Cholera (Disorder)
Conditions
Brief summary
VAXCHORA (Cholera Vaccine, Live, Oral) is a vaccine indicated for active immunization against disease caused by Vibrio cholerae serogroup O1. VAXCHORA is approved for use in adults 18 through 64 years of age travelling to cholera-affected areas. The primary goals of this Phase 4 study are to evaluate the safety and immunogenicity of a single dose of VAXCHORA (1 x 10e9 cfu/dose) in children ages 2 years to \<18 years of age in developed countries.
Detailed description
This is a randomized, placebo-controlled, double-blind, single-crossover study with three age cohorts and two treatment groups within each cohort.
Interventions
BIOLOGICALVAXCHORA (Cholera Vaccine, Live, Oral)
VAXCHORA (Cholera Vaccine, Live, Oral) is a live, attenuated bacterial vaccine suspension for oral administration containing the V. cholerae strain CVD 103-HgR.
OTHERPlacebo
Placebo control for this study is normal (0.9%) saline.
Sponsors
Emergent BioSolutions
Bavarian Nordic
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The study will be conducted as a double-blind study through 181, where neither the sponsor, the statistical team, study volunteer subjects, nor clinical site personnel (except for the unblinded administration staff) will know subjects' treatment assignment. Once each subject has reached their Day 181 visit they will be individually unblinded.
Intervention model description
This is a randomized, placebo-controlled, double-blind, single-crossover study with three age cohorts and two treatment groups within each cohort. The main study consists of a screening period of 30 days, a treatment period from Day 1 to Day 29, and a follow-up period through Day 181. Cohort 1 has an optional sub-study consisting of a long-term follow-up period through Day 730.
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or Female * Between 2 and \<18 years of age on Day 1 * In general good health * Able and willing to provide informed assent for study participation * Primary caregiver is able and willing to provide informed consent for study participation * (for females of childbearing potential) Using an acceptable method of contraception through Day 29
Exclusion criteria
* Current acute gastrointestinal illness or loose stools within 3 days of Day 1 visit * Current acute febrile illness * History of cholera infection * History of cholera vaccination * History of severe allergic reaction (e.g. anaphylaxis) to any ingredient of VAXCHORA * Congenital or acquired immunodeficiency * Pregnancy (for females of childbearing potential) * Any other condition that, in the opinion of the Investigator, creates an unacceptable risk to the subject * Any other condition that, in the opinion of the Investigator, will interfere with the conduct of the study or the validity of the data * Duration of \>2 weeks of abnormal stool pattern, defined as \<3 stools per week or \>2 stools per day in the past 6 months * Regular use of laxatives in the past 6 months * History of enterotoxigenic E. coli infection * Travel to cholera-endemic area in the previous 5 years * Nursing/Breastfeeding * Received or plans to receive the following from 14 days prior to the study vaccination through 11 days after vaccination: Any other licensed vaccines, antibiotics, or chloroquine * Received or plans to receive any other investigational agent throughout the main study (Day 181)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 3 (2 to <6 Years) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae | Day 11 | The proportion of subjects achieving seroconversion of serum vibriocidal antibody (SVA) against the classical Inaba biotype of V. cholerae at Day 11 following one dose of VAXCHORA, defined as a 4-fold or greater rise over baseline Day 1 SVA titer. |
| Cohort 3 (2-5 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years | 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 pediatric seroconversion rate would be non-inferior to the seroconversion rate at Day 11 in adults between the ages of18 and 45 years. |
| Cohort 2 (6-11 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years | 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 pediatric seroconversion rate would be non-inferior to the seroconversion rate at Day 11 in adults between the ages of 18 and 45 years. |
| Cohort 1 (12-17 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years | 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 pediatric seroconversion rate would be non-inferior to the seroconversion rate at Day 11 in adults between the ages of 18 and 45 years. |
| Cohort 2 (6 to <12 Years) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae | Day 11 | The proportion of subjects achieving seroconversion of serum vibriocidal antibody (SVA) against the classical Inaba biotype of V. cholerae at Day 11 following one dose of VAXCHORA, defined as a 4-fold or greater rise over baseline Day 1 SVA titer. |
| Cohort 1 (12-17 Yrs) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae | Day 11 | The proportion of subjects achieving seroconversion of serum vibriocidal antibody (SVA) against the classical Inaba biotype of V. cholerae at Day 11 following one dose of VAXCHORA, defined as a 4-fold or greater rise over baseline Day 1 SVA titer |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 91 | Day 91 | Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 91 for all subjects |
| Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 365 | Day 365 | Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 365 for all subjects |
| Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 29 | Day 29 | Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 29 for all subjects |
| Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 181 | Day 181 | Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 181 for all subjects |
| Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 547 | Day 547 | Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 547 for all subjects |
| Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 730 | Day 730 | Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 730 for all subjects |
| Cohort 2 (6 to <12 Years) - Seroconversion of SVA - Day 29 | Day 29 | Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 29 for all subjects |
| Cohort 3 (2 to <6 Years) - Seroconversion of SVA - Day 29 | Day 29 | Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 29 for all subjects |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 547 | Day 547 | Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 547 for the subjects in the active treatment group who participate in the substudy. |
| Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 365 | Day 365 | Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 365 for the subjects in the active treatment group who participate in the substudy. |
| Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 181 | Day 181 | Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 181 for the subjects in the active treatment group and the placebo crossover group |
| Safety - Unsolicited Adverse Events | Through Day 29 | Evaluate the safety and tolerability of VAXCHORA by collecting unsolicited adverse events by age cohort and overall through Day 29 |
| Safety - Serious Adverse Events | Through Day 181 | Evaluate the safety and tolerability of VAXCHORA by collecting serious adverse events by age cohort and overall through Day 181 |
| Acceptability | Day 1 | Evaluate the acceptability of VAXCHORA using the percent of subjects in each age cohort able to complete the dosing according to protocol. |
| Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 91 | Day 91 | Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 91 for the subjects in the active treatment group and the placebo crossover group |
| Safety - Solicited Adverse Events | Through Day 8 | Evaluate the safety and tolerability of VAXCHORA by collecting solicited adverse events (abdominal pain, headache, lack of appetite, tiredness, diarrhea, nausea, vomiting and fever) by age cohort and overall through Day 8 |
| Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 1 | Day 1 | Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 1 for the subjects in the active treatment group and the placebo crossover group |
| Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 730 | Day 730 | Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 730 for the subjects in the active treatment group who participate in the substudy. |
Countries
United States
Participant flow
Recruitment details
This study included healthy volunteers (2 - 17 years) who were not previously immunized against cholera. A total of 574 subjects were screened, of which 24 were screen failures. A total of 550 subjects randomized, of which 471 received study treatment and 433 and 73 completed the main study for treatment and placebo, respectively. Recruitment July 2017-July 2018.
Pre-assignment details
This study included healthy volunteers (2 - 17 years) who were not previously immunized against cholera. A total of 574 subjects were screened, of which 24 were screen failures. A total of 550 subjects randomized, of which 471 received study treatment and 506 and 62 completed the main and sub studies, respectively. Recruitment July 2017-July 2018. The historical control subjects are not included in the protocol enrollment number for PXVX-VC-200-006. They are solely a comparator population.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (Active, 12-17 Yrs) Subjects aged 12 - 17 were administered a 100 mL oral dose of Vaxchora vaccine on Day 1, and had study visits on Day 11, 29, 91 and 181. Cohort 1 subjects that continued in the long-term follow-up sub-study had visits on days 365, 547 and 730.
VAXCHORA (Cholera Vaccine, Live, Oral): VAXCHORA (Cholera Vaccine, Live, Oral) is a live, attenuated bacterial vaccine suspension for oral administration containing the V. cholerae strain CVD 103-HgR. | 163 |
| Cohort 1 (Placebo, 12 - 17 Yrs) Subjects aged 12 - 17 were administered a 100 mL oral dose of 0.9% saline on Day 1, and had study visits on Day 11, 29, 91 and 181.
Placebo: Placebo control for this study is normal (0.9%) saline. | 26 |
| Cohort 2 (Active, 6 - 11 Yrs) Subjects aged 6 - 11 were administered a 100 mL oral dose of Vaxchora vaccine on Day 1, and had study visits on Day 11, 29, 91 and 181.
VAXCHORA (Cholera Vaccine, Live, Oral): VAXCHORA (Cholera Vaccine, Live, Oral) is a live, attenuated bacterial vaccine suspension for oral administration containing the V. cholerae strain CVD 103-HgR. | 158 |
| Cohort 2 (Placebo, 6 - 11 Yrs) Subjects aged 6 - 11 were administered a 100 mL oral dose of 0.9% saline on Day 1, and had study visits on Day 11, 29, 91 and 181.
Placebo: Placebo control for this study is normal (0.9%) saline. | 27 |
| Cohort 3 (Active, 2 - 5 Yrs) Subjects aged 2 - 5 were administered a 50 mL oral dose of Vaxchora vaccine on Day 1, and had study visits on Day 11, 29, 91 and 181.
VAXCHORA (Cholera Vaccine, Live, Oral): VAXCHORA (Cholera Vaccine, Live, Oral) is a live, attenuated bacterial vaccine suspension for oral administration containing the V. cholerae strain CVD 103-HgR. | 150 |
| Cohort 3 (Placebo, 2 - 5 Yrs) Subjects aged 2-5 were administered a 50 mL oral dose of 0.9% saline on Day 1, and had study visits on Day 11, 29, 91 and 181.
Placebo: Placebo control for this study is normal (0.9%) saline. | 26 |
| Historical Control: Adult Bridging Population This arm consists of historical data from Vaxchora vaccine subjects from study PXVX-VC-200-004. The data was included in study PXVX-VC-200-006 as a comparator bridging population for the Day 11 seroconversion. NCT02094586, PubMed ID: 29317118 | 2,688 |
| Total | 3,238 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Long-term Follow-up (Day 365-730) | Lost to Follow-up | 9 | 0 | 0 | 0 | 0 | 0 | 0 |
| Long-term Follow-up (Day 365-730) | Subject did not want lab drawn | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Long-term Follow-up (Day 365-730) | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Main Study (Day 1 - 181) | Failed Exl 8 and randomized in error | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Main Study (Day 1 - 181) | Lost to Follow-up | 2 | 1 | 6 | 1 | 13 | 1 | 0 |
| Main Study (Day 1 - 181) | Protocol Violation | 0 | 0 | 1 | 1 | 3 | 0 | 1 |
| Main Study (Day 1 - 181) | Withdrawal by Subject | 4 | 1 | 4 | 1 | 4 | 0 | 0 |
| Placebo Crossover (Day 181-365) | Lost to Follow-up | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 3 (Placebo, 2 - 5 Yrs) | Historical Control: Adult Bridging Population | Total | Cohort 1 (Placebo, 12 - 17 Yrs) | Cohort 2 (Active, 6 - 11 Yrs) | Cohort 2 (Placebo, 6 - 11 Yrs) | Cohort 3 (Active, 2 - 5 Yrs) | Cohort 1 (Active, 12-17 Yrs) |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 26 Participants | 0 Participants | 550 Participants | 26 Participants | 158 Participants | 27 Participants | 150 Participants | 163 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 2688 Participants | 2688 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 3.6 years STANDARD_DEVIATION 1.2 | 30.0 years STANDARD_DEVIATION 7.8 | 9.0 years STANDARD_DEVIATION 4.7 | 14.3 years STANDARD_DEVIATION 1.7 | 8.6 years STANDARD_DEVIATION 1.8 | 8.7 years STANDARD_DEVIATION 1.5 | 3.5 years STANDARD_DEVIATION 1.1 | 14.4 years STANDARD_DEVIATION 1.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 11 Participants | 14 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 56 Participants | 61 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 671 Participants | 842 Participants | 4 Participants | 53 Participants | 5 Participants | 67 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 50 Participants | 92 Participants | 0 Participants | 15 Participants | 3 Participants | 11 Participants | 13 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 8 Participants | 8 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 37 Participants | 37 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 1855 Participants | 2184 Participants | 21 Participants | 86 Participants | 18 Participants | 71 Participants | 121 Participants |
| Region of Enrollment Australia | 0 Participants | 347 Participants | 347 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 26 Participants | 2341 Participants | 2891 Participants | 26 Participants | 158 Participants | 27 Participants | 150 Participants | 163 Participants |
| Sex: Female, Male Female | 17 Participants | 1482 Participants | 1746 Participants | 12 Participants | 81 Participants | 10 Participants | 69 Participants | 75 Participants |
| Sex: Female, Male Male | 9 Participants | 1206 Participants | 1492 Participants | 14 Participants | 77 Participants | 17 Participants | 81 Participants | 88 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 165 | 0 / 24 | 0 / 157 | 0 / 25 | 0 / 146 | 0 / 26 |
| other Total, other adverse events | 116 / 165 | 13 / 24 | 93 / 157 | 15 / 25 | 74 / 146 | 12 / 26 |
| serious Total, serious adverse events | 4 / 165 | 0 / 24 | 0 / 157 | 0 / 25 | 0 / 146 | 1 / 26 |
Outcome results
Primary
Cohort 1 (12-17 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years
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 pediatric seroconversion rate would be non-inferior to the seroconversion rate at Day 11 in adults between the ages of 18 and 45 years.
Time frame: Day 11
Population: Immunogenicity Evaluable Population (IEP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Active, 12-17 Yrs) | Cohort 1 (12-17 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years | 99.4 percentage of participants |
| Cohort 1 (Placebo, 12-17 Yrs) | Cohort 1 (12-17 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years | 93.5 percentage of participants |
96.7% CI: [2.4, 7.1]
Primary
Cohort 1 (12-17 Yrs) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae
The proportion of subjects achieving seroconversion of serum vibriocidal antibody (SVA) against the classical Inaba biotype of V. cholerae at Day 11 following one dose of VAXCHORA, defined as a 4-fold or greater rise over baseline Day 1 SVA titer
Time frame: Day 11
Population: Immunogenicity Evaluable Population (IEP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Active, 12-17 Yrs) | Cohort 1 (12-17 Yrs) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae | 99.4 percentage of participants |
| Cohort 1 (Placebo, 12-17 Yrs) | Cohort 1 (12-17 Yrs) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae | 0 percentage of participants |
Primary
Cohort 2 (6-11 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years
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 pediatric seroconversion rate would be non-inferior to the seroconversion rate at Day 11 in adults between the ages of 18 and 45 years.
Time frame: Day 11
Population: Immunogenicity Evaluable Population (IEP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Active, 12-17 Yrs) | Cohort 2 (6-11 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years | 97.8 percentage of participants |
| Cohort 1 (Placebo, 12-17 Yrs) | Cohort 2 (6-11 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years | 93.5 percentage of participants |
96.7% CI: [-0.3, 6.2]
Primary
Cohort 2 (6 to <12 Years) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae
The proportion of subjects achieving seroconversion of serum vibriocidal antibody (SVA) against the classical Inaba biotype of V. cholerae at Day 11 following one dose of VAXCHORA, defined as a 4-fold or greater rise over baseline Day 1 SVA titer.
Time frame: Day 11
Population: Immunogenicity Evaluable Population (IEP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Active, 12-17 Yrs) | Cohort 2 (6 to <12 Years) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae | 97.8 percentage of participants |
| Cohort 1 (Placebo, 12-17 Yrs) | Cohort 2 (6 to <12 Years) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae | 4.2 percentage of participants |
Primary
Cohort 3 (2-5 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years
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 pediatric seroconversion rate would be non-inferior to the seroconversion rate at Day 11 in adults between the ages of18 and 45 years.
Time frame: Day 11
Population: Immunogenicity Evaluable Population (IEP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Active, 12-17 Yrs) | Cohort 3 (2-5 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years | 98.1 percentage of participants |
| Cohort 1 (Placebo, 12-17 Yrs) | Cohort 3 (2-5 Yrs) Primary Endpoint - Non-inferiority of Seroconversion Rate at Day 11 Relative to Adults Aged 18 - 45 Years | 93.5 percentage of participants |
96.7% CI: [-1.1, 6.4]
Primary
Cohort 3 (2 to <6 Years) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae
The proportion of subjects achieving seroconversion of serum vibriocidal antibody (SVA) against the classical Inaba biotype of V. cholerae at Day 11 following one dose of VAXCHORA, defined as a 4-fold or greater rise over baseline Day 1 SVA titer.
Time frame: Day 11
Population: Immunogenicity Evaluable Population (IEP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Active, 12-17 Yrs) | Cohort 3 (2 to <6 Years) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae | 98.1 percentage of participants |
| Cohort 1 (Placebo, 12-17 Yrs) | Cohort 3 (2 to <6 Years) Primary Endpoint - Seroconversion of Serum Vibriocidal Antibody Against V. Cholerae | 0 percentage of participants |
Secondary
Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 181
Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 181 for all subjects
Time frame: Day 181
Population: Immunogenicity Evaluable Population (IEP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Active, 12-17 Yrs) | Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 181 | 73.5 percentage of participants |
| Cohort 1 (Placebo, 12-17 Yrs) | Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 181 | 0 percentage of participants |
p-value: <0.0001Fisher Exact
Secondary
Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 29
Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 29 for all subjects
Time frame: Day 29
Population: Immunogenicity Evaluable Population (IEP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Active, 12-17 Yrs) | Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 29 | 100 percentage of participants |
| Cohort 1 (Placebo, 12-17 Yrs) | Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 29 | 0 percentage of participants |
p-value: <0.0001Fisher Exact
Secondary
Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 365
Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 365 for all subjects
Time frame: Day 365
Population: Immunogenicity Evaluable Population (IEP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Active, 12-17 Yrs) | Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 365 | 68.6 percentage of participants |
Secondary
Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 547
Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 547 for all subjects
Time frame: Day 547
Population: Immunogenicity Evaluable Population (IEP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Active, 12-17 Yrs) | Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 547 | 73.1 percentage of participants |
Secondary
Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 730
Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 730 for all subjects
Time frame: Day 730
Population: Immunogenicity Evaluable Population (IEP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Active, 12-17 Yrs) | Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 730 | 64.5 percentage of participants |
Secondary
Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 91
Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 91 for all subjects
Time frame: Day 91
Population: Immunogenicity Evaluable Population (IEP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Active, 12-17 Yrs) | Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 91 | 85.6 percentage of participants |
| Cohort 1 (Placebo, 12-17 Yrs) | Cohort 1 (12 to <18 Years) - Seroconversion of SVA - Day 91 | 0 percentage of participants |
p-value: <0.0001Fisher Exact
Secondary
Cohort 2 (6 to <12 Years) - Seroconversion of SVA - Day 29
Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 29 for all subjects
Time frame: Day 29
Population: Immunogenicity Evaluable Population (IEP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Active, 12-17 Yrs) | Cohort 2 (6 to <12 Years) - Seroconversion of SVA - Day 29 | 94.9 percentage of participants |
| Cohort 1 (Placebo, 12-17 Yrs) | Cohort 2 (6 to <12 Years) - Seroconversion of SVA - Day 29 | 4.3 percentage of participants |
p-value: <0.0001Fisher Exact
Secondary
Cohort 3 (2 to <6 Years) - Seroconversion of SVA - Day 29
Seroconversion of SVA against the classical Inaba biotype of V. cholerae at Day 29 for all subjects
Time frame: Day 29
Population: Immunogenicity Evaluable Population (IEP)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Active, 12-17 Yrs) | Cohort 3 (2 to <6 Years) - Seroconversion of SVA - Day 29 | 93.9 percentage of participants |
| Cohort 1 (Placebo, 12-17 Yrs) | Cohort 3 (2 to <6 Years) - Seroconversion of SVA - Day 29 | 0 percentage of participants |
p-value: <0.0001Fisher Exact
Other Pre-specified
Acceptability
Evaluate the acceptability of VAXCHORA using the percent of subjects in each age cohort able to complete the dosing according to protocol.
Time frame: Day 1
Population: The data presented is for the population that was randomized and received treatment. For Cohort 2, 2 Vaxchora subjects and 1 placebo subject were randomized, but not treated. For Cohort 3, 4 Vaxchora subjects were randomized, but not treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 (Active, 12-17 Yrs) | Acceptability | 99.4 percent of participants |
| Cohort 1 (Placebo, 12-17 Yrs) | Acceptability | 100 percent of participants |
| Cohort 2 (Active, 6 - 11 Yrs) | Acceptability | 91.0 percent of participants |
| Cohort 2 (Placebo, 6 - 11 Yrs) | Acceptability | 96.2 percent of participants |
| Cohort 3 (Active, 2 - 5 Yrs) | Acceptability | 79.5 percent of participants |
| Cohort 3 (Placebo, 2 - 5 Yrs) | Acceptability | 73.1 percent of participants |
Other Pre-specified
Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 1
Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 1 for the subjects in the active treatment group and the placebo crossover group
Time frame: Day 1
Other Pre-specified
Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 181
Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 181 for the subjects in the active treatment group and the placebo crossover group
Time frame: Day 181
Other Pre-specified
Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 365
Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 365 for the subjects in the active treatment group who participate in the substudy.
Time frame: Day 365
Other Pre-specified
Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 547
Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 547 for the subjects in the active treatment group who participate in the substudy.
Time frame: Day 547
Other Pre-specified
Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 730
Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 730 for the subjects in the active treatment group who participate in the substudy.
Time frame: Day 730
Other Pre-specified
Cohort 1 (12 to <18 Years) Exploratory Endpoint - Anti-O1 Lipopolysaccharide Memory B Cell Concentration at Day 91
Anti-O1 lipopolysaccharide (LPS) memory B cell concentration at Day 91 for the subjects in the active treatment group and the placebo crossover group
Time frame: Day 91
Other Pre-specified
Safety - Serious Adverse Events
Evaluate the safety and tolerability of VAXCHORA by collecting serious adverse events by age cohort and overall through Day 181
Time frame: Through Day 181
Other Pre-specified
Safety - Solicited Adverse Events
Evaluate the safety and tolerability of VAXCHORA by collecting solicited adverse events (abdominal pain, headache, lack of appetite, tiredness, diarrhea, nausea, vomiting and fever) by age cohort and overall through Day 8
Time frame: Through Day 8
Other Pre-specified
Safety - Unsolicited Adverse Events
Evaluate the safety and tolerability of VAXCHORA by collecting unsolicited adverse events by age cohort and overall through Day 29
Time frame: Through Day 29