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

Phase 3

Completed

Conditions: Cholera

Interventions: Biological: PXVX0200 Lot B
Biological: Placebo
Biological: PXVX0200 Lot A
Biological: PXVX0200 Lot C

Registration Number: NCT02094586

Lead Sponsor: Bavarian Nordic

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

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 3146

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PXVX0200 Lot B	PXVX0200 Lot B	PXVX0200 (Lot P700-3CA03) Single dose; liquid suspension after reconstitution with buffer; \> 2x10\^8 CFU in a liquid suspension
Placebo	Placebo	Placebo physiological saline
PXVX0200 Lot A	PXVX0200 Lot A	PXVX0200 (Lot P700-1CA03) Single dose; liquid suspension after reconstitution with buffer; \> 2x10\^8 CFU in a liquid suspension
PXVX0200 Lot C	PXVX0200 Lot C	PXVX0200 (Lot P700-6BA03) Single dose; liquid suspension after reconstitution with buffer; \> 2x10\^8 CFU in a liquid suspension

Primary Outcome Measures

Name	Time	Method
Geometric Mean Ratio (GMR) at Day 11 for Vaccine Lots A and B	Day 11	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.
Geometric Mean Ratio (GMR) at Day 11 for Vaccine Lots B and C	Day 11	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.
Geometric Mean Ratio (GMR) at Day 11 for Vaccine Lots A and C	Day 11	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.

Secondary Outcome Measures

Name	Time	Method
SVA and Anti-CT IgG GMT at Day 1, 11, 29, 91 and 181	Day 1 - 181	GMTs of vibriocidal antibody and anti-CT IgG concentrations at Days 1, 11, 29, 91, and 181.
SVA and Anti-CT IgG Seroconversion at Day 1, 11, 29, 91 & 181	Day 1 - 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.
Adverse Events	Day 1 - 29	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.
SVA Seroconversion at Day 11	Day 11	Percentage of subjects who demonstrated a ≥4-fold rise over baseline in serum vibriocidal antibody (SVA) at Day 11

Trial Locations

Locations (25): Miami Research Associates
🇺🇸
Miami, Florida, United States
Central Kentucky Research
🇺🇸
Lexington, Kentucky, United States
Linear Clinical Research
🇦🇺
Nedlands, Western Australia, Australia
Johnson County Clin-Trials
🇺🇸
Lenexa, Kansas, United States
Coastal Clinical Research
🇺🇸
Mobile, Alabama, United States
Boston University
🇺🇸
Boston, Massachusetts, United States
Center for Pharmaceutical Research
🇺🇸
Kansas City, Missouri, United States
Avail Clinical Research
🇺🇸
DeLand, Florida, United States
Clinical Reseach Consortium Arizona
🇺🇸
Phoenix, Arizona, United States
Emory University
🇺🇸
Atlanta, Georgia, United States
Heartland Research Associates
🇺🇸
Wichita, Kansas, United States
University of Kentucky
🇺🇸
Lexington, Kentucky, United States
Lion Research
🇺🇸
Norman, Oklahoma, United States
Clinical Research Consortium Las Vegas
🇺🇸
Las Vegas, Nevada, United States
Rochester Clinical Research
🇺🇸
Rochester, New York, United States
St. Louis University
🇺🇸
Saint Louis, Missouri, United States
Coastal Carolina Research
🇺🇸
Mount Pleasant, South Carolina, United States
Jean Brown Research
🇺🇸
Salt Lake City, Utah, United States
Research Across America
🇺🇸
Dallas, Texas, United States
AUS Trials Pty Ltd
🇦🇺
Sherwood, Queensland, Australia
QIMR Berghofer Medical Research Institiue
🇦🇺
Herston, Queensland, Australia
CMAX
🇦🇺
Adelaide, South Australia, Australia
Nucleus Network
🇦🇺
Melbourne, Victoria, Australia
Emeritis Research
🇦🇺
Malvern East, Victoria, Australia
Palm Beach Research
🇺🇸
West Palm Beach, Florida, United States