Safety and Immunogenicity of Locally Manufactured New (HL-OCV) Oral Cholera Vaccine

Brief Title

Safety and Immunogenicity of Locally Manufactured New (HL-OCV) Oral Cholera Vaccine

Official Title

A Phase I/II Dose-escalation Study to Evaluate Safety, Tolerability and Immunogenicity of '2-dose Primary Series' Single Strain (Hikojima Serotype) Inactivated Oral Cholera Vaccine Formulations (Two Formulations Based on Total O1 LPS Content), in Sequential Age Descending Population of Healthy Adults and Children

Brief Summary

      Cholera, a rapidly dehydrating watery diarrheal disease transmitted through water or food
      contaminated with the bacterium, Vibrio cholerae, is a major cause of morbidity and mortality
      in low income countries like Bangladesh. In our country, Cholera disease burden consists of
      both cholera outbreaks and endemic cholera comprising at least 300,000 severe cases and 1.2
      million infections each year. To combat this situation, Vaccination against cholera has been
      proved effective both in endemic and epidemic settings. But, the WHO recommended Dukoral and
      Prequalified Shanchol are quite expensive for our country perspective. Therefore, locally
      manufactured OCV can improve the cost effectiveness and make it affordable for all. The
      hypothesis of this proposal is that Locally produced orally administered whole cell
      inactivated HL-OCV test formulations A and B are safe and immunogenic in adults and children
      in Bangladesh as compared to ShancholTM. The results of the study will allow us to understand
      the safety and immunogenicity outcome of the HL-OCV compared to Shanchol vaccine. The total
      sample size will be 840 healthy participants. 840 healthy participants (360 adults, 240
      Children and Adolescent and 240 young children) of 18-45 years, 5- less than 18 years and 1
      year to less than 5 years will be enrolled in the study. Children whose parents/guardians
      give voluntary consent will be enrolled in the study. The investigators will provide 2 dose
      of vaccine for three groups in 14 days interval. Test formulations will be locally
      manufactured and the comparator group will get Shanchol. The Investigators propose to collect
      three blood samples (Day 0, 14 and 28).
    

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
      settings30. 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 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 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, MSD Wellcome Trust Hilleman
      Labs. Pvt. Ltd in collaboration with Goteberg University, Sweden has engineered new oral
      cholera vaccine HL-OCV,consisting of formaldehyde-inactivated recombinant V.cholerae strain
      ,MS 1568 expressing both Ogawa and Inaba antigens. The vaccine formulation is quantified on
      total O1 lipopolysaccharide ,LPS content which is matched to that of ShancholTM ,not less
      than 600 mcg/ml LPS for O1; Formulation A and higher than Shanchol ,not less than 900 mcg/ml
      LPS for O1; Formulation B. The vaccine technology is transferred to local manufacturer
      ,INCEPTA in Bangladesh.

      Relevance: The study of this locally manufactured new HL-OCV, among children and adults will
      be able to give us information regarding the safety and immunogenicity of two different
      formulations of vaccine, based on LPS content. The study will not only identify safe
      formulation among the two formulation A or B, but will also be able to show superiority of
      higher LPS formulation in most naive population in children who are 1-5 years of age. Results
      of the study will be able to identify and select most suitable formulation in Phase II study
      for licensure in Bangladesh. This study will further pave the way forward for field studies
      which could establish field efficacy of vaccine compared to existing vaccines in Bangladesh.

      Hypothesis : Locally produced orally administered whole cell inactivated HL-OCV test
      formulations A and B are safe and immunogenic in adults and children in Bangladesh as
      compared to Shanchol TM.

      Objectives: The objective of this study is to determine most safe and immunogenic formulation
      for new oral cholera vaccine HL-OCV, and comparing with licensed vaccine ShancholTM.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

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

Secondary Outcome

 Number of participant showing seroconversion of vibriocidal antibody against serogroup O1 Inaba

Condition

Cholera

Intervention

HL-OCV

Study Arms / Comparison Groups

 HL-OCV

Description:  Pharmaceutical company in Bangladesh is now producing HL-OCV, with technological support from MSD wellcome trust Hilleman pt. ltd, which meets international Good manufacturing practice( GMP) standards and WHO production guidelines.

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

840

Start Date

July 2016

Completion Date

November 2017

Primary Completion Date

November 2017

Eligibility Criteria

        Inclusion Criteria:

          1. Age: 1years to less than 5 years for the younger children group; 5- less than18 years
             for older children and adolescent group and 18- 45 years (inclusive) for the adult
             group.

          2. Sex: Male, Female, Transgender.

          3. Consent: Informed consent from study participants and guardian in case of children
             along with assent in children 11-17 years (inclusive) of age.

          4. Apparently healthy.

        Exclusion Criteria:

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

          2. History of taking oral cholera vaccine.

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

          7. Currently on antimicrobial therapy (taking antibiotics within 24 hours during
             screening and vaccination).

          8. Severe malnutrition defined as wt-for-ht z-score <-3.0 with or without oedema.

          9. For married females pregnancy or plans to become pregnant during the study period (as
             determined by verbal screening) will be excluded. In addition, pregnancy test will be
             done by pregnancy strip test before each day of vaccination (Day 0 and day 14) for
             married female.

         10. Culture positive V. cholerae, ETEC, Salmonella and Shigella in stool.
      

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

NCT02823899

Organization ID

PR-16021

Responsible Party

Sponsor

Study Sponsor

International Centre for Diarrhoeal Disease Research, Bangladesh

Collaborators

 MSD Wellcome Trust Hilleman Laboratories Pvt. Ltd.

Study Sponsor

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

Verification Date

January 2017