A Study of Live Oral Cholera Vaccine, PXVX200 in Healthy... | NCT02100631

Status Module

Name	Class
Emergent BioSolutions	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
PXVX0200 in Older Adults	Experimental	PXVX0200 Single dose; liquid suspension after reconstitution with buffer; > 2x10^8 CFU in a liquid suspension	Biological: PXVX0200
Placebo in Older Adults	Placebo Comparator	Placebo physiological saline	Biological: Placebo
Historical Control: Adults Aged 18-45	Other	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

Name	Type	Description	Arm Group Labels	Other Names
PXVX0200	Biological		Historical Control: Adults Aged 18-45 PXVX0200 in Older Adults
Placebo

Outcomes Module

Primary Outcomes

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

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

Other Outcomes

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

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
James McCarty, MD	Emergent Travel Health Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Coastal Clinical Research		Mobile	Alabama	36608	United States
Avail Clinical

PubMed Identifier	Type	Citation	Retractions
30772070	Result	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.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	PXVX0200 in Older Adults	PXVX0200 Single dose; liquid suspension after reconstitution with buffer; > 1x10^9 CFU in a liquid suspension
FG001	Placebo in Older Adults	Placebo physiological saline

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	PXVX0200 in Older Adults	PXVX0200 is a live-attenuated cholera vaccine for single-dose oral administration. Subjects will be randomly assigned 3:1 to receive PXVX0200 (300) or placebo (100). Each subject will have at least 4 visits composed of a screening visit, a vaccination visit (Day 1), and post-vaccination visits at Day 11, and Day 29 telephone contacts will be made on Day 91 and 181.
BG001	Placebo in Older Adults	The placebo consisted of 100 mL of physiological saline administered orally. Physiological saline was sourced by the clinical sites. Subjects will be randomly assigned 3:1 to receive PXVX0200 (300) or placebo (100). Each subject will have at least 4 visits composed of a screening visit, a vaccination visit (Day 1), and post-vaccination visits at Day 11, and Day 29 telephone contacts will be made on Day 91 and 181.
BG002	Historical Control: Adults Aged 18-45	This arm consists of historical data from Vaxchora vaccine subjects from 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
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG000299 BG00199 BG0022688 BG0033086

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Between 46-64 years (inclusive)

Title	Measurements
<=18 years	BG0000 BG0010 BG0020 BG003

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00053.8± 4.99 BG00154.1± 5.20 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000164 BG00152 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0006 BG0011 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG000299 BG00199 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Immunogenicity Evaluable Population (IEP)

Posted

Number

95% Confidence Interval

% of participants

Day 11

ID	Title	Description
OG000	PXVX0200 in Older Adults	PXVX0200 is a live-attenuated cholera vaccine for single-dose oral administration. Subjects will be randomly assigned 3:1 to receive PXVX0200 (300) or placebo (100). Each subject will have at least 4 visits composed of a screening visit, a vaccination visit (Day 1), and post-vaccination visits at Day 11, and Day 29 telephone contacts will be made on Day 91 and 181.
OG001	Historical Control: Adults Aged 18-45	This arm consists of historical data from Vaxchora vaccine subjects from 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

Units	Counts
Participants	OG000291 OG0012687

Title

Denominators

Categories

Title	Measurements
	OG00090.4(86.4 to 93.5) OG00193.5(92.5 to 94.4)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Risk Difference (RD)	-3.1			2-Sided	95	-6.7	0.4					Non-Inferiority	The lower limit of the two sided 95% Wald CI on the difference in seroconversion rate was estimated by inverting a Z test with pooled variance. The lower limit of the CI had be greater than -10 percentage points to prove non-inferiority. The lower bound of the CI on the older adults serconversion rate was required to exceed 70%.

Secondary

Geometric Mean Titer (GMT)

The Day 11 vibriocidal GMTs were compared between older and younger adults.

IEP

Posted

Mean

95% Confidence Interval

Geometric Mean Titer

Day 11

ID	Title	Description
OG000	PXVX0200 in Older Adults	PXVX0200 is a live-attenuated cholera vaccine for single-dose oral administration. Subjects will be randomly assigned 3:1 to receive PXVX0200 (300) or placebo (100). Each subject will have at least 4 visits composed of a screening visit, a vaccination visit (Day 1), and post-vaccination visits at Day 11, and Day 29 telephone contacts will be made on Day 91 and 181.
OG001	Historical Control: Adults Aged 18-45	This arm consists of historical data from Vaxchora vaccine subjects from 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
OG002	Placebo in Older Adults	Placebo physiological saline

Other Pre-specified

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.

IEP

Posted

Number

95% Confidence Interval

% of participants

Day 29

ID	Title	Description
OG000	PXVX0200 in Older Adults	PXVX0200 is a live-attenuated cholera vaccine for single-dose oral administration. Subjects will be randomly assigned 3:1 to receive PXVX0200 (300) or placebo (100). Each subject will have at least 4 visits composed of a screening visit, a vaccination visit (Day 1), and post-vaccination visits at Day 11, and Day 29 telephone contacts will be made on Day 91 and 181.
OG001	Historical Control: Adults Aged 18-45	This arm consists of historical data from Vaxchora vaccine subjects from 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
OG002	Placebo in Older Adults	Placebo physiological saline

Other Pre-specified

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.

IEP. Placebo was not included in this additional bridging analysis as increase in SVA titer from Day 1 to 11 is not applicable for placebo subjects.

Posted

Mean

95% Confidence Interval

Fold Change in Titer from Day 1

Day 11

ID	Title	Description
OG000	PXVX0200 in Older Adults	PXVX0200 is a live-attenuated cholera vaccine for single-dose oral administration. Subjects will be randomly assigned 3:1 to receive PXVX0200 (300) or placebo (100). Each subject will have at least 4 visits composed of a screening visit, a vaccination visit (Day 1), and post-vaccination visits at Day 11, and Day 29 telephone contacts will be made on Day 91 and 181.
OG001	Historical Control: Adults Aged 18-45	This arm consists of historical data from Vaxchora vaccine subjects from 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

Units

Other Pre-specified

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.

IEP. The Historical Control population is not included as testing against these other biotypes/serotypes was not included in that study.

Posted

Mean

95% Confidence Interval

% of participants

Day 11

ID	Title	Description
OG000	PXVX0200 in Older Adults	PXVX0200 is a live-attenuated cholera vaccine for single-dose oral administration. Subjects will be randomly assigned 3:1 to receive PXVX0200 (300) or placebo (100). Each subject will have at least 4 visits composed of a screening visit, a vaccination visit (Day 1), and post-vaccination visits at Day 11, and Day 29 telephone contacts will be made on Day 91 and 181.
OG001	Placebo in Older Adults	The placebo consisted of 100 mL of physiological saline administered orally. Physiological saline was sourced by the clinical sites. Subjects will be randomly assigned 3:1 to receive PXVX0200 (300) or placebo (100). Each subject will have at least 4 visits composed of a screening visit, a vaccination visit (Day 1), and post-vaccination visits at Day 11, and Day 29 telephone contacts will be made on Day 91 and 181.

Other Pre-specified

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.

Immune Sub-Study Population. The Historical Control population is not included as anti-CT levels were not assessed in that study.

Posted

Mean

95% Confidence Interval

% of participants

Day 11

ID	Title	Description
OG000	PXVX0200 in Older Adults	PXVX0200 is a live-attenuated cholera vaccine for single-dose oral administration. Subjects will be randomly assigned 3:1 to receive PXVX0200 (300) or placebo (100). Each subject will have at least 4 visits composed of a screening visit, a vaccination visit (Day 1), and post-vaccination visits at Day 11, and Day 29 telephone contacts will be made on Day 91 and 181.
OG001	Placebo in Older Adults	The placebo consisted of 100 mL of physiological saline administered orally. Physiological saline was sourced by the clinical sites. Subjects will be randomly assigned 3:1 to receive PXVX0200 (300) or placebo (100). Each subject will have at least 4 visits composed of a screening visit, a vaccination visit (Day 1), and post-vaccination visits at Day 11, and Day 29 telephone contacts will be made on Day 91 and 181.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	PXVX0200 in Older Adults	PXVX0200 is a live-attenuated cholera vaccine for single-dose oral administration. Subjects will be randomly assigned 3:1 to receive PXVX0200 (300) or placebo (100). Each subject will have at least 4 visits composed of a screening visit, a vaccination visit (Day 1), and post-vaccination visits at Day 11, and Day 29 telephone contacts will be made on Day 91 and 181.	0	296	3	296	37	296
EG001	Placebo in Older Adults	The placebo consisted of 100 mL of physiological saline administered orally. Physiological saline was sourced by the clinical sites. Subjects will be randomly assigned 3:1 to receive PXVX0200 (300) or placebo (100). Each subject will have at least 4 visits composed of a screening visit, a vaccination visit (Day 1), and post-vaccination visits at Day 11, and Day 29 telephone contacts will be made on Day 91 and 181.	0	99	0	99	11	99

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Fatigue	General disorders	MedDRA (15.0)	Systematic Assessment	EG00011 affected296 at risk EG0013 affected99 at risk
Back Pain	Nervous system disorders	MedDRA (15.0)	Systematic Assessment	EG0006 affected296 at risk EG0012 affected99 at risk
Decreased Appetite	Gastrointestinal disorders	MedDRA (15.0)	Systematic Assessment	EG0005 affected296 at risk EG0010 affected99 at risk
Flatulence	Gastrointestinal disorders	MedDRA (15.0)	Systematic Assessment	EG0003 affected296 at risk EG0012 affected99 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (15.0)	Systematic Assessment	EG0003 affected296 at risk EG0012 affected99 at risk
Headache	Nervous system disorders	MedDRA (15.0)	Systematic Assessment	EG0003 affected296 at risk EG0011 affected99 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (15.0)	Systematic Assessment	EG0003 affected296 at risk EG0011 affected99 at risk
Nausea	Gastrointestinal disorders	MedDRA (15.0)	Systematic Assessment	EG0003 affected296 at risk EG0010 affected99 at risk

ID	Term
D014735	Vibrio Infections
D016905	Gram-Negative Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial Fibrillation	Cardiac disorders	MedDRA (15.0)	Systematic Assessment	EG0001 affected296 at risk EG0010 affected99 at risk
Spinal Compression Fracture	Injury, poisoning and procedural complications	MedDRA (15.0)	Systematic Assessment	EG0001 affected296 at risk EG0010 affected99 at risk
Myocardial Infarction	Cardiac disorders	MedDRA (15.0)	Systematic Assessment	EG0001 affected296 at risk EG0010 affected99 at risk