Safety and Immunogenicity of a Killed Oral Cholera Vaccine in Infants

NCT ID: NCT00548054

Last Updated: 2015-05-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-12-31

Study Completion Date

2016-12-31

Brief Summary

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In order to assess whether the bivalent killed oral cholera vaccine may be used safely among infants who are most at risk for cholera, the investigators need to determine the safety and immunogenicity of the killed oral cholera vaccine among infants less than 1 year of age when given with the expanded program on immunization (EPI) vaccines including diptheria, pertussis and tetanus (DPT), oral polio vaccine (OPV), Hepatitis B vaccines and measles vaccine. Furthermore, the investigators also need to make sure that immune interference does not occur among all the other vaccine antigens given at the same time. Findings from this study will pave the way for the possible use of the killed whole cell oral cholera vaccine (OCV).

Detailed Description

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Cholera is an important public health problem worldwide, remaining endemic in most of the developing world at the same time causing outbreaks in areas where lapses in sanitation occur.

A monovalent (anti-O1) oral killed cholera vaccine with a B-subunit was developed by Professor Jan Holmgren in Sweden and is now licensed to a pharmaceutical company in the United Kingdom. The technology for this vaccine was transferred to Vietnamese scientists at the National Institute of Hygiene and Epidemiology in Hanoi in the mid-1980s.

The Vietnamese developed a bivalent vaccine, with killed 0139 cells and without the B-subunit. Since licensure, more than 9 million doses have been given without any report of serious adverse events.

The vaccine has been reformulated in order to internationalize the vaccine. Phase II trials of this vaccine in Son La, Vietnam and Kolkata, India have found the vaccine to be safe with no serious adverse reactions associated with the vaccine. A phase III study of the reformulated vaccine is ongoing in Kolkata, India.

The youngest person the vaccine has been administered to was a 1 year old. Previous studies with the B-subunit containing killed whole cell vaccine was found to be safe among infants as young as 6 months eliciting significant vibriocidal responses among 53% of vaccinees. However, no data is available regarding the use of the bivalent whole cell killed oral vaccine in infants.

Due to the higher risk of cholera among infants, the possibility of introducing cholera vaccine as part of the expanded programme on immunization (EPI) needs to be investigated.

Data regarding the safety and immunogenicity of the reformulated bivalent killed whole cell vaccine among infants needs to be gathered in order to pave the way for the possible use of this vaccine in cholera-endemic areas where infants and children are most at risk. Furthermore, there is no data regarding the concomitant use of this vaccine with other EPI vaccines given to young infants such as Diphtheria-Tetanus-whole cell Pertussis (DTwP), Oral Polio Vaccine (OPV) Hepatitis B and Measles vaccines. It would be important to determine if interference exists between the killed whole cell vaccine and other antigens included in the regular EPI schedule. Providing the killed whole cell vaccine in the context of the EPI will make it easier to introduce cholera vaccines in areas which are cholera-endemic.

Conditions

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Cholera Diarrhea Vibrio Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Vaccine Group for Vibriocidal Assay

Killed whole cell cholera vaccine bled at day 42 for vibriocidal assay

Group Type EXPERIMENTAL

Bivalent killed oral cholera vaccine

Intervention Type BIOLOGICAL

Oral, 1.5 ml, given 2 times at least 14 days apart

Vaccine Group for EPI Assay

Killed whole cell cholera vaccine bled at day 56 for EPI immunogenicity testing

Group Type EXPERIMENTAL

Bivalent killed oral cholera vaccine

Intervention Type BIOLOGICAL

Oral, 1.5 ml, given 2 times at least 14 days apart

Placebo Group for Vibriocidal Assay

Placebo bled at day 42 for vibriocidal assay

Group Type PLACEBO_COMPARATOR

Killed Escherichia coli K12 placebo

Intervention Type BIOLOGICAL

oral, 1.5 ml per dose

Placebo Group for EPI Assay

Placebo bled at day 56 for EPI immunogenicity testing

Group Type PLACEBO_COMPARATOR

Killed Escherichia coli K12 placebo

Intervention Type BIOLOGICAL

oral, 1.5 ml per dose

Vaccine Group for Vibriocidal and Measles Assay

Killed whole cell cholera vaccine bled at day 14 and 28 for measles immunogenicity testing

Group Type EXPERIMENTAL

Bivalent killed oral cholera vaccine

Intervention Type BIOLOGICAL

Oral, 1.5 ml, given 2 times at least 14 days apart

Placebo Group for Vibriocidal and Measles Assay

Placebo bled at day 14 and 28 for measles immunogenicity testing

Group Type PLACEBO_COMPARATOR

Killed Escherichia coli K12 placebo

Intervention Type BIOLOGICAL

oral, 1.5 ml per dose

Interventions

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Bivalent killed oral cholera vaccine

Oral, 1.5 ml, given 2 times at least 14 days apart

Intervention Type BIOLOGICAL

Killed Escherichia coli K12 placebo

oral, 1.5 ml per dose

Intervention Type BIOLOGICAL

Other Intervention Names

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Shanchol

Eligibility Criteria

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Inclusion Criteria

* Healthy infants aged from birth to 2 months who have not received OPV1, DTP1 or HepB2 will be recruited in Kolkata, North 24 Parganas, and South 24 Parganas
* All subjects must satisfy the following criteria at study entry:

1. Male or female infants aged from birth to 2 months who the investigator believes will comply with the requirements of the protocol (i.e., available for follow-up visits and specimen collection)
2. Written informed consent obtained from their parents/guardians
3. Healthy subjects as determined by:

* Medical history
* Physical examination
* Clinical judgment of the investigator


* Healthy infants aged from 9 months to less than 12 months who have not received measles vaccine will be recruited in Kolkata, North 24 Parganas, and South 24 Parganas
* All subjects must satisfy the following criteria at study entry:

1. Male or female infants aged from 9 months to less than 12 months who the investigator believes will comply with the requirements of the protocol (i.e., available for follow-up visits and specimen collection)
2. Written informed consent obtained from their parents/guardians
3. Healthy subjects as determined by:

* Medical history
* Physical examination
* Clinical judgment of the investigator

Exclusion Criteria

1. Ongoing serious chronic disease
2. Immunocompromising condition or therapy
3. Diarrhea (having more frequent watery stools than usual within a 24 hour period) 6 weeks prior to enrollment
4. Intake of any anti-diarrheal medicine in the past week
5. Irritability, loss of appetite, general ill-feeling or vomiting in the past 24 hours
6. Acute disease one week prior to enrollment, with or without fever. Temperature =\>38C (oral) or axillary temperature =\>37.5C warrants deferral of the vaccination pending recovery of the subject
7. Receipt of antibiotics in past 14 days
8. Receipt of killed oral cholera vaccine
9. Receipt of live or killed enteric vaccine in 2 months
10. Receipt of DTwP1, OPV1 or Hepatitis B2 vaccines
11. One or two episodes of diarrhea lasting for more than 2 weeks in the past 2 months
12. One or two episodes of abdominal pain lasting for more than 2 weeks in the past 2 months
13. Z-score of \< -2 on the weight for age WHO Child Growth Standards


1. Ongoing serious chronic disease
2. Immunocompromising condition or therapy
3. Diarrhea (3 or more loose/watery stools within a 24 hour period) 6 weeks prior to enrollment
4. Intake of any anti-diarrheal medicine in the past week
5. Abdominal pain/cramps, loss of appetite, general ill-feeling or vomiting in the past 24 hours
6. Acute disease one week prior to enrollment, with or without fever. Temperature =\>38C (oral) or axillary temperature =\>37.5C warrants deferral of the vaccination pending recovery of the subject
7. Receipt of antibiotics in past 14 days
8. Receipt of killed oral cholera vaccine
9. Receipt of live or killed enteric vaccine in last 4 weeks
10. Receipt of measles-containing vaccine (MCV)
11. One or two episodes of diarrhea lasting for more than 2 weeks in the past 6 months
12. One or two episodes of abdominal pain lasting for more than 2 weeks in the past 6 months
13. Disease episode potentially related to measles
14. receipt of blood, blood products or a parenteral immunoglobulin preparation in past 3 months
15. History of anaphylaxis, any serious vaccine reaction, allergy to eggs, egg products or to any measles vaccine component
16. Any condition which in the opinion of the investigator might interfere with the evaluation of the study objectives
17. Z-score of \< -2 on the weight for age WHO Child Growth Standards
Minimum Eligible Age

10 Weeks

Maximum Eligible Age

11 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Indian Council of Medical Research

OTHER_GOV

Sponsor Role collaborator

National Institute of Cholera and Enteric Diseases, India

OTHER

Sponsor Role collaborator

Shantha Biotechnics Limited

INDUSTRY

Sponsor Role collaborator

Institute of Child Health

OTHER

Sponsor Role collaborator

International Vaccine Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alok K Deb, PhD, MDDS

Role: PRINCIPAL_INVESTIGATOR

National Institute of Cholera and Enteric Disease

Locations

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National Institute of Cholera and Enteric Disease

Kolkata, West Bengal, India

Site Status

Countries

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India

Central Contacts

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Vijayalaxmi Mogasale, MD

Role: CONTACT

82-2-881-1151

Binod Sah, MBBS, MS

Role: CONTACT

82-2-881-1149

Facility Contacts

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Alok K Deb, PhD, MBBS

Role: primary

91-33-2363-3373

Other Identifiers

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CH-WC-01

Identifier Type: -

Identifier Source: org_study_id

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