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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Cholera

Intervention / Treatment
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* Biological: PXVX0200
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand the study and give written consent. Healthy male and female adults, age 46-64 years (inclusive) without significant medical history, physical, or abnormal screening laboratory test results at screening. 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. Willing and able to comply with the study requirements and procedures. Exclusion Criteria: 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. Abnormal stool pattern defined as fewer than 3 stools per week or more than 2 stools per day in past 6 months. Regular use of laxatives in the past 6 months. Previously received a licensed or investigational cholera vaccine. History of cholera or enterotoxigenic E. coli infection (natural infection or experimental challenge). Travel to a cholera-endemic area in the previous 5 years. 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. Received or plans to receive antibiotics or chloroquine within 14 days prior to the study vaccination through to 29 days after vaccination. Recipient of bone marrow or solid organ transplant. Use of systemic chemotherapy in the previous 5 years prior to the study. Malignancy (excluding non-melanotic skin cancers) or lymphoproliferative disorders diagnosed or treated during the past 5 years. 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. History of Guillain-Barré Syndrome. Pregnant or nursing.

Ages Eligible for Study
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Minimum Age: 46 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PXVX0200 in Older Adults<br>PXVX0200 Single dose; liquid suspension after reconstitution with buffer; > 2x10^8 CFU in a liquid suspension | Biological: PXVX0200<br> <br> |
| Placebo Comparator: Placebo in Older Adults<br>Placebo physiological saline | Biological: Placebo<br> <br> |
| Other: Historical Control: Adults Aged 18-45<br>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<br> <br> |

What is the study measuring?
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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 |