Safety and Immunogenicity of the Live Oral Cholera Vaccine Candidate PXVX0200

Study Overview
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Brief Summary
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The purpose of this study is to compare the safety and immunogenicity of a single dose of the PXVX0200 live cholera vaccine versus placebo in volunteers (Vaccinees) and whether PXVX0200, which is a live attenuated bacteria, can be transmitted to other adults living in the same household.

Detailed Description
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Approximately 60 subjects and up to 120 household contacts will be enrolled in the United States. Vaccinees will be randomly assigned to receive either PXVX0200 or placebo in a 5:1 ratio and will be followed for 180 days postdose.

Official Title
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A Phase 1 Randomized, Double-Blind Placebo Controlled Study to Evaluate the Safety and Immunogenicity of the LIve Oral Cholera Vaccine Candidate PXVX0200 Vibrio Cholerae Serotype 01 Inaba CVD 103-HgR Vaccine Strain

Conditions
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Cholera

Intervention / Treatment
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* Biological: PXVX0200
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Men or women, age 18 to 50 years (inclusive) without significant medical history, physical or clinical lab abnormalities (as per protocol defined ranges) Women of childbearing potential must have negative urine pregnancy test and must be willing to use adequate birth control for 2 months following vaccination and have additional pregnancy tests as indicated Vaccinees must live alone or have no more than two household contacts willing to sign informed consent and participate in the study Household contacts must be healthy (based on medical history) men or women aged 18-65 years (inclusive) Exclusion Criteria: Healthcare workers who have direct contact with patients who are immunodeficient, are HIV-positive, have unstable medical condition or are under the age of 18 Childcare workers who have direct contact with children who are 2 years of age or younger or those employed in the food service industry Resides with HHCs who are under the age of 18 or over the age of 65 Has abnormal stool pattern defined as fewer than 3 stools per week or more than 2 stools per day in past 6 months Has known allergy to, or known medical condition that precludes the use of both tetracycline or ciprofloxacin Previously received a licensed or investigational cholera vaccine Has history of cholera or enterotoxigenic E. coli infection (natural infection or experimental challenge) Travel to a cholera-endemic area and experienced symptoms consistent with traveler's diarrhea in the previous 5 years Received or plans to receive any other licensed vaccines from 14 days prior to the study vaccination until Day 28 Received or plans to receive antibiotics (other than protocol-specified) or chloroquine within 14 days prior to the study vaccination through to Day 28

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Approx 2 grams of lactose reconstituted in water<br>|
| Experimental: PXVX0200<br> | Biological: PXVX0200<br>* Single dose; liquid suspension after reconstitution with buffer; 2x108 to 2x109 CFU in a liquid suspension<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety | Safety defined as frequency and severity of vaccine-related reactogenicity events and reported AEs | Day 0-180 | 
| Immunogenicity | Immunogenicity as defined as rate of seroconversion (4-fold rise) of serum Inaba vibriocidal antibody and initial estimates of between subject variability of vibriocidal antibody response | Day 0-28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kinetics | Kinetics of serum Inaba vibriocidal antibody after 1 oral dose of CVD 103-HgR | Day 0-28 | 
| Serum anti-cholera toxin (CT) IgG antibody conversion rates | Anti-cholera toxin IgG antibody conversion rates | Day 0-28 | 
| Fecal shedding | Fecal shedding of CVD 103-HgR by vaccine recipient | Day 0-7 | 
| Vibriocidal seroconversion and shedding of CVD 103-HgR in household contacts | Vibriocidal seroconversion and shedding of CVD 103-HgR in household contacts | Day 0-28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, Bacterial disease condition, Cholera