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

Cholera Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02094586
• Other study ID #: PXVX-VC-200-004
• Status: Completed
• Phase: Phase 3
• Start date: May 2014
• Est. completion date: June 2015

Study information

• Verified date: June 2023
• Source: Bavarian Nordic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3146
• Est. completion date: June 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Cholera

Intervention

Biological:
• PXVX0200 Lot A
Lot P700-1CA03
• PXVX0200 Lot B
Lot P700-3CA03
• PXVX0200 Lot C
Lot P700-6BA03
• Placebo
Placebo

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Bavarian Nordic	Emergent BioSolutions

Countries where clinical trial is conducted

United States,  Australia, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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