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

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

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

Study Overview

• Status: Completed
• Conditions: Cholera
• Intervention / Treatment: Biological: placebo; Biological: PXVX0200

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 197
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Baltimore
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Vermont
    • Burlington, Vermont, United States, 05405
      • University of Vermont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bavarian Nordic
• Collaborators: Emergent BioSolutions
• Investigators: Study Director: James McCarty, MD, Emergent BioSolutions

Publications and helpful links

General Publications

• Chen WH, Cohen MB, Kirkpatrick BD, Brady RC, Galloway D, Gurwith M, Hall RH, Kessler RA, Lock M, Haney D, Lyon CE, Pasetti MF, Simon JK, Szabo F, Tennant S, Levine MM. Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio cholerae O1 El Tor. Clin Infect Dis. 2016 Jun 1;62(11):1329-1335. doi: 10.1093/cid/ciw145. Epub 2016 Mar 21.
• Haney DJ, Lock MD, Gurwith M, Simon JK, Ishioka G, Cohen MB, Kirkpatrick BD, Lyon CE, Chen WH, Sztein MB, Levine MM, Harris JB. Lipopolysaccharide-specific memory B cell responses to an attenuated live cholera vaccine are associated with protection against Vibrio cholerae infection. Vaccine. 2018 May 11;36(20):2768-2773. doi: 10.1016/j.vaccine.2018.04.011. Epub 2018 Apr 11.
• Haney DJ, Lock MD, Simon JK, Harris J, Gurwith M. Antibody-Based Correlates of Protection Against Cholera Analysis of a Challenge Study in a Cholera-Naive Population. Clin Vaccine Immunol. 2017 May 31;24(8):e00098-17. doi: 10.1128/CVI.00098-17. Online ahead of print.
• Hossain M, Islam K, Kelly M, Mayo Smith LM, Charles RC, Weil AA, Bhuiyan TR, Kovac P, Xu P, Calderwood SB, Simon JK, Chen WH, Lock M, Lyon CE, Kirkpatrick BD, Cohen M, Levine MM, Gurwith M, Leung DT, Azman AS, Harris JB, Qadri F, Ryan ET. Immune responses to O-specific polysaccharide (OSP) in North American adults infected with Vibrio cholerae O1 Inaba. PLoS Negl Trop Dis. 2019 Nov 19;13(11):e0007874. doi: 10.1371/journal.pntd.0007874. eCollection 2019 Nov.
• Islam K, Hossain M, Kelly M, Mayo Smith LM, Charles RC, Bhuiyan TR, Kovac P, Xu P, LaRocque RC, Calderwood SB, Simon JK, Chen WH, Haney D, Lock M, Lyon CE, Kirkpatrick BD, Cohen M, Levine MM, Gurwith M, Harris JB, Qadri F, Ryan ET. Anti-O-specific polysaccharide (OSP) immune responses following vaccination with oral cholera vaccine CVD 103-HgR correlate with protection against cholera after infection with wild-type Vibrio cholerae O1 El Tor Inaba in North American volunteers. PLoS Negl Trop Dis. 2018 Apr 6;12(4):e0006376. doi: 10.1371/journal.pntd.0006376. eCollection 2018 Apr.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: July 5, 2013
• First Submitted That Met QC Criteria: July 10, 2013
• First Posted (Estimated): July 11, 2013

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 26, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Vibrio Infections; Cholera
• Other Study ID Numbers: PXVX-VC-200-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO