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

Primary Purpose

Cholera

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
PXVX0200
placebo
Sponsored by
Bavarian Nordic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cholera

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • University of Maryland Baltimore
  • Cincinnati Children'S Hospital Medical Center
  • University of Vermont

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

PXVX0200

Placebo

Arm Description

Biological: PXVX0200 Single dose; liquid suspension after reconstitution with buffer; 5x10^8 CFU

Biological: Placebo physiological saline

Outcomes

Primary Outcome Measures

% 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.
% 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.

Secondary Outcome Measures

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.
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.
% 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.
% 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.
% of Participants With Fever Following the 10 Day Cholera Challenge
Incidence of mild or worse fever following the 10 day cholera challenge.
% of Participants With Fever Following the 90 Day Cholera Challenge
Incidence of mild or worse fever following the 90 day cholera 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.
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
# 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.
# 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
% 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).

Full Information

First Posted
July 5, 2013
Last Updated
June 26, 2023
Sponsor
Bavarian Nordic
Collaborators
Emergent BioSolutions
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1. Study Identification

Unique Protocol Identification Number
NCT01895855
Brief Title
Safety and Efficacy Challenge Study of Live Oral Cholera Vaccine Candidate,PXVX0200, to Prevent Cholera
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bavarian Nordic
Collaborators
Emergent BioSolutions

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cholera

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
197 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PXVX0200
Arm Type
Experimental
Arm Description
Biological: PXVX0200 Single dose; liquid suspension after reconstitution with buffer; 5x10^8 CFU
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Biological: Placebo physiological saline
Intervention Type
Biological
Intervention Name(s)
PXVX0200
Intervention Description
Single dose; liquid suspension after reconstitution with buffer; 5x10^8
Intervention Type
Biological
Intervention Name(s)
placebo
Primary Outcome Measure Information:
Title
% of Participants With Moderate to Severe Diarrhea
Description
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.
Time Frame
Ten days after vaccination
Title
% of Participants With Moderate to Severe Diarrhea
Description
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.
Time Frame
Ninety days after vaccination
Secondary Outcome Measure Information:
Title
Total Weight of Diarrheal Stools Following the 10 Day Cholera Challenge
Description
Total weight (converted to volume) per subject of diarrheal stools measured from subjects with diarrhea following the 10 day cholera challenge.
Time Frame
Through 10 Days following challenge
Title
Total Weight of Diarrheal Stools Following the 90 Day Cholera Challenge
Description
Total weight (converted to volume) per subject of diarrheal stools measured from subjects with diarrhea following the 90 day cholera challenge.
Time Frame
Through 10 Days following challenge
Title
% of Participants With Diarrhea of Any Severity Following a 10 Day Cholera Challenge
Description
Incidence of mild or worse (any severity) diarrhea following the 10 day cholera challenge.
Time Frame
Through 10 Days following challenge
Title
% of Participants With Diarrhea of Any Severity Following a 90 Day Challenge
Description
Incidence of mild or worse (any severity) diarrhea following the 90 day cholera challenge.
Time Frame
Through 10 Days following challenge
Title
% of Participants With Fever Following the 10 Day Cholera Challenge
Description
Incidence of mild or worse fever following the 10 day cholera challenge.
Time Frame
Through 10 Days following challenge
Title
% of Participants With Fever Following the 90 Day Cholera Challenge
Description
Incidence of mild or worse fever following the 90 day cholera challenge.
Time Frame
Through 10 Days following challenge
Title
Number of Days With Fecal Shedding Following 10 Day Challenge
Description
Number of days of fecal shedding of wild type V. cholerae following 10 Day Challenge.
Time Frame
Through 10 Days post challenge
Title
Number of Days With Fecal Shedding Following 90 Day Challenge
Description
Number of days of fecal shedding of wild type V. cholerae following 90 Day Challenge
Time Frame
Through 10 days following challenge
Title
# of Days With Positive Stool Culture Following 10 Day Cholera Challenge
Description
Total number of days with a positive stool culture following the 10 Day Cholera challenge.
Time Frame
Through 10 Days following challenge
Title
# of Days With Positive Stool Culture Following 90 Day Cholera Challenge
Description
Total number of days with a positive stool culture following 90 Day Cholera Challenge
Time Frame
Through 10 Days following challenge
Title
% of Participants With Reactogenicity, Diarrhea, Fever or Unsolicited Adverse Events Following Vaccination
Description
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).
Time Frame
Following vaccination (Days 1 - 8) and to Day 29

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James McCarty, MD
Organizational Affiliation
Emergent BioSolutions
Official's Role
Study Director
Facility Information:
Facility Name
University of Maryland Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Cincinnati Children'S Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
University of Vermont
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05405
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
27001804
Citation
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.
Results Reference
result
PubMed Identifier
29655627
Citation
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.
Results Reference
result
PubMed Identifier
28566334
Citation
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.
Results Reference
result
PubMed Identifier
31743334
Citation
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.
Results Reference
derived
PubMed Identifier
29624592
Citation
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.
Results Reference
derived

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

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