CholeraPhase 2NCT00548054
Safety and Immunogenicity of a Killed Oral Cholera Vaccine in Infants
A Phase 2 study testing Bivalent killed oral cholera vaccine in people with Cholera and Diarrhea, run by International Vaccine Institute at 1 site in India.
Trial 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… Read more about this study
- Who is it for?
- Ages 10 weeks to 11 monthsHealthy volunteers can take part
- Conditions the study is for
- Cholera, Diarrhea, Vibrio Infections
- What is being tested?
- Bivalent killed oral cholera vaccine
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 300 participants
- Where
- 1 siteIndia
- Study dates
- Dec 2015to Dec 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 weeks to 11 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
Show all 40Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
India1 site
National Institute of Cholera and Enteric Disease
Kolkata, West Bengal
Alok K Deb, PhD, MBBS, 91-33-2363-3373, adeb2@yahoo.com
Alok K Deb, PhD, MBBS
About this study
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
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).
Read the 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.
- Conditions
- Cholera, Diarrhea, Vibrio Infections
- Being tested
- Bivalent killed oral cholera vaccine, Killed Escherichia coli K12 placebo
- Keywords
- cholera, vaccine, Kolkata, West Bengal, India, immunogenicity, safety, infants, expanded programme on immunization
- Medical subject headings
- Cholera, Diarrhea, Vibrio Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bivalent killed oral cholera vaccineBiological
Also called Shanchol
Oral, 1.5 ml, given 2 times at least 14 days apart
Killed Escherichia coli K12 placeboBiological
oral, 1.5 ml per dose
| Study group | Role | What they receive |
|---|---|---|
| Vaccine Group for Vibriocidal Assay | Experimental | Killed whole cell cholera vaccine bled at day 42 for vibriocidal assay Receives: Biological: Bivalent killed oral cholera vaccine |
| Vaccine Group for EPI Assay | Experimental | Killed whole cell cholera vaccine bled at day 56 for EPI immunogenicity testing Receives: Biological: Bivalent killed oral cholera vaccine |
| Placebo Group for Vibriocidal Assay | Placebo comparator | Placebo bled at day 42 for vibriocidal assay Receives: Biological: Killed Escherichia coli K12 placebo |
| Placebo Group for EPI Assay | Placebo comparator | Placebo bled at day 56 for EPI immunogenicity testing Receives: Biological: Killed Escherichia coli K12 placebo |
| Vaccine Group for Vibriocidal and Measles Assay | Experimental | Killed whole cell cholera vaccine bled at day 14 and 28 for measles immunogenicity testing Receives: Biological: Bivalent killed oral cholera vaccine |
| Placebo Group for Vibriocidal and Measles Assay | Placebo comparator | Placebo bled at day 14 and 28 for measles immunogenicity testing Receives: Biological: Killed Escherichia coli K12 placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: proportion of subjects with diarrhea
Measured: entire study period
Immunogenicity: proportion of subjects exhibiting 4-fold or greater rises in titers of serum vibriocidal antibodies, relative to baseline
Measured: 14 days after each dose
Secondary outcomes (8)
Geometric mean serum vibriocidal titers
Measured: 14 days after each dose
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
Measured: entire study period
Proportion of subjects with ≥ 0.1 mIU/ml of anti-diphtheria toxoid antibodies
Measured: 28 days after the third DPT dose
Proportion of subjects with ≥ 0.1 mIU/ml of anti-tetanus toxoid antibodies
Measured: 28 days after the third DPT dose
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
Measured: 28 days after DPT dose
Proportion of subjects with ≥ 10 mIU/ml of anti-HbS antibody
Measured: 28 days after the third dose of Hepatitis B vaccine
Proportion of subjects with ≥ 8 fold dilution of anti-polio virus 1, 2, or 3 antibodies by micro-neutralization test
Measured: 28 days after the fourth dose of OPV
Proportion of subjects with >150 mIU/ml measles IgG antibodies
Measured: 28 days after single dose of measles vaccine
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2007 (estimated)
- Study startDec 2015
- Primary completionAug 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CholeraStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- International Vaccine Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Indian Council of Medical Research, National Institute of Cholera and Enteric Diseases, India, Shantha Biotechnics Limited, Institute of Child Health
- Responsible party
- Sponsor
- Investigators
- Alok K Deb, PhD, MDDS, Principal investigator, National Institute of Cholera and Enteric Disease
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00548054
- Sponsor's protocol ID
- CH-WC-01
- Status last verified
- May 2015
- First submitted
- 21 Oct 2007
- Last updated
- 4 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00548054
- Acronym / sponsor ID
- CH-WC-01
- Conditions
- Cholera, Diarrhea, Vibrio Infections
- Keywords
- cholera, vaccine, Kolkata, West Bengal, India, immunogenicity, safety, infants
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- International Vaccine InstituteUniversity, hospital or other
- Collaborators
- Indian Council of Medical Research, National Institute of Cholera and Enteric Diseases, India, Shantha Biotechnics Limited, Institute of Child Health
- Study start
- Dec 2015
- Primary completion
- Aug 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 23 Oct 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Vaccine Group for Vibriocidal Assay | Experimental | Biological: Bivalent killed oral cholera vaccineKilled whole cell cholera vaccine bled at day 42 for vibriocidal assay |
| Vaccine Group for EPI Assay | Experimental | Biological: Bivalent killed oral cholera vaccineKilled whole cell cholera vaccine bled at day 56 for EPI immunogenicity testing |
| Placebo Group for Vibriocidal Assay | Placebo comparator | Biological: Killed Escherichia coli K12 placeboPlacebo bled at day 42 for vibriocidal assay |
| Placebo Group for EPI Assay | Placebo comparator | Biological: Killed Escherichia coli K12 placeboPlacebo bled at day 56 for EPI immunogenicity testing |
| Vaccine Group for Vibriocidal and Measles Assay | Experimental | Biological: Bivalent killed oral cholera vaccineKilled whole cell cholera vaccine bled at day 14 and 28 for measles immunogenicity testing |
| Placebo Group for Vibriocidal and Measles Assay | Placebo comparator | Biological: Killed Escherichia coli K12 placeboPlacebo bled at day 14 and 28 for measles immunogenicity testing |
Who may qualify
- Ages
- 10 weeks to 11 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (40 listed)
- 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:
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bivalent killed oral cholera vaccineAlso: ShancholOral, 1.5 ml, given 2 times at least 14 days apart | Biological | Vaccine Group for EPI Assay, Vaccine Group for Vibriocidal Assay, Vaccine Group for Vibriocidal and Measles Assay |
| Killed Escherichia coli K12 placebooral, 1.5 ml per dose | Biological | Placebo Group for EPI Assay, Placebo Group for Vibriocidal Assay, Placebo Group for Vibriocidal and Measles Assay |
Primary outcome
Safety: proportion of subjects with diarrhea
Time frame: entire study period
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
8 secondary outcomes
Geometric mean serum vibriocidal titers
Time frame: 14 days after each dose
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
Proportion of subjects with ≥ 0.1 mIU/ml of anti-diphtheria toxoid antibodies
Time frame: 28 days after the third DPT dose
Proportion of subjects with ≥ 0.1 mIU/ml of anti-tetanus toxoid antibodies
Time frame: 28 days after the third DPT dose
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
Proportion of subjects with ≥ 10 mIU/ml of anti-HbS antibody
Time frame: 28 days after the third dose of Hepatitis B vaccine
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
Proportion of subjects with >150 mIU/ml measles IgG antibodies
Time frame: 28 days after single dose of measles vaccine
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alok K Deb, PhD, MDDS principal investigator
National Institute of Cholera and Enteric Disease
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bivalent killed oral cholera vaccine in people with Cholera and Diarrhea, run by International Vaccine Institute at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 40 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Vijayalaxmi Mogasale, MD (82-2-881-1151, vlmogasale@ivi.int), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety: proportion of subjects with diarrhea (time frame: entire study period). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2015.