Safety and Immunogenicity of a New Formulation of Euvichol®

Phase 3

• Conditions: Cholera
• Interventions: Biological: Test Oral Cholera Vaccine; Biological: Euvichol®

• Registration Number: NCT02502331
• Lead Sponsor: International Vaccine Institute

Brief Summary

* Number of doses and intervals: Two doses, 2 weeks apart

* Method of administration: Oral administration

* Volume of vaccine to be administered: 1.5 mL/dose

* Observational period: 4 weeks (2 weeks after each dose)

* Number of visits: 3 visits

1. Visit 1: Screening and enrollment (1st dosing)

2. Visit 2: 2nd dosing 2 weeks after 1st dose (14+3 days)

3. Visit 3: 2 weeks after the 2nd dose (28+3 days), end of subject participation. This study will be carried out in healthy adults and children, at two sites, enrollment will be competitive between the sites. Subjects will be stratified according to age into adults (18\~40 years of age) and children (1\~17 years of age). According to the pre-generated randomization list, the participants will be randomized to the test or comparator groups (Visit 1) and will be given either the test vaccine or the comparator vaccine. For immunogenicity assessment, blood sample will be taken at Visit 1 (prior to vaccination), Visit 2 (prior to vaccination), and at the end-of-study Visit (Visit 3). For Safety assessment: the participants will be observed for 30 minutes post vaccination and instructed to record solicited adverse events that occur up to 6 days after vaccination on the participant diary card.

This study is observer-blind: vaccine administrator and vaccine safety evaluator will be two distinct persons to avoid bias of safety assessment. Trial staff other than the vaccine administrator will remain blinded and will not handle the investigational product.

Detailed Description

1. Primary immunogenicity endpoint

* Geometric Mean Titer (GMT) of Vibriocidal antibodies against Inaba serogroup O1 post second dose

* GMTof Vibriocidal antibodies against Ogawa serogroup O1 post second dose

* GMT of Vibriocidal antibodies against serogroup O139 post second dose

2. Secondary immunogenicity endpoints

* Proportion of participants showing seroconversion against Inaba serogroup O1, Ogawa serogroup O1and serogroup O139 post vaccinations

* Seroconversion is defined as 4-fold rise in vibriocidal antibody titer at Visit 3 two weeks after the second dose, compared to baseline titers, measured at Visit 1 prior to vaccination.

Proportion of participants with:

1. Immediate reactions within 30 minutes after each dose of vaccination.

2. Solicited systemic Adverse Events: nausea/vomiting, diarrhea, headache, fatigue, myalgia, fever, and anorexia/loss of appetite within 7 days after each vaccination.

1. Diarrhea is defined as having 3 or more loose/watery stools within a 24-hour period or at least 1 bloody loose stool or any number of loose stools with signs of dehydration.

2. Fever is defined as having an axillary temperature of 38 ℃

3. Unsolicited Adverse Events and Serious Adverse Events occurring 14 days following each vaccination, as reported by participants Measurement of Geometric Mean Titer of vibriocidal antibodies post vaccination, Ratio ofGeometric Mean Titer of vibriocidal antibodies post vaccination of Test vaccine' compared with 'Comparator vaccine'.

Expected outcome: Statistical equivalence of the two vaccines.

Study Timeline

• Study First Submitted: 2015-07-14
• Study First Submitted QC: 2015-07-17
• Study First Posted: 2015-07-20
• Status Verified: 2015-12
• Last Update Submitted: 2015-12-15
• Last Update Posted: 2015-12-17
• Study Start: 2016-03
• Primary Completion: 2016-06
• Study Completion: 2016-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 442

Inclusion Criteria

1. Subject willing to provide written informed consent to study participation voluntarily provided by an individual or his/her legally acceptable representative.
2. Individuals aged 1 - 40 years.
3. An individual who can be followed up during the study period and is capable of complying with the study requirements

Exclusion Criteria

1. Known history of hypersensitivity reactions to other preventive vaccines.
2. Known history of immune function disorders including immunodeficiency diseases, or chronic use of systemic steroids (> 20 mg/day prednisone equivalent for periods exceeding 10 days), cytotoxic drugs or other immunosuppressants.
3. Severe chronic diseases, based on the judgment of the investigator.
4. 38℃ or higher body temperature measured prior to investigational product dosing.
5. Abdominal pain, nausea, vomiting, or decreased appetite within 24 hours prior to study initiation.
6. Diarrhea or administration of antidiarrheal drugs or antibiotics to treat diarrhoea within 1 week prior to study initiation.
7. Diarrhea or abdominal pain lasting 2 weeks or longer within 6 months prior to study initiation.
8. Other vaccination within 1 week prior to study initiation or planned vaccination during the study, except for tetanus toxoid vaccine.
9. Participation in another clinical trial with investigational product dosing within 1 month prior to study initiation.
10. Pregnant or lactating women, women of reproductive age planning pregnancy and/or lactation before the end of the study period.
11. An individual thought to have difficulty participating in the study due to other reasons, based on the judgment of the investigator
12. History of cholera vaccinations or history of cholera.
13. History of alcohol or substance abuse
14. Participant planning to move from the study area before the end of study period.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
study group	Test Oral Cholera Vaccine	Test Oral Cholera Vaccine
comparator group	Euvichol®	Euvichol®

Primary Outcome Measures

Name	Time	Method
Immunogenicity endpoint O139	28 days	GMT of Vibriocidal antibodies against serogroup O139 post second dose
Immunogenicity endpoint for Ogawa O1	28 days	GMTof Vibriocidal antibodies against Ogawa serogroup O1 post second dose
Immunogenicity endpoint for Inaba O1	28 days	Geometric Mean Titer (GMT) of Vibriocidal antibodies against Inaba serogroup O1 post second dose

Secondary Outcome Measures

Name	Time	Method
Proportion of participants showing seroconversion against Inaba serogroup O1, Ogawa serogroup O1and serogroup O139 post vaccinations.	28 days
Seroconversion is defined as 4-fold rise in vibriocidal antibody titer at Visit 3 two weeks after the second dose, compared to baseline titers, measured at Visit 1 prior to vaccination.	28 days