Study of Alternative Vaccination Schedule of Oral Cholera Vaccine

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Brief Title

Study of Alternative Vaccination Schedule of Oral Cholera Vaccine

Official Title

A Randomized Controlled Trial To Evaluate the Immunogenicity of Two Doses of the Modified Killed Whole-Cell Oral Cholera Vaccine Under Two Alternative Vaccination Schedules.

Brief Summary

      The absence of a boosting response after a 14 day interval with the two-dose regimen of the
      modified killed oral cholera vaccine raises the possibility that a longer dosing interval may
      be required to observe a boost in the immune response. This study will compare the immune
      responses following 14-day and 28-day dosing intervals.
    

Detailed Description

      Cholera is a re-emerging infectious disease that causes significant morbidity and mortality
      in populations lacking access to safe drinking water and sanitation. Provision of safe
      drinking water and food, establishment of adequate sanitation, and implementation of personal
      and community hygiene constitute the main public health interventions against cholera. These
      measures cannot be implemented fully in the near future in most cholera-endemic areas.
      Improvements to water and sanitation require substantial long-term investments, commitment
      from the local government and often take years to implement. In the meantime, a safe,
      effective, and affordable vaccine would be a useful tool for cholera prevention and control.

      Considerable progress has been made during the last decade in the development of new
      generation oral cholera vaccines against cholera. A monovalent (anti-O1) WC-rBS oral killed
      cholera vaccine with a B-subunit was developed by Professor Jan Holmgren in Sweden and is
      sold primarily as a traveler's vaccine; and is only WHO pre-qualified vaccine till date. A
      version of this vaccine that lacks the B subunit and is considerably less expensive to
      produce ("whole-cell only") and which is now bivalent (O1 and O139), has been produced and
      used exclusively in Vietnam, making it the first oral cholera vaccine used primarily for
      endemic populations.

      To internationalize the use of this improved vaccine, its production technology was modified
      to comply with the WHO Manufacturing practices (cGMP) standards before its manufacturing
      technology was transferred to an Indian manufacturing company Shantha Biotechnics Limited by
      the International Vaccine Institute. The modified killed bivalent oral cholera vaccine has
      been recently licensed by the Drugs Controller General of India (DCGI) to the Shantha
      Biotechnics Limited and being marketed as Shancol ® after phase II and Phase III clinical
      trials. It is administered orally in 2 liquid doses (without need of any buffer solution) 14
      days for individuals aged 1 year and above. It was found safe, effective and provided 67%
      protection after two years in a placebo-controlled, randomized trial in Kolkata, India.

      Despite the recent licensure, there are remaining questions that need to be answered that
      would be vital in deploying the vaccine including optimization of dosing regimen. A previous
      study performed in Kolkata revealed that two doses of the vaccine when given 14 days apart
      did not result in higher immune response after the first dose, contrary to earlier findings
      with the Swedish vaccine. This new finding may be due to the higher lipopolysaccharide (LPS)
      content of the modified vaccine which may have elicited sufficient immune response that it
      effectively blocks subsequent antigen presentation with the second dose of the vaccine.

      In order to assess if immune responses will be boosted if we prolong the interval between
      dosing of the modified killed oral cholera vaccine, a Phase II double-blind, controlled,
      randomized trial to evaluate two different dosing interval schedules for the two-dose regimen
      will be conducted. This study will compare the immune responses following 14-day and 28-day
      dosing intervals. In addition to the 356 subjects for the main study, 30 subjects will be
      enrolled to explore the possibility of any other immunological marker for vibrio cholera
      infection.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Proportion of subjects exhibiting 4-fold or greater rises in titers of serum vibriocidal antibodies, relative to baseline, 14 days after last dose of study agent in each dose-interval group

Secondary Outcome

 Proportion of subjects exhibiting 4-fold or greater rises in titers of serum vibriocidal antibodies, relative to baseline, 14 days after first dose of study agent

Condition

Cholera

Intervention

Modified killed oral cholera vaccine at 14 day interval

Study Arms / Comparison Groups

 Arm 1: Adults; 14 days interval
Description:  89 Adults (=> 18 years aged) receiving study agents (Vaccine/Placebo) at 14 days inter-dose interval

Publications

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

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

386

Start Date

December 2010

Completion Date

February 2013

Primary Completion Date

February 2013

Eligibility Criteria

        Healthy, non-pregnant adults aged 18 years and above and healthy children aged 1 - 17 will
        be recruited in Kolkata.

        Inclusion Criteria:

          -  Males or non-pregnant females aged 18 years and above and children aged 1 -17 years
             who the investigator believes will comply with the requirements of the protocol (i.e.
             available for follow-up visits and specimen collection).

          -  Written informed consent obtained from the subjects or their parents/guardians, and
             written assent for children aged 12 - 17 years.

          -  Healthy subjects as determined by:

               -  Medical history

               -  Physical examination

               -  Clinical judgment of the investigator

        Exclusion Criteria:

          -  Ongoing serious chronic disease

          -  For females of reproductive age: Pregnancy (or females planning to become pregnant
             during the study period; as determined by verbal screening)

          -  Immunocompromising condition or therapy (for corticosteroids this would mean ≥0.5
             mg/kg/day)

          -  Diarrhea (3 or more loose/watery stools within a 24-hour period) 6 weeks prior to
             enrollment

          -  One or two episodes of diarrhea lasting for more than 2 weeks in the past 6 months

          -  One or two episodes of abdominal pain lasting for more than 2 weeks in the past 6
             months

          -  Intake of any anti-diarrhea medicine in the past week

          -  Abdominal pain or cramps, loss of appetite, nausea, general ill-feeling or vomiting in
             the past 24 hours

          -  Acute disease one week prior to enrollment, with or without fever. Temperature ≥38ºC
             warrants deferral of the vaccination pending recovery of the subject

          -  Receipt of immunoglobulin or any blood product during the past 3 months

          -  Receipt of antibiotics in past 14 days

          -  Receipt of live or killed enteric vaccine in past 4 weeks

          -  Receipt of killed oral cholera vaccine
      

Gender

All

Ages

1 Year - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Dipika Sur, MD, DPH, , 

Location Countries

India

Location Countries

India

Administrative Informations


NCT ID

NCT01233362

Organization ID

CR-WC-05


Responsible Party

Sponsor

Study Sponsor

International Vaccine Institute

Collaborators

 National Institute of Cholera and Enteric Diseases, India

Study Sponsor

Dipika Sur, MD, DPH, Principal Investigator, National Institute of Cholera and Enteric Diseases, Kolkata, India


Verification Date

August 2012