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Study of Alternative Vaccination Schedule of Oral Cholera Vaccine

Primary Purpose

Cholera, Diarrhoea, Vibrio Infection

Status
Completed
Phase
Phase 2
Locations
India
Study Type
Interventional
Intervention
Modified killed oral cholera vaccine at 14 day interval
Modified killed oral cholera vaccine at 28 day interval
Sponsored by
International Vaccine Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cholera focused on measuring Cholera, Vaccine, Kolkata, West Bengal, India, Immunogenicity, Vaccination Schedules

Eligibility Criteria

1 Year - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • National Institute of Cholera and Enteric Diseases

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

Arm 1: Adults; 14 days interval

Arm 2: Adults; 28 days interval

Arm 3: children; 14 days interval

Arm 4: children; 28 days interval

Arm 5: Adults; 14 days Interval

Arm 6: Adults; 28 days interval

Arm Description

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

89 Adults (=> 18 years aged) receiving study agents (Vaccine/Placebo) at 28 days inter-dose interval

89 children (1-17 years aged) receiving study agents (Vaccine/Placebo) at 14 days inter-dose interval

89 children (1-17 years aged) receiving study agents (Vaccine/Placebo) at 28 days inter-dose interval

15 Adults (=> 18 years aged) receiving study agents (Vaccine/Placebo) at 14 days inter-dose interval

15 Adults (=> 18 years aged) receiving study agents (Vaccine/Placebo) at 28 days inter-dose interval

Outcomes

Primary Outcome Measures

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 Measures

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
Geometric mean serum vibriocidal titers at baseline, 14 days after each dose of the study agent, in each dose-interval group.
Proportion of subjects given 2 doses of study agent given 14 and 28 days apart with adverse events.
Adverse events include: Immediate reactions within 30 minutes after each dose Serious Adverse Events occurring throughout the trial Reactogenicity during three consecutive days following each dose: Headache, vomiting, nausea, abdominal pain/cramps, gas, diarrhea, fever,loss of appetite, general ill feeling i. Diarrhea is defined as having 3 or more loose/watery stools within a 24 hour period. ii. Fever is defined as having an oral or tympanic temperature of ≥38o C
Proportion of subjects given 2 doses of vaccine given 14 and 28 days apart with significant immunological responses to the alternate assays under exploration
Immunological responses to: Responses to: Fecal antibody to LPS OMP micro ELISPOT LPS-specific micro ELISPOT IgA to LPS (by ELISA) ALS assay

Full Information

First Posted
October 11, 2010
Last Updated
September 24, 2013
Sponsor
International Vaccine Institute
Collaborators
National Institute of Cholera and Enteric Diseases, India, Indian Council of Medical Research, Shantha Biotechnics Limited
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1. Study Identification

Unique Protocol Identification Number
NCT01233362
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.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2012
Overall Recruitment Status
Completed
Study Start Date
December 2010 (undefined)
Primary Completion Date
February 2013 (Actual)
Study Completion Date
February 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
International Vaccine Institute
Collaborators
National Institute of Cholera and Enteric Diseases, India, Indian Council of Medical Research, Shantha Biotechnics Limited

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cholera, Diarrhoea, Vibrio Infection
Keywords
Cholera, Vaccine, Kolkata, West Bengal, India, Immunogenicity, Vaccination Schedules

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
386 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: Adults; 14 days interval
Arm Type
Active Comparator
Arm Description
89 Adults (=> 18 years aged) receiving study agents (Vaccine/Placebo) at 14 days inter-dose interval
Arm Title
Arm 2: Adults; 28 days interval
Arm Type
Active Comparator
Arm Description
89 Adults (=> 18 years aged) receiving study agents (Vaccine/Placebo) at 28 days inter-dose interval
Arm Title
Arm 3: children; 14 days interval
Arm Type
Active Comparator
Arm Description
89 children (1-17 years aged) receiving study agents (Vaccine/Placebo) at 14 days inter-dose interval
Arm Title
Arm 4: children; 28 days interval
Arm Type
Active Comparator
Arm Description
89 children (1-17 years aged) receiving study agents (Vaccine/Placebo) at 28 days inter-dose interval
Arm Title
Arm 5: Adults; 14 days Interval
Arm Type
Active Comparator
Arm Description
15 Adults (=> 18 years aged) receiving study agents (Vaccine/Placebo) at 14 days inter-dose interval
Arm Title
Arm 6: Adults; 28 days interval
Arm Type
Active Comparator
Arm Description
15 Adults (=> 18 years aged) receiving study agents (Vaccine/Placebo) at 28 days inter-dose interval
Intervention Type
Biological
Intervention Name(s)
Modified killed oral cholera vaccine at 14 day interval
Other Intervention Name(s)
Shancol
Intervention Description
The modified killed bivalent (O1 and O139)whole cell based oral cholera vaccine is administered orally in 2 liquid doses (without need of any buffer solution) 14 days for individuals aged 1 year and above.
Intervention Type
Biological
Intervention Name(s)
Modified killed oral cholera vaccine at 28 day interval
Other Intervention Name(s)
Shancol
Intervention Description
The modified killed bivalent (O1 and O139)whole cell based oral cholera vaccine is administered orally in 2 liquid doses (without need of any buffer solution) 28 days for individuals aged 1 year and above; as an alternate schedule.
Primary Outcome Measure Information:
Title
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
Time Frame
14 days after the last dose of the study agent
Secondary Outcome Measure Information:
Title
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
Time Frame
14 days after first dose of study agent
Title
Geometric mean serum vibriocidal titers at baseline, 14 days after each dose of the study agent, in each dose-interval group.
Time Frame
14 days after each dose of study agent
Title
Proportion of subjects given 2 doses of study agent given 14 and 28 days apart with adverse events.
Description
Adverse events include: Immediate reactions within 30 minutes after each dose Serious Adverse Events occurring throughout the trial Reactogenicity during three consecutive days following each dose: Headache, vomiting, nausea, abdominal pain/cramps, gas, diarrhea, fever,loss of appetite, general ill feeling i. Diarrhea is defined as having 3 or more loose/watery stools within a 24 hour period. ii. Fever is defined as having an oral or tympanic temperature of ≥38o C
Time Frame
upto 1.5 months after the first dose of study agent
Title
Proportion of subjects given 2 doses of vaccine given 14 and 28 days apart with significant immunological responses to the alternate assays under exploration
Description
Immunological responses to: Responses to: Fecal antibody to LPS OMP micro ELISPOT LPS-specific micro ELISPOT IgA to LPS (by ELISA) ALS assay
Time Frame
upto 1.5 months after the first dose of study agent

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dipika Sur, MD, DPH
Organizational Affiliation
National Institute of Cholera and Enteric Diseases, Kolkata, India
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institute of Cholera and Enteric Diseases
City
Kolkata
State/Province
West Bengal
ZIP/Postal Code
700010
Country
India

12. IPD Sharing Statement

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Study of Alternative Vaccination Schedule of Oral Cholera Vaccine

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