Safety and Immunogenicity of Locally Manufactured Oral Cholera Vaccine
Safety and Immunogenicity of Locally Manufactured Oral Cholera Vaccine
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).
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.
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 .