Back to resultsSafety and Immunogenicity of a Killed Oral Cholera Vaccine in Infants
Primary Purpose
Cholera, Diarrhea, Vibrio Infections
Status
Unknown status
Phase
Phase 2
Locations
India
Study Type
Interventional
Intervention
Bivalent killed oral cholera vaccine
Killed Escherichia coli K12 placebo
Sponsored by
About this trial
This is an interventional prevention trial for Cholera focused on measuring cholera, vaccine, Kolkata, West Bengal, India, immunogenicity, safety, infants, expanded programme on immunization
Eligibility Criteria
Inclusion Criteria, Infants 10 weeks to 6 months of age at Day 0:
- 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:
- 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)
- Written informed consent obtained from their parents/guardians
Healthy subjects as determined by:
- Medical history
- Physical examination
- Clinical judgment of the investigator
Inclusion Criteria, Infants 9 months to less than 12 months
- 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:
- 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)
- Written informed consent obtained from their parents/guardians
Healthy subjects as determined by:
- Medical history
- Physical examination
- Clinical judgment of the investigator
Exclusion Criteria, Infants 10 weeks to 6 months of age at Day 0:
- Ongoing serious chronic disease
- Immunocompromising condition or therapy
- Diarrhea (having more frequent watery stools than usual within a 24 hour period) 6 weeks prior to enrollment
- Intake of any anti-diarrheal medicine in the past week
- Irritability, loss of appetite, general ill-feeling or vomiting in the past 24 hours
- 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
- Receipt of antibiotics in past 14 days
- Receipt of killed oral cholera vaccine
- Receipt of live or killed enteric vaccine in 2 months
- Receipt of DTwP1, OPV1 or Hepatitis B2 vaccines
- One or two episodes of diarrhea lasting for more than 2 weeks in the past 2 months
- One or two episodes of abdominal pain lasting for more than 2 weeks in the past 2 months
- Z-score of < -2 on the weight for age WHO Child Growth Standards
Exclusion Criteria, Infants 9 months to less than 12 months:
- Ongoing serious chronic disease
- Immunocompromising condition or therapy
- Diarrhea (3 or more loose/watery stools within a 24 hour period) 6 weeks prior to enrollment
- Intake of any anti-diarrheal medicine in the past week
- Abdominal pain/cramps, loss of appetite, general ill-feeling or vomiting in the past 24 hours
- 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
- Receipt of antibiotics in past 14 days
- Receipt of killed oral cholera vaccine
- Receipt of live or killed enteric vaccine in last 4 weeks
- Receipt of measles-containing vaccine (MCV)
- 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
- Disease episode potentially related to measles
- receipt of blood, blood products or a parenteral immunoglobulin preparation in past 3 months
- History of anaphylaxis, any serious vaccine reaction, allergy to eggs, egg products or to any measles vaccine component
- Any condition which in the opinion of the investigator might interfere with the evaluation of the study objectives
- Z-score of < -2 on the weight for age WHO Child Growth Standards
Sites / Locations
- National Institute of Cholera and Enteric Disease
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Placebo Comparator
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
Vaccine Group for Vibriocidal Assay
Vaccine Group for EPI Assay
Placebo Group for Vibriocidal Assay
Placebo Group for EPI Assay
Vaccine Group for Vibriocidal and Measles Assay
Placebo Group for Vibriocidal and Measles Assay
Arm Description
Killed whole cell cholera vaccine bled at day 42 for vibriocidal assay
Killed whole cell cholera vaccine bled at day 56 for EPI immunogenicity testing
Placebo bled at day 42 for vibriocidal assay
Placebo bled at day 56 for EPI immunogenicity testing
Killed whole cell cholera vaccine bled at day 14 and 28 for measles immunogenicity testing
Placebo bled at day 14 and 28 for measles immunogenicity testing
Outcomes
Primary Outcome Measures
Safety: proportion of subjects with diarrhea
Immunogenicity: proportion of subjects exhibiting 4-fold or greater rises in titers of serum vibriocidal antibodies, relative to baseline
Secondary Outcome Measures
Geometric mean serum vibriocidal titers
Proportion of subjects with any of the following: a) immediate reactions 30 minutes and up to 3 days after each dose, b) serious adverse events occurring during the trial, c) any adverse event
Proportion of subjects with ≥ 0.1 mIU/ml of anti-diphtheria toxoid antibodies
Proportion of subjects with ≥ 0.1 mIU/ml of anti-tetanus toxoid antibodies
For initially seronegative subjects: proportion of subjects with ≥ 15 EU/ml of anti-pertussis IgG and for initially seropositive subjects, proportion with antibody titers equal to or greater than the initial titers prior to vaccination
Proportion of subjects with ≥ 10 mIU/ml of anti-HbS antibody
Proportion of subjects with ≥ 8 fold dilution of anti-polio virus 1, 2, or 3 antibodies by micro-neutralization test
Proportion of subjects with >150 mIU/ml measles IgG antibodies
Full Information
NCT ID
NCT00548054
First Posted
October 21, 2007
Last Updated
May 1, 2015
Sponsor
International Vaccine Institute
Collaborators
Indian Council of Medical Research, National Institute of Cholera and Enteric Diseases, India, Shantha Biotechnics Limited, Institute of Child Health
1. Study Identification
Unique Protocol Identification Number
NCT00548054
Brief Title
Safety and Immunogenicity of a Killed Oral Cholera Vaccine in Infants
Official Title
Safety and Immunogenicity of a Killed Oral Cholera Vaccine Among Infants 10 Weeks to Less Than 12 Months of Age When Given Concomitantly With EPI Vaccines
Study Type
Interventional
2. Study Status
Record Verification Date
May 2015
Overall Recruitment Status
Unknown status
Study Start Date
December 2015 (undefined)
Primary Completion Date
August 2016 (Anticipated)
Study Completion Date
December 2016 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
International Vaccine Institute
Collaborators
Indian Council of Medical Research, National Institute of Cholera and Enteric Diseases, India, Shantha Biotechnics Limited, Institute of Child Health
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cholera, Diarrhea, Vibrio Infections
Keywords
cholera, vaccine, Kolkata, West Bengal, India, immunogenicity, safety, infants, expanded programme on immunization
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
300 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Vaccine Group for Vibriocidal Assay
Arm Type
Experimental
Arm Description
Killed whole cell cholera vaccine bled at day 42 for vibriocidal assay
Arm Title
Vaccine Group for EPI Assay
Arm Type
Experimental
Arm Description
Killed whole cell cholera vaccine bled at day 56 for EPI immunogenicity testing
Arm Title
Placebo Group for Vibriocidal Assay
Arm Type
Placebo Comparator
Arm Description
Placebo bled at day 42 for vibriocidal assay
Arm Title
Placebo Group for EPI Assay
Arm Type
Placebo Comparator
Arm Description
Placebo bled at day 56 for EPI immunogenicity testing
Arm Title
Vaccine Group for Vibriocidal and Measles Assay
Arm Type
Experimental
Arm Description
Killed whole cell cholera vaccine bled at day 14 and 28 for measles immunogenicity testing
Arm Title
Placebo Group for Vibriocidal and Measles Assay
Arm Type
Placebo Comparator
Arm Description
Placebo bled at day 14 and 28 for measles immunogenicity testing
Intervention Type
Biological
Intervention Name(s)
Bivalent killed oral cholera vaccine
Other Intervention Name(s)
Shanchol
Intervention Description
Oral, 1.5 ml, given 2 times at least 14 days apart
Intervention Type
Biological
Intervention Name(s)
Killed Escherichia coli K12 placebo
Intervention Description
oral, 1.5 ml per dose
Primary Outcome Measure Information:
Title
Safety: proportion of subjects with diarrhea
Time Frame
entire study period
Title
Immunogenicity: proportion of subjects exhibiting 4-fold or greater rises in titers of serum vibriocidal antibodies, relative to baseline
Time Frame
14 days after each dose
Secondary Outcome Measure Information:
Title
Geometric mean serum vibriocidal titers
Time Frame
14 days after each dose
Title
Proportion of subjects with any of the following: a) immediate reactions 30 minutes and up to 3 days after each dose, b) serious adverse events occurring during the trial, c) any adverse event
Time Frame
entire study period
Title
Proportion of subjects with ≥ 0.1 mIU/ml of anti-diphtheria toxoid antibodies
Time Frame
28 days after the third DPT dose
Title
Proportion of subjects with ≥ 0.1 mIU/ml of anti-tetanus toxoid antibodies
Time Frame
28 days after the third DPT dose
Title
For initially seronegative subjects: proportion of subjects with ≥ 15 EU/ml of anti-pertussis IgG and for initially seropositive subjects, proportion with antibody titers equal to or greater than the initial titers prior to vaccination
Time Frame
28 days after DPT dose
Title
Proportion of subjects with ≥ 10 mIU/ml of anti-HbS antibody
Time Frame
28 days after the third dose of Hepatitis B vaccine
Title
Proportion of subjects with ≥ 8 fold dilution of anti-polio virus 1, 2, or 3 antibodies by micro-neutralization test
Time Frame
28 days after the fourth dose of OPV
Title
Proportion of subjects with >150 mIU/ml measles IgG antibodies
Time Frame
28 days after single dose of measles vaccine
10. Eligibility
Sex
All
Minimum Age & Unit of Time
10 Weeks
Maximum Age & Unit of Time
11 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria, Infants 10 weeks to 6 months of age at Day 0:
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:
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)
Written informed consent obtained from their parents/guardians
Healthy subjects as determined by:
Medical history
Physical examination
Clinical judgment of the investigator
Inclusion Criteria, Infants 9 months to less than 12 months
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:
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)
Written informed consent obtained from their parents/guardians
Healthy subjects as determined by:
Medical history
Physical examination
Clinical judgment of the investigator
Exclusion Criteria, Infants 10 weeks to 6 months of age at Day 0:
Ongoing serious chronic disease
Immunocompromising condition or therapy
Diarrhea (having more frequent watery stools than usual within a 24 hour period) 6 weeks prior to enrollment
Intake of any anti-diarrheal medicine in the past week
Irritability, loss of appetite, general ill-feeling or vomiting in the past 24 hours
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
Receipt of antibiotics in past 14 days
Receipt of killed oral cholera vaccine
Receipt of live or killed enteric vaccine in 2 months
Receipt of DTwP1, OPV1 or Hepatitis B2 vaccines
One or two episodes of diarrhea lasting for more than 2 weeks in the past 2 months
One or two episodes of abdominal pain lasting for more than 2 weeks in the past 2 months
Z-score of < -2 on the weight for age WHO Child Growth Standards
Exclusion Criteria, Infants 9 months to less than 12 months:
Ongoing serious chronic disease
Immunocompromising condition or therapy
Diarrhea (3 or more loose/watery stools within a 24 hour period) 6 weeks prior to enrollment
Intake of any anti-diarrheal medicine in the past week
Abdominal pain/cramps, loss of appetite, general ill-feeling or vomiting in the past 24 hours
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
Receipt of antibiotics in past 14 days
Receipt of killed oral cholera vaccine
Receipt of live or killed enteric vaccine in last 4 weeks
Receipt of measles-containing vaccine (MCV)
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
Disease episode potentially related to measles
receipt of blood, blood products or a parenteral immunoglobulin preparation in past 3 months
History of anaphylaxis, any serious vaccine reaction, allergy to eggs, egg products or to any measles vaccine component
Any condition which in the opinion of the investigator might interfere with the evaluation of the study objectives
Z-score of < -2 on the weight for age WHO Child Growth Standards
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vijayalaxmi Mogasale, MD
Phone
82-2-881-1151
Email
vlmogasale@ivi.int
First Name & Middle Initial & Last Name or Official Title & Degree
Binod Sah, MBBS, MS
Phone
82-2-881-1149
Email
bsah@ivi.int
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alok K Deb, PhD, MDDS
Organizational Affiliation
National Institute of Cholera and Enteric Disease
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institute of Cholera and Enteric Disease
City
Kolkata
State/Province
West Bengal
Country
India
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alok K Deb, PhD, MBBS
Phone
91-33-2363-3373
Email
adeb2@yahoo.com
First Name & Middle Initial & Last Name & Degree
Alok K Deb, PhD, MBBS
12. IPD Sharing Statement
Learn more about this trial
Safety and Immunogenicity of a Killed Oral Cholera Vaccine in Infants
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