo, treated with Cipro on days 7-11.
|
500 milligrams(mg) will be administered orally twice daily for 5 days.
Live attenuated oral combined ETEC-cholera (Peru-15 pCTB) vaccine co-administered with bicarbonate buffer solution; vaccine dose levels 1 X 10^7; 1 X 10^8; 1 X 10^9; and 1 X 10^10.
Buffer solution: 2.5 grams (g) Sodium Bicarbonate powder, 1.65 g Ascorbic Acid and 25 mg Aspartame, in 100 milliliters (mL) water for injection.
|
|
Experimental: Cohort 4: vaccine dosage level 4 or placebo
Vaccine dose level 4: 1 X 10^10 CFU or placebo, treated with Cipro on days 7-11.
|
500 milligrams(mg) will be administered orally twice daily for 5 days.
Live attenuated oral combined ETEC-cholera (Peru-15 pCTB) vaccine co-administered with bicarbonate buffer solution; vaccine dose levels 1 X 10^7; 1 X 10^8; 1 X 10^9; and 1 X 10^10.
Buffer solution: 2.5 grams (g) Sodium Bicarbonate powder, 1.65 g Ascorbic Acid and 25 mg Aspartame, in 100 milliliters (mL) water for injection.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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Adverse Events (AEs) will be graded according to standardized criteria.
Time Frame: Through the Day 28 post-vaccination visit.
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Through the Day 28 post-vaccination visit.
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Safety: physical examinations, interim medical history, solicited symptoms/subject memory aid, and laboratory evaluations.
Time Frame: Through the Day 28 post-vaccination visit.
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Through the Day 28 post-vaccination visit.
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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Immunogenicity will be assessed by changes in vibriocidal antibody titer, anti-Cholera toxin B-subunit antibody titer, and anti-Labile toxin antibody titer.
Time Frame: Days -1, 7, 10, 14, and 28.
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Days -1, 7, 10, 14, and 28.
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Stool shedding of the vaccine organisms will be assessed by qualitative and quantitative cultures.
Time Frame: Qualitative: Days 1-10, 14, 21, 28: Quantitative: Days 1-10.
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Qualitative: Days 1-10, 14, 21, 28: Quantitative: Days 1-10.
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Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Infections
- Gastrointestinal Diseases
- Gram-Negative Bacterial Infections
- Bacterial Infections
- Bacterial Infections and Mycoses
- Enterobacteriaceae Infections
- Gastroenteritis
- Escherichia coli Infections
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Protective Agents
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Micronutrients
- Anti-Bacterial Agents
- Cytochrome P-450 Enzyme Inhibitors
- Vitamins
- Antioxidants
- Cytochrome P-450 CYP1A2 Inhibitors
- Ciprofloxacin
- Ascorbic Acid
Other Study ID Numbers
- 07-0052
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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