A Phase 3 Lot to Lot Consistency Study of Live Oral Cholera Vaccine, PXVX0200 in Healthy Adults

Phase 3 Randomized, Double-blind, Placebo-Controlled 3-Lot Study in Healthy Volunteers to Assess Immunogenicity, & Acceptability of a Single-dose of Live Oral Cholera Vaccine, Vibrio Cholerae O1 Serotype Inaba Vaccine Strain CVD 103-HgR

The primary goal of this Phase III study is to compare 3 lots for consistency of manufacture.

Study Overview

• Status: Completed
• Conditions: Cholera
• Intervention / Treatment: Biological: Placebo; Biological: PXVX0200 Lot A; Biological: PXVX0200 Lot B; Biological: PXVX0200 Lot C

Detailed Description

The primary goal of this Phase III study is to compare three lots for consistency of manufacture.

• Study Type: Interventional
• Enrollment (Actual): 3146
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4006
      • QIMR Berghofer Medical Research Institiue
    • Sherwood, Queensland, Australia, 4035
      • AUS Trials Pty Ltd
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • CMAX
  • Victoria
    • Malvern East, Victoria, Australia, 3145
      • Emeritis Research
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Clinical Reseach Consortium Arizona
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research
    • Miami, Florida, United States, 33143
      • Miami Research Associates
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Johnson County Clin-Trials
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
    • Lexington, Kentucky, United States, 40509
      • Central Kentucky Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02218
      • Boston University
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Center for Pharmaceutical Research
    • Saint Louis, Missouri, United States, 63104
      • St. Louis University
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Clinical Research Consortium Las Vegas
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Lion Research
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research
  • Texas
    • Dallas, Texas, United States, 75234
      • Research Across America
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Jean Brown Research

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
• 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;
• Currently active unstable or undiagnosed medical conditions
• current or recent antibiotic use;
• pregnancy or nursing;
• Previously received a licensed or investigational cholera vaccine
• History of cholera or enterotoxigenic E. coli infection
• History of Guillain-Barré Syndrome
• Received or plans to receive any other licensed vaccines, except for seasonal influenza
• Recipient of bone marrow or solid organ transplant
• Malignancy (excluding non-melanotic skin cancers) or lymphoproliferative disorders diagnosed or treated during the past 5 years
• Use of systemic chemotherapy in the previous 5 years prior to the study
• any immunosuppressive medical condition

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PXVX0200 Lot A; PXVX0200 (Lot P700-1CA03) Single dose; liquid suspension after reconstitution with buffer; > 2x10^8 CFU in a liquid suspension	Biological: PXVX0200 Lot A; Lot P700-1CA03
Experimental: PXVX0200 Lot B; PXVX0200 (Lot P700-3CA03) Single dose; liquid suspension after reconstitution with buffer; > 2x10^8 CFU in a liquid suspension	Biological: PXVX0200 Lot B; Lot P700-3CA03
Experimental: PXVX0200 Lot C; PXVX0200 (Lot P700-6BA03) Single dose; liquid suspension after reconstitution with buffer; > 2x10^8 CFU in a liquid suspension	Biological: PXVX0200 Lot C; Lot P700-6BA03
Placebo Comparator: Placebo; Placebo physiological saline	Biological: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Ratio (GMR) at Day 11 for Vaccine Lots A and B	The primary analysis consisted of three between-lot equivalence tests of serum vibriocidal antibody titer measured at Day 11. The GMT of each lot - µA, µB, and µC - was calculated by first log-transforming (base 10) the serum vibriocidal antibody titers, computing the means of the transformed data by lot, and then exponentiating the log-scale means to return to the original, untransformed scale. The resulting GMTs were combined to form three geometric mean ratios: µA/µB, µA/µC, and µB/µC.The ratios were required to be within +/- 50% of each other lot with 95% confidence, which implied that the limits of the 95% confidence interval on each pairwise GMR had to be within 0.67 - 1.5. Placebo GMT values were not included in the primary analysis.	Day 11
Geometric Mean Ratio (GMR) at Day 11 for Vaccine Lots B and C	The primary analysis consisted of three between-lot equivalence tests of serum vibriocidal antibody titer measured at Day 11. The GMT of each lot - µA, µB, and µC - was calculated by first log-transforming (base 10) the serum vibriocidal antibody titers, computing the means of the transformed data by lot, and then exponentiating the log-scale means to return to the original, untransformed scale. The resulting GMTs were combined to form three geometric mean ratios: µA/µB, µA/µC, and µB/µC.The ratios were required to be within +/- 50% of each other lot with 95% confidence, which implied that the limits of the 95% confidence interval on each pairwise GMR had to be within 0.67 - 1.5.	Day 11
Geometric Mean Ratio (GMR) at Day 11 for Vaccine Lots A and C	The primary analysis consisted of three between-lot equivalence tests of serum vibriocidal antibody titer measured at Day 11. The GMT of each lot - µA, µB, and µC - was calculated by first log-transforming (base 10) the serum vibriocidal antibody titers, computing the means of the transformed data by lot, and then exponentiating the log-scale means to return to the original, untransformed scale. The resulting GMTs were combined to form three geometric mean ratios: µA/µB, µA/µC, and µB/µC.The ratios were required to be within +/- 50% of each other lot with 95% confidence, which implied that the limits of the 95% confidence interval on each pairwise GMR had to be within 0.67 - 1.5.	Day 11

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SVA Seroconversion at Day 11	Percentage of subjects who demonstrated a ≥4-fold rise over baseline in serum vibriocidal antibody (SVA) at Day 11	Day 11
SVA and Anti-CT IgG GMT at Day 1, 11, 29, 91 and 181	GMTs of vibriocidal antibody and anti-CT IgG concentrations at Days 1, 11, 29, 91, and 181.	Day 1 - 181
SVA and Anti-CT IgG Seroconversion at Day 1, 11, 29, 91 & 181	Proportion of subjects who demonstrated a ≥4-fold rise over baseline in vibriocidal antibody and anti-CT IgG concentration from baseline at Days 1, 11, 29, 91, and 181. Day 1 not reported as seroconversion on Day 1 not applicable.	Day 1 - 181
Adverse Events	Incidence and severity of signs and symptoms of reactogenicity such as diarrhea, fever & vomiting were collected from Day 1 - 8. Incidence and severity of unsolicited adverse events were collected till Day 29.	Day 1 - 29

Collaborators and Investigators

• Sponsor: Bavarian Nordic
• Collaborators: Emergent BioSolutions
• Investigators: Study Director: James McCarty, MD, Emergent Travel Health Inc.

Publications and helpful links

General Publications

• McCarty JM, Lock MD, Hunt KM, Simon JK, Gurwith M. Safety and immunogenicity of single-dose live oral cholera vaccine strain CVD 103-HgR in healthy adults age 18-45. Vaccine. 2018 Feb 1;36(6):833-840. doi: 10.1016/j.vaccine.2017.12.062. Epub 2018 Jan 6.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: March 20, 2014
• First Submitted That Met QC Criteria: March 20, 2014
• First Posted (Estimated): March 24, 2014

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-200-004

Plan for Individual participant data (IPD)

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