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