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

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

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

Official Title
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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

Conditions
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Cholera

Intervention / Treatment
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* Biological: PXVX0200 Lot A
* Biological: PXVX0200 Lot B
* Biological: PXVX0200 Lot C
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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 Lot A<br>PXVX0200 (Lot P700-1CA03) Single dose; liquid suspension after reconstitution with buffer; > 2x10^8 CFU in a liquid suspension | Biological: PXVX0200 Lot A<br>* Lot P700-1CA03<br>|
| Experimental: PXVX0200 Lot B<br>PXVX0200 (Lot P700-3CA03) Single dose; liquid suspension after reconstitution with buffer; > 2x10^8 CFU in a liquid suspension | Biological: PXVX0200 Lot B<br>* Lot P700-3CA03<br>|
| Experimental: PXVX0200 Lot C<br>PXVX0200 (Lot P700-6BA03) Single dose; liquid suspension after reconstitution with buffer; > 2x10^8 CFU in a liquid suspension | Biological: PXVX0200 Lot C<br>* Lot P700-6BA03<br>|
| Placebo Comparator: Placebo<br>Placebo physiological saline | Biological: Placebo<br>* Placebo<br>|

What is the study measuring?
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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 |