Safety and Immunogenicity of a New Formulation of Euvichol®

Brief Title

Safety and Immunogenicity of a New Formulation of Euvichol®

Official Title

A Randomized, Observer Blinded, Controlled Trial to Evaluate the Safety and Immunogenicity of a New Formulation of Euvichol® (Killed Bivalent Whole Cell Oral Cholera Vaccine Manufactured by EuBiologics Co. Ltd.) in Healthy Individuals

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 Phase

Phase 3

Study Type

Interventional

Primary Outcome

Immunogenicity endpoint for Inaba O1

Secondary Outcome

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

Condition

Cholera

Intervention

Test Oral Cholera Vaccine

Study Arms / Comparison Groups

 study group

Description:  Test Oral Cholera Vaccine

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Biological

Estimated Enrollment

442

Start Date

March 2016

Completion Date

August 2016

Primary Completion Date

June 2016

Eligibility Criteria

        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.
      

Gender

All

Ages

1 Year - 40 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Laura Digilio, MD, +82-2-881-1363, [email protected]

NCT ID

NCT02502331

Organization ID

IVI-CHOVI-EUVICHOL

Responsible Party

Sponsor

Study Sponsor

International Vaccine Institute

Collaborators

 EuBiologics Co.,Ltd

Study Sponsor

Laura Digilio, MD, Principal Investigator, International Vaccince Institute

Verification Date

December 2015