CholeraPhase 2NCT01233362
Study of Alternative Vaccination Schedule of Oral Cholera Vaccine
A Phase 2 study testing Modified killed oral cholera vaccine at 14 day interval and Modified killed oral cholera vaccine at 28 day interval in people with Cholera and Diarrhoea, run by International Vaccine Institute at 1 site in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year and olderHealthy volunteers can take part
- Conditions the study is for
- Cholera, Diarrhoea, Vibrio Infection
- What is being tested?
- Modified killed oral cholera vaccine at 14 day interval and Modified killed oral cholera vaccine at 28 day interval
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 386 participants
- Where
- 1 siteIndia
- Study dates
- Dec 2010to Feb 2013
- 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 1 year and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
India1 site
National Institute of Cholera and Enteric Diseases
Kolkata, West Bengal, 700010
About this study
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.
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.
Read the 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.
- Conditions
- Cholera, Diarrhoea, Vibrio Infection
- Being tested
- Modified killed oral cholera vaccine at 14 day interval, Modified killed oral cholera vaccine at 28 day interval
- Keywords
- Cholera, Vaccine, Kolkata, West Bengal, India, Immunogenicity, Vaccination Schedules
- 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.
Modified killed oral cholera vaccine at 14 day intervalBiological
Also called Shancol
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.
Modified killed oral cholera vaccine at 28 day intervalBiological
Also called Shancol
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Adults; 14 days interval | Active comparator | 89 Adults (=> 18 years aged) receiving study agents (Vaccine/Placebo) at 14 days inter-dose interval Receives: Biological: Modified killed oral cholera vaccine at 14 day interval |
| Arm 2: Adults; 28 days interval | Active comparator | 89 Adults (=> 18 years aged) receiving study agents (Vaccine/Placebo) at 28 days inter-dose interval Receives: Biological: Modified killed oral cholera vaccine at 28 day interval |
| Arm 3: children; 14 days interval | Active comparator | 89 children (1-17 years aged) receiving study agents (Vaccine/Placebo) at 14 days inter-dose interval Receives: Biological: Modified killed oral cholera vaccine at 14 day interval |
| Arm 4: children; 28 days interval | Active comparator | 89 children (1-17 years aged) receiving study agents (Vaccine/Placebo) at 28 days inter-dose interval Receives: Biological: Modified killed oral cholera vaccine at 28 day interval |
| Arm 5: Adults; 14 days Interval | Active comparator | 15 Adults (=> 18 years aged) receiving study agents (Vaccine/Placebo) at 14 days inter-dose interval Receives: Biological: Modified killed oral cholera vaccine at 14 day interval |
| Arm 6: Adults; 28 days interval | Active comparator | 15 Adults (=> 18 years aged) receiving study agents (Vaccine/Placebo) at 28 days inter-dose interval Receives: Biological: Modified killed oral cholera vaccine at 28 day interval |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 14 days after the last dose of the study agent
Secondary outcomes (4)
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
Measured: 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.
Measured: 14 days after each dose of study agent
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
- 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
Measured: upto 1.5 months after the first dose of study agent
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
Measured: upto 1.5 months after the first dose of study agent
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2010 (estimated)
- Study startDec 2010
- Primary completionFeb 2013
- Study completionFeb 2013
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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 386 participants (actual)
Sponsor and investigators
- Lead sponsor
- International Vaccine Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Cholera and Enteric Diseases, India, Indian Council of Medical Research, Shantha Biotechnics Limited
- Responsible party
- Sponsor
- Investigators
- Dipika Sur, MD, DPH, Principal investigator, National Institute of Cholera and Enteric Diseases, Kolkata, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01233362
- Sponsor's protocol ID
- CR-WC-05
- Status last verified
- Aug 2012
- First submitted
- 11 Oct 2010
- Last updated
- 25 Sep 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01233362
- Acronym / sponsor ID
- CR-WC-05
- Conditions
- Cholera, Diarrhoea, Vibrio Infection
- Keywords
- Cholera, Vaccine, Kolkata, West Bengal, India, Immunogenicity, Vaccination Schedules
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 386 participants (actual)
- Lead sponsor
- International Vaccine InstituteUniversity, hospital or other
- Collaborators
- National Institute of Cholera and Enteric Diseases, India, Indian Council of Medical Research, Shantha Biotechnics Limited
- Study start
- Dec 2010
- Primary completion
- Feb 2013 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 3 Nov 2010 (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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Adults; 14 days interval | Active comparator | Biological: Modified killed oral cholera vaccine at 14 day interval89 Adults (=> 18 years aged) receiving study agents (Vaccine/Placebo) at 14 days inter-dose interval |
| Arm 2: Adults; 28 days interval | Active comparator | Biological: Modified killed oral cholera vaccine at 28 day interval89 Adults (=> 18 years aged) receiving study agents (Vaccine/Placebo) at 28 days inter-dose interval |
| Arm 3: children; 14 days interval | Active comparator | Biological: Modified killed oral cholera vaccine at 14 day interval89 children (1-17 years aged) receiving study agents (Vaccine/Placebo) at 14 days inter-dose interval |
| Arm 4: children; 28 days interval | Active comparator | Biological: Modified killed oral cholera vaccine at 28 day interval89 children (1-17 years aged) receiving study agents (Vaccine/Placebo) at 28 days inter-dose interval |
| Arm 5: Adults; 14 days Interval | Active comparator | Biological: Modified killed oral cholera vaccine at 14 day interval15 Adults (=> 18 years aged) receiving study agents (Vaccine/Placebo) at 14 days inter-dose interval |
| Arm 6: Adults; 28 days interval | Active comparator | Biological: Modified killed oral cholera vaccine at 28 day interval15 Adults (=> 18 years aged) receiving study agents (Vaccine/Placebo) at 28 days inter-dose interval |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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:
Key exclusion criteria (13 listed)
- 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
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 |
|---|---|---|
| Modified killed oral cholera vaccine at 14 day intervalAlso: ShancolThe 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. | Biological | Arm 1: Adults; 14 days interval, Arm 3: children; 14 days interval, Arm 5: Adults; 14 days Interval |
| Modified killed oral cholera vaccine at 28 day intervalAlso: ShancolThe 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. | Biological | Arm 2: Adults; 28 days interval, Arm 4: children; 28 days interval, Arm 6: Adults; 28 days interval |
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
Time frame: 14 days after the last dose of the study agent
4 secondary outcomes
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
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
Proportion of subjects given 2 doses of study agent given 14 and 28 days apart with adverse events.
Time frame: upto 1.5 months after the first dose of study agent
Proportion of subjects given 2 doses of vaccine given 14 and 28 days apart with significant immunological responses to the alternate assays under exploration
Time frame: upto 1.5 months after the first dose of study agent
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2013.
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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.
Dipika Sur, MD, DPH principal investigator
National Institute of Cholera and Enteric Diseases, Kolkata, India
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 Modified killed oral cholera vaccine at 14 day interval and Modified killed oral cholera vaccine at 28 day interval in people with Cholera and Diarrhoea, 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 6 inclusion and 13 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: finished, as of the sponsor's last update on 25 Sep 2013. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). 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 25 Sep 2013.