Safety and Immunogenicity of Locally Manufactured Oral Cholera Vaccine

Brief Title

Safety and Immunogenicity of Locally Manufactured Oral Cholera Vaccine

Official Title

A Randomized Observer Blinded Controlled Non Inferiority Trial to Evaluate the Safety and Immunogenicity of Locally Manufactured Inactivated Bivalent Whole Cell-oral Cholera Vaccine (WC-OCV) 'Cholvax' in Bangladeshi Healthy Adults and Children

Brief Summary

      To evaluate and compare the safety and immunogenicity of the Cholvax with ShancholTM,
      Investigators will conduct a clinical trial study Bangladeshi healthy adults and children.
      Cholvax is locally produced orally administered whole cell inactivated bivalent cholera
      vaccine. Incepta vaccine Limited, a leading pharmaceutical company in Bangladesh is now
      producing the oral cholera vaccine, Cholvax with technological support from International
      Vaccine Institute (IVI). Cholvax meets international Good Manufacturing Practice (GMP)
      standards and WHO production guidelines. Cholvax has the same formulation as ShancholTM in
      terms of strains and formulation. By this transfer of technology, it expected that the
      vaccine will become available for use in public health programs in Bangladesh and in the
      future in other cholera-affected countries in Asia and Africa to control endemic cholera, as
      well as to help control large-scale epidemics and outbreaks.

      Investigators will also evaluate and compare the safety and immunogenicity of 3 Cholvax lots
      (lot-to-lot consistency).
    

Detailed Description

      Background : Cholera continues to be a major cause of morbidity and mortality in low-income
      countries including Bangladesh. It is estimated that there are at least 300,000 severe cases
      and over 4,500 deaths in Bangladesh each year1. The overall morbidity for cholera remains
      high. A global stockpile of OCV has been created by WHO in 2013 for epidemic and outbreak
      settings2. However, the global demand for the vaccine far exceeds the present supply for both
      epidemic and also endemic settings3. It can be envisioned that local production of an
      affordable OCV for high risk population in endemic settings will improve the present scenario
      in Bangladesh and other countries.

      Knowledge gap: The WHO recommends OCV for use in both endemic and epidemic cholera settings4.
      At present there are two vaccines that are WHO prequalified. These include Dukoral which is
      registered in Bangladesh and in over 50 countries. However, the disadvantage of use of
      Dukoral is that its current price it is expensive for Bangladesh and other developing
      countries. In addition, the need for buffer to formulate the vaccine makes it less fieldable
      for mass vaccination programs. Another whole cell killed OCV, ShancholTM, which is WHO
      prequalified, is based on similar bacterial components as Dukoral and licensed in India but
      not in Bangladesh. Although this vaccine is relatively affordable it may not be sufficiently
      cost effective for the Government of Bangladesh to implement it in our poor endemic settings.
      At present, the vaccine is in short supply and will not be able to meet the global demands.
      In order to increase supply of OCV and make the vaccine more affordable, a locally
      manufactured killed bivalent whole cell-oral cholera vaccine Cholvax is now available. The
      present study will evaluate the safety and immunogenicity of Cholvax as a test vaccine using
      Shanchol TM as the comparator vaccine in a non inferiority trial design.

      Relevance: The study of this locally manufactured OCV, Cholvax among children and adults will
      be able to give us information regarding the safety and immunogenicity of the vaccine. Based
      on this information, it can be anticipated that regulatory requirements as well as licensure
      of the vaccine will be initiated in Bangladesh. This will pave the way forward for the future
      approval by WHO and for its global use. The introduction of Cholvax in endemic settings,
      seasonal outbreak as well as in the EPI program of the country in the future can be expected
      based on the study results; initiatives and plans can be made to introduce this locally
      produced vaccine in Bangladesh at an affordable cost and in the future globally.

      Hypothesis (if any): Locally produced orally administered whole cell inactivated bivalent
      cholera vaccine, Cholvax is non inferior or at least as safe and immunogenic in adults and
      children in Bangladesh as compared to Shanchol TM.

      Objectives: The objectives of this study are- i. To evaluate and compare the safety and
      immunogenicity of the Cholvax with ShancholTM ii. To evaluate the safety and immunogenicity
      of Cholvax in healthy adults and children in Dhaka.

      iii. To evaluate and compare the safety and immunogenicity of 3 Cholvax lots (lot-to-lot
      consistency) Methods: This will be a randomized, observer blinded and comparative study on a
      total of 2052 healthy participants, 1026 Cholvax (Test Group) and 1026 ShancholTM (Comparator
      Group) recipients. There will be three age cohort arms in each test and comparator group
      which will consist of 219 participants for age 1-5Yrs, 373 participants for age 6-17Yrs and
      434 for Age 18-45Yrs, with a total of 2052 participants. Participants will receive either
      Cholvax or ShancholTM two doses 14 days apart.

      Each age cohort of the study (Cohort I onwards) will be completed and based on the
      development, and progress, the next age cohort will be initiated. If the vaccine is found to
      be safe in the adults it will be tested in the children, 6-17 years of age and followed by
      the younger age group 1-5 years of age. The results will be presented to the Data Safety
      Monitoring Board after completing the 28-day safety surveillance part of each age cohort of
      the study and before proceeding to the next study age cohort.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Number of participants with vaccine related reactogenicity as assessed by study personnel

Secondary Outcome

 Number of participants showing seroconversion against sero group V. cholerae O139

Condition

Cholera

Intervention

Cholvax

Study Arms / Comparison Groups

 cholvax

Description:  Incepta vaccine Limited, a leading pharmaceutical company in Bangladesh is now producing the OCV, Cholvax with technological support from International Vaccine Institute (IVI), which meets international Good Manufacturing Practice (GMP) standards and WHO production guidelines. Cholvax has the same formulation as ShancholTM in terms of strains and formulation.

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

2052

Start Date

April 2016

Completion Date

June 2017

Primary Completion Date

June 2017

Eligibility Criteria

        Inclusion Criteria:

          1. Age: 1-45 Years.

          2. Informed consent from study participants and guardian in case of children (1-17 years)
             and assent from children aged 11-17 years.

          3. Participation in the study at least for next 6 months

          4. Considered healthy as per medical judgment of the investigator

        Exclusion Criteria:

          1. Suffering from diarrhea or abdominal pain or vomiting in the past 24 hours or diarrhea
             lasting for more than 2 weeks in the past 6 months

          2. History of taking oral cholera vaccine and history of confirmed cholera.

          3. History of taking any other live or killed enteric vaccine in the last 8 weeks.

          4. History of anaphylaxis or serious vaccine reaction.

          5. Currently use of any immunosuppressive or immune-modifying drugs. 6.100.4 0 F (38℃) or
             higher body temperature measured prior to investigational product dosing.

        7.Receipt of blood or blood products or parenteral immunoglobulin preparation in the past 3
        months.

        8.Currently on antimicrobial therapy. 9.Severe malnutrition or chornic disease based on the
        jugement of the investigator.

        10.Stool sample at screening positive for V. cholerae. 11.Pregnant women or plans to become
        pregnant during the study period .
      

Gender

All

Ages

1 Year - 45 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Firdausi Qadri, Dr., , 

Location Countries

Bangladesh

Location Countries

Bangladesh

NCT ID

NCT02742558

Organization ID

PR-15076

Responsible Party

Sponsor

Study Sponsor

International Centre for Diarrhoeal Disease Research, Bangladesh

Collaborators

 International Vaccine Institute

Study Sponsor

Firdausi Qadri, Dr., Study Director, International Centre for Diiarrhoeal Disease Research, Bangladesh

Verification Date

October 2016