A Study of Live Oral Cholera Vaccine, PXVX200 in Healthy Older Adults

A Phase III Randomized, Double-blind, Placebo-controlled Study in Older Adults to Assess Immunogenicity and Clinical Acceptability of a Single-dose of the Live Oral Cholera Vaccine Candidate PXVX0200 O1 Serotype Inaba Strain CVD 103-HgR

Demonstrate that the vaccine offers protection based on antibody levels in older adults and is similar to antibody levels in adults aged 18-45 following vaccination with PXVX0200.

Study Overview

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

Detailed Description

Demonstrate that seroconversion by classical Inaba vibriocidal antibody at Day 11 in older adults ages 46-64 years (inclusive) was non inferior to seroconversion at Day 11 in younger adults ages 18-45 years following vaccination with PXVX0200.

• Study Type: Interventional
• Enrollment (Actual): 398
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical
    • Miami, Florida, United States, 33143
      • Miami Research Associates
    • Palm Beach, Florida, United States, 33409
      • Palm Beach Research Center
  • 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
  • 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
  • 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
  • Vermont
    • Burlington, Vermont, United States, 05405
      • University of Vermont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years to 64 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Able to understand the study and give written consent.
2. Healthy male and female adults, age 46-64 years (inclusive) without significant medical history, physical, or abnormal screening laboratory test results at screening.
3. Women of childbearing potential must have had a negative urine pregnancy test at screening, prior to vaccination. Female subjects must be of non-childbearing potential (as defined as surgically sterile or postmenopausal for more than 1 year), or if of childbearing potential must be practicing abstinence or using an effective licensed method of birth control (eg, use hormonal or barrier birth control such as implants, injectables, combined oral contraceptives, intrauterine devices [IUDs], cervical sponges, diaphragms, condoms with spermicidal agents; or must have a vasectomized partner) within 2 months of vaccination and must agree to continue such precautions during the study.
4. Willing and able to comply with the study requirements and procedures.

Exclusion Criteria:

1. Currently active unstable or undiagnosed medical conditions including immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, neurologic illness, psychiatric disorder requiring hospitalization, current drug or alcohol abuse. Examples of unstable or undiagnosed medical conditions including unstable angina pectoris, shortness of breath on exertion without clear etiology and chronic renal failure requiring dialysis. Examples of conditions that do not meet exclusion criteria include mild controlled hypertension, mild controlled asthma, and treated depression without hospitalization.
2. Abnormal stool pattern defined as fewer than 3 stools per week or more than 2 stools per day in past 6 months.
3. Regular use of laxatives in the past 6 months.
4. Previously received a licensed or investigational cholera vaccine.
5. History of cholera or enterotoxigenic E. coli infection (natural infection or experimental challenge).
6. Travel to a cholera-endemic area in the previous 5 years.
7. Received or plans to receive any other licensed vaccines, except for seasonal influenza vaccine, from 14 days prior to the study vaccination through to 29 days after vaccination.
8. Received or plans to receive antibiotics or chloroquine within 14 days prior to the study vaccination through to 29 days after vaccination.
9. Recipient of bone marrow or solid organ transplant.
10. Use of systemic chemotherapy in the previous 5 years prior to the study.
11. Malignancy (excluding non-melanotic skin cancers) or lymphoproliferative disorders diagnosed or treated during the past 5 years.
12. Received or plans to receive systemic immunosuppressive therapy, radiation therapy, parenteral or high-dosage inhaled steroids (>800 µg/day of beclomethasone diproprionate or equivalent) within 6 months prior to the study vaccination through to Day 29.
13. History of Guillain-Barré Syndrome.
14. Pregnant or nursing.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PXVX0200 in Older Adults; PXVX0200 Single dose; liquid suspension after reconstitution with buffer; > 2x10^8 CFU in a liquid suspension	Biological: PXVX0200
Placebo Comparator: Placebo in Older Adults; Placebo physiological saline	Biological: Placebo
Other: Historical Control: Adults Aged 18-45; This arm consists of historical data from subjects who received a single dose of PXVX0200 in study PXVX-VC-200-004. The data was included in study PXVX-VC-200-005 as a comparator bridging population for the Day 11 seroconversion. NCT02094586 PubMed ID:29317118	Biological: PXVX0200

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion Rate at Day 11	The seroconversion rate is defined as the percentage of subjects with a 4-fold or greater rise over baseline Day 1 Serum Vibriocidal Antibody (SVA) titer against the classical Inaba biotype of V. cholerae at Day 11 following one dose of Vaxchora vaccine. The hypothesis was that the seroconversion rate would be non-inferior to the seroconversion rate at Day 11 in adults between the ages of 18 and 45 years.	Day 11

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titer (GMT)	The Day 11 vibriocidal GMTs were compared between older and younger adults.	Day 11

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Seroconversion Through Day 29 Compared to Day 11 for Younger Adults	The cumulative seroconversion through Day 29 for older adults was compared to the Day 11 seroconversion for the younger adults aged 18 - 45 yrs. Seroconversion is defined as a 4-fold rise in antibody titer relative to baseline values.	Day 29
Mean Fold Change in Vibriocidal Antibody Titer Between Day 1 and Day 11	The mean log2 fold change between Day 1 and Day 11 in classical Inaba vibriocidal antibody titer attained by older adults was compared to the younger adults aged 18 - 45 yrs.	Day 11
Seroconversion Against Other V. Cholerae Biotypes/Serotypes	Seroconversion of the vibriocidal antibody response against 4 V. cholerae biotypes/serotypes - classical Inaba, El Tor Inaba, classical Ogawa and El Tor Ogawa was assessed.	Day 11
Anti-CT Antibody Response in Older Adults	The seroconversion of anti-Cholera Toxin (CT) antibody response in older adults was assessed. Seroconversion is defined as a 4-fold rise in anti-CT antibody titer relative to baseline values.	Day 11

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, Bennett S, Hunt KM, Simon JK, Gurwith M. Age-related immunogenicity and reactogenicity of live oral cholera vaccine CVD 103-HgR in a randomized, controlled clinical trial. Vaccine. 2019 Mar 7;37(11):1389-1397. doi: 10.1016/j.vaccine.2019.01.077. Epub 2019 Feb 13.

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 25, 2014
• First Submitted That Met QC Criteria: March 31, 2014
• First Posted (Estimated): April 1, 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-200-005

Plan for Individual participant data (IPD)

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