Safety and Efficacy Challenge Study of Live Oral Cholera Vaccine Candidate,PXVX0200, to Prevent Cholera

Study Overview
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Brief Summary
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The purpose of the study is to determine if PXVX0200 is safe and effective in preventing cholera infection

Detailed Description
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A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Efficacy Trial of a Single Dose of Live Oral Cholera Vaccine Candidate, PXVX0200 CVD 103-HgR Strain, in Preventing Cholera following Challenge with Vibrio cholerae O1 El Tor Inaba 10 Days or 3 Months after Vaccination in volunteers aged 18-45 years

Official Title
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A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Efficacy Trial of a Single Dose Live Oral Cholera Vaccine, PXVX0200 CVD 103-HgR, in Preventing Cholera Following Challenge With Vibrio Cholerae 10 Days or 3 Months After Vaccination

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 45 years inclusive; normal medical history and physical examination; and no clinically significant abnormalities from: urine dipstick for glucose, protein, and blood complete blood count, serum hepatic transaminases, total bilirubin (direct if abnormal), creatinine, electrolytes, albumin, or electrocardiogram. Women must have a negative pregnancy test. Exclusion Criteria: travel to a cholera endemic area in the previous 5 years; abnormal stool pattern or regular use of laxatives; history of eating disorders (such as bulimia), anal or rectal disorders, allergy to tetracycline and/or ciprofloxacin; history of cholera or enterotoxigenic E. coli challenge or infection; current or recent antibiotic use; pregnancy or nursing; positive serology for HIV, hepatitis B antigen, or hepatitis C; any immunosuppressive medical condition; history of hospitalization for psychiatric illness or use of specific psychiatric drugs.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PXVX0200<br>Biological: PXVX0200 Single dose; liquid suspension after reconstitution with buffer; 5x10^8 CFU | Biological: PXVX0200<br>* Single dose; liquid suspension after reconstitution with buffer; 5x10^8<br>|
| Placebo Comparator: Placebo<br>Biological: Placebo physiological saline | Biological: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % of Participants With Moderate to Severe Diarrhea | Determine whether a single dose of PXVX0200 provides significantly greater protection than placebo against a challenge with virulent V. cholerae O1 El Tor Inaba at 10 days after vaccination. The primary endpoint was the occurrence of moderate or severe (>/= 3 liters) diarrhea. | Ten days after vaccination | 
| % of Participants With Moderate to Severe Diarrhea | Determine whether a single dose of PXVX0200 provides significant greater protection than placebo against a challenge with virulent V. cholerae O1 El Tor Inaba at 3 months after vaccination. The primary endpoint was the occurrence of moderate or severe (>/= 3 liters) of diarrhea. | Ninety days after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Weight of Diarrheal Stools Following the 10 Day Cholera Challenge | Total weight (converted to volume) per subject of diarrheal stools measured from subjects with diarrhea following the 10 day cholera challenge. | Through 10 Days following challenge | 
| Total Weight of Diarrheal Stools Following the 90 Day Cholera Challenge | Total weight (converted to volume) per subject of diarrheal stools measured from subjects with diarrhea following the 90 day cholera challenge. | Through 10 Days following challenge | 
| % of Participants With Diarrhea of Any Severity Following a 10 Day Cholera Challenge | Incidence of mild or worse (any severity) diarrhea following the 10 day cholera challenge. | Through 10 Days following challenge | 
| % of Participants With Diarrhea of Any Severity Following a 90 Day Challenge | Incidence of mild or worse (any severity) diarrhea following the 90 day cholera challenge. | Through 10 Days following challenge | 
| % of Participants With Fever Following the 10 Day Cholera Challenge | Incidence of mild or worse fever following the 10 day cholera challenge. | Through 10 Days following challenge | 
| % of Participants With Fever Following the 90 Day Cholera Challenge | Incidence of mild or worse fever following the 90 day cholera challenge. | Through 10 Days following challenge | 
| Number of Days With Fecal Shedding Following 10 Day Challenge | Number of days of fecal shedding of wild type V. cholerae following 10 Day Challenge. | Through 10 Days post challenge | 
| Number of Days With Fecal Shedding Following 90 Day Challenge | Number of days of fecal shedding of wild type V. cholerae following 90 Day Challenge | Through 10 days following challenge | 
| # of Days With Positive Stool Culture Following 10 Day Cholera Challenge | Total number of days with a positive stool culture following the 10 Day Cholera challenge. | Through 10 Days following challenge | 
| # of Days With Positive Stool Culture Following 90 Day Cholera Challenge | Total number of days with a positive stool culture following 90 Day Cholera Challenge | Through 10 Days following challenge | 
| % of Participants With Reactogenicity, Diarrhea, Fever or Unsolicited Adverse Events Following Vaccination | Incidence and severity of signs and symptoms of reactogenicity such as diarrhea, and fever following vaccination (through Day 8). Incidence and severity of unsolicited adverse events following vaccination (through Day 29). | Following vaccination (Days 1 - 8) and to Day 29 |