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

• ClinicalTrials.gov Identifier: NCT01895855
• Recruitment Status: Completed
• First Posted: July 11, 2013
• Results First Posted: April 1, 2021
• Last Update Posted: April 1, 2021
• Sponsor: Emergent BioSolutions
• Information provided by (Responsible Party): Emergent BioSolutions

Tracking Information

• First Submitted Date: July 5, 2013
• First Posted Date: July 11, 2013
• Results First Submitted Date: July 5, 2018
• Results First Posted Date: April 1, 2021
• Last Update Posted Date: April 1, 2021
• Study Start Date: September 2013
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 5, 2021)

• % of Participants With Moderate to Severe Diarrhea [ Time Frame: Ten days after vaccination ]
  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 [ Time Frame: Ninety days after vaccination ]
  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.

Original Primary Outcome Measures (submitted: July 10, 2013)

• Ten day cholera challenge [ Time Frame: Ten days after vaccination ]
  Determine whether a single dose of PXVX0200 provides significant protection against a challenge with virulent V. cholerae O1 El Tor Inaba at 10 days after vaccination.
• Ninety day cholera challenge [ Time Frame: Ninety days after vaccination ]
  Determine whether a single dose of PXVX0200 provides significant protection against a challenge with virulent V. cholerae O1 El Tor Inaba at 3 months after vaccination.

Current Secondary Outcome Measures (submitted: March 5, 2021)

• Total Weight of Diarrheal Stools Following the 10 Day Cholera Challenge [ Time Frame: Through 10 Days following 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 [ Time Frame: Through 10 Days following 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 [ Time Frame: Through 10 Days following 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 [ Time Frame: Through 10 Days following 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 [ Time Frame: Through 10 Days following challenge ]
  Incidence of mild or worse fever following the 10 day cholera challenge.
• % of Participants With Fever Following the 90 Day Cholera Challenge [ Time Frame: Through 10 Days following challenge ]
  Incidence of mild or worse fever following the 90 day cholera challenge.
• Number of Days With Fecal Shedding Following 10 Day Challenge [ Time Frame: Through 10 Days post 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 [ Time Frame: Through 10 days following 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 [ Time Frame: Through 10 Days following 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 [ Time Frame: Through 10 Days following 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 [ Time Frame: Following vaccination (Days 1 - 8) and to Day 29 ]
  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).

Original Secondary Outcome Measures (submitted: July 10, 2013)

• disease severity [ Time Frame: from vaccination through day 180 ]
  Total weight of diarrheal stools Incidence of diarrhea of any severity Incidence of fever Incidence of fecal shedding of wild type Vibrio cholerae Peak concentration of wild type Vibrio cholerae detected in stool
• tolerability of vaccine [ Time Frame: following vaccination through 180 days ]
  Incidence and severity of signs and symptoms of reactogenicity such as diarrhea, and fever Incidence and severity of unsolicited adverse events

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Cholera

Intervention

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

Study Arms

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

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 5, 2021): 197
• Original Estimated Enrollment (submitted: July 10, 2013): 210
• Actual Study Completion Date: November 2014
• Actual Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01895855
• Other Study ID Numbers: PXVX-VC-200-003
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Emergent BioSolutions
• Original Responsible Party: Same as current
• Current Study Sponsor: Emergent BioSolutions
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: James McCarty, MD; Emergent BioSolutions

• PRS Account: Emergent BioSolutions
• Verification Date: March 2021