CholeraPhase 4NCT05453253
Immune Response to a Delayed Second Dose of Oral Cholera Vaccine
A Phase 4 study testing Delayed second dose of oral cholera vaccine, Euvichol-Plus and Oral cholera vaccine, Euvichol-Plus, according to manufacturer notice in people with Cholera and Vibrio Cholerae Infection, run by Epicentre at 1 site in Guinea.
Trial summary
Immune response to a delayed second dose of oral cholera vaccine A randomized, controlled, non-inferiority immunogenicity trial in Conakry, The Republic of Guinea Read more about this study
- Who is it for?
- Ages 1 year to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Cholera, Vibrio Cholerae Infection
- What is being tested?
- Delayed second dose of oral cholera vaccine, Euvichol-Plus and Oral cholera vaccine, Euvichol-Plus, according to manufacturer notice
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 456 participants
- Where
- 1 siteGuinea
- Study dates
- 20 Jul 2022to 1 Jul 2024
- Phase
- Phase 4
- 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 to 40 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Any healthy individual ≥ 1 year-old and younger than 40 years old , eligible for OCV vaccination (not suffering from a medical condition that contraindicates vaccination, i.e. any acute illness, including acute gastrointestinal illness or acute febrile illness).
- Living in the study area with no plan to move away over the study period (up to 18 months).
- Who provided written informed consent or whose representative (mother, father or main caretaker) provided written informed consent in case of individuals younger than 18 years. A written assent will also be obtained from adolescents (10-17 years)
- An individual who (or whose mother, father or main caretaker) is, based on the judgment of the investigator, capable of complying with the study requirements.
Who cannot join
- Known history of hypersensitivity reactions to other vaccines.
- Individual acutely ill or with signs of infection at the time of enrolment (e.g. fever > 38⁰C)
- Gastrointestinal symptoms including nausea, vomiting, diarrhea, or decreased appetite within 24 hours prior to study initiation .
- Diarrhea, administration of antidiarrheal drugs or antibiotics to treat diarrhea or abdominal pain either lasting 2 weeks or longer within 6 months prior to study initiation, or occurring during the week before study initiation.
- Other vaccination within 1 week prior to study initiation or planned vaccination during the following month after vaccine intake .
- Participation in another trial with investigational product within 1 month prior to study initiation.
Show all 12Show fewer
- Pregnant (as determined by a urine test on the day of each vaccination) or lactating women, women of reproductive age planning pregnancy before the end of the study period (up to minimum 18 months).
- An individual thought to have difficulty participating in the study due to other reasons (such as mental disorders, alcohol or drug intoxication), based on the judgment of the investigator.
- History of cholera vaccination or history of cholera as diagnosed by a medical person in a health facility (with or without laboratory confirmation).
- Severe chronic diseases or medical conditions, based on the medical judgment of the investigator, such as known low hemoglobin level or symptomatic anemia, severe acute malnutrition, chronic infection (e.g. tuberculosis), sequel of poliomyelitis, immunodeficiency due to symptomatic HIV/AIDS.
- Based on participant verbal reporting of the participant at inclusion, more than two persons in households <5 persons or three participants in households ≥ 5 persons.
- Thrombocytopenia or bleeding disorders or other known contraindication to venipuncture. Severe medical condition that contraindicates vaccination. In particular, a) known history of immune function disorders; or b) current use of steroids cytotoxic drugs, immunosuppressant, immune modifying drug, Prednisolone, Azathioprine, Cyclosporin, Interferon, G-CSF, Tacrolimus, Everolimus, Sirolimus; or c) known active malignancy with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years; or d) known uncompensated NYHA Class 3 or 4 congestive heart failure; or e) known myocardial infarction within the previous 6 months; or f) known neurological and/or psychiatric disorder.
Trial locations and contacts
1 site in 1 country.
About this study
Immune response to a delayed second dose of oral cholera vaccine
A randomized, controlled, non-inferiority immunogenicity trial in Conakry, The Republic of Guinea
Read the detailed description
Manufacturers of oral cholera vaccine (OCV) recommend a 7- or 14-days interval between two doses. To carry out two rounds of mass vaccination within this delay is not always feasible and many campaigns implemented to date have used a longer interval. Recent evidence indicates that an extended interval between OCV doses might result in equivalent seroconversion rates and in an improved boosting of mucosal immune responses following the second dose. To guide future OCV vaccination campaigns and improve cholera prevention, it is important to demonstrate the non-inferior immune response of an extended interval between OCV doses.
The Investigators aim to demonstrate the non-inferiority of the humoral immune response between individuals receiving a second Euvichol-Plus® pre-qualified OCV dose either 6 or 12 months after the initial dose and individuals receiving a second pre-qualified OCV dose 14 days after the initial dose. The humoral immune response will be assessed as the post-vaccination titer of serum vibriocidal antibodies at 14 days post-2nd dose vaccination. Secondary outcomes include the comparison of the overall rate of vibriocidal seroconversion 14 days after either the first or the second vaccine dose. A subsample of individuals ≥ 18 years will have additional serological evaluation to characterize the kinetics of their antibody responses up to 6 months after the second OCV vaccine dose. Although the vaccine has an established and safe profile, occurrence of adverse events and serious adverse events following vaccination will be assessed (safety evaluation).
The study will be an open-label, randomized, controlled, non-inferiority immunogenicity trial comparing the humoral immune responses to OCV in two interventions arms (6 and 12 months interval between OCV doses) compared with a control arm (standard 14-day interval). In each arm, the aim is to recruit 152 individuals aged 1 to 40 year-old eligible for OCV vaccination from the general population (ie. 456 individuals in total). The sub-sample allowing characterizing the kinetics of the humoral response up to 6 months after the administration of the second dose will include 38 participants in each intervention and control arm, among the participants aged ≥ 18 years. In total, 456 individuals will be recruited.
The study will be conducted in Conakry, in the Republic of Guinea. Participants will be primarily enrolled in the commune of Dixinn on a voluntary basis. All participants in the intervention and control arms will be invited to a first visit for assessment of eligibility and 1st OCV dose, followed by a visit 14 days after the 1st OCV dose for blood sampling. According to the study arm, the 2nd OCV dose will be administered at 14 days, 6 months or 1 year after the 1st dose and will be followed by a visit 14 days later for blood sampling. Participants in the sub-study will be invited to additional study visits (up to twelve visits in total) for blood sampling. At each visit, blood will be drawn for immunologic analyses.
- Conditions
- Cholera, Vibrio Cholerae Infection
- Being tested
- Delayed second dose of oral cholera vaccine, Euvichol-Plus, Oral cholera vaccine, Euvichol-Plus, according to manufacturer notice
- Keywords
- Delayed vaccine, Cholera, non-inferiority
- Medical subject headings
- Cholera
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Delayed second dose of oral cholera vaccine, Euvichol-PlusBiological
The intervention arms (6 and 12 months) will modify the recommended interval for administration of the second vaccine dose, which will be extended to 6 and 12 months according to the intervention arm.
Oral cholera vaccine, Euvichol-Plus, according to manufacturer noticeBiological
Euvichol-Plus, a WHO prequalified oral cholera vaccine, contains modified killed whole cell vaccine of formalin killed Vibrio cholerae strains of O1 Inaba, O1 Ogawa and O139.
In the control arm, participants will receive the Euvichol-Plus following the manufacturer recommendations: two doses administered orally 14 days apart for individuals aged ≥1 year.
| Study group | Role | What they receive |
|---|---|---|
| interventional 6 months interval between OCV doses | Experimental | This intervention arm will modify the recommended interval for administration of the second Euvichol-Plus®, which will be extended to 6 months. Receives: Biological: Delayed second dose of oral cholera vaccine, Euvichol-Plus |
| interventional 12 months interval between OCV doses | Experimental | This intervention arm will modify the recommended interval for administration of the second Euvichol-Plus®, which will be extended to 12 months. Receives: Biological: Delayed second dose of oral cholera vaccine, Euvichol-Plus |
| control arm (standard 14-day interval) | Active comparator | Participants will receive the oral cholera vaccine, Euvichol-Plus®, according to the manufacturer instructions: 2 doses two weeks apart. Receives: Biological: Oral cholera vaccine, Euvichol-Plus, according to manufacturer notice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum vibriocidal antibody specific to V. cholerae O1, Inaba, Ogawa and O139 strains
Serum vibriocidal antibody Geometric Mean Titre (GMT)
Measured: 14 days after the administration of the second vaccine dose
Secondary outcomes (6)
Serum vibriocidal antibody specific to V. cholerae O1, Inaba, Ogawa and O139 strains
Serum vibriocidal antibody Geometric Mean Titre (GMT)
Measured: Just before and 14 days after administration of the first dose and and just before the second OCV dose
Serum vibriocidal anti-OSP IgA, IgG, IgM
Serum vibriocidal anti-OSP IgA, IgG, IgM titres measured using Enzyme-linked immunosorbend essay (ELISA)
Measured: Just before and 14 days after administration of the first and the second OCV dose
Anti-CtxB immunoglobulines
Anti-CtxB immunoglobulines titres measured using Enzyme-linked immunosorbend essay (ELISA)
Measured: Just before and 14 days after administration of the first and the second OCV dose
Immediate Adverse Events (IAEs) (Safety)
All participants will be observed by clinicians for 30 minutes after each vaccination to monitor for any immediate adverse events (IAEs)
Measured: Up to 30 minutes after each OCV dose
Adverse events (AEs) (Safety)
Solicited and unsolicited AEs will be actively monitored by clinicians at the study visits for 14 days following administration of each vaccine dose.
Measured: Until 14 days after the administration of the first and the second OCV dose
Serious Adverse Events (SAEs) (Safety)
SAEs will be monitored by clinicians up to end of the participants' follow-up.
Measured: Up to end of the participants' follow-up i.e. 18months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2022
- Study start20 Jul 2022
- Primary completion1 Feb 2024 (estimated)
- Study completion1 Jul 2024 (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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Considering 20% loss of follow-up and sampling failures at 14 days post 2nd OCV, the aim is to enroll 152 participants per arm for the analysis. Thus 456 (3\*152) participants will be recruited. Also, participants with a blood sampling failure at baseline (pre-1st OCV) will be replaced and withdrawn before randomization. Thus 456 (3\*152) participants with an appropriate blood sample at baseline will be randomisedecruited.
- Masking
- None (open label)
- Enrolment
- 456 participants (actual)
Sponsor and investigators
- Lead sponsor
- Epicentre
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, Guinea, Massachusetts General Hospital, Médecins Sans Frontières, Belgium
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05453253
- Sponsor's protocol ID
- OCV_DelayedProtocol
- Status last verified
- Mar 2023
- First submitted
- 1 Jun 2022
- Last updated
- 7 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Response to a Delayed Second Dose of Oral Cholera Vaccine
- ClinicalTrials.gov ID
- NCT05453253
- Acronym / sponsor ID
- OCV_DelayedProtocol
- Conditions
- Cholera, Vibrio Cholerae Infection
- Keywords
- Delayed vaccine, Cholera, non-inferiority
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 456 participants (actual)
- Lead sponsor
- EpicentreUniversity, hospital or other
- Collaborators
- Ministry of Health, Guinea, Massachusetts General Hospital, Médecins Sans Frontières, Belgium
- Study start
- 20 Jul 2022 (actual)
- Primary completion
- 1 Feb 2024 (estimated)
- Study completion
- 1 Jul 2024 (estimated)
- First posted
- 12 Jul 2022 (actual)
- 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.
Immune response to a delayed second dose of oral cholera vaccine
A randomized, controlled, non-inferiority immunogenicity trial in Conakry, The Republic of Guinea
Detailed description
Manufacturers of oral cholera vaccine (OCV) recommend a 7- or 14-days interval between two doses. To carry out two rounds of mass vaccination within this delay is not always feasible and many campaigns implemented to date have used a longer interval. Recent evidence indicates that an extended interval between OCV doses might result in equivalent seroconversion rates and in an improved boosting of mucosal immune responses following the second dose. To guide future OCV vaccination campaigns and improve cholera prevention, it is important to demonstrate the non-inferior immune response of an extended interval between OCV doses.
The Investigators aim to demonstrate the non-inferiority of the humoral immune response between individuals receiving a second Euvichol-Plus® pre-qualified OCV dose either 6 or 12 months after the initial dose and individuals receiving a second pre-qualified OCV dose 14 days after the initial dose. The humoral immune response will be assessed as the post-vaccination titer of serum vibriocidal antibodies at 14 days post-2nd dose vaccination. Secondary outcomes include the comparison of the overall rate of vibriocidal seroconversion 14 days after either the first or the second vaccine dose. A subsample of individuals ≥ 18 years will have additional serological evaluation to characterize the kinetics of their antibody responses up to 6 months after the second OCV vaccine dose. Although the vaccine has an established and safe profile, occurrence of adverse events and serious adverse events following vaccination will be assessed (safety evaluation).
The study will be an open-label, randomized, controlled, non-inferiority immunogenicity trial comparing the humoral immune responses to OCV in two interventions arms (6 and 12 months interval between OCV doses) compared with a control arm (standard 14-day interval). In each arm, the aim is to recruit 152 individuals aged 1 to 40 year-old eligible for OCV vaccination from the general population (ie. 456 individuals in total). The sub-sample allowing characterizing the kinetics of the humoral response up to 6 months after the administration of the second dose will include 38 participants in each intervention and control arm, among the participants aged ≥ 18 years. In total, 456 individuals will be recruited.
The study will be conducted in Conakry, in the Republic of Guinea. Participants will be primarily enrolled in the commune of Dixinn on a voluntary basis. All participants in the intervention and control arms will be invited to a first visit for assessment of eligibility and 1st OCV dose, followed by a visit 14 days after the 1st OCV dose for blood sampling. According to the study arm, the 2nd OCV dose will be administered at 14 days, 6 months or 1 year after the 1st dose and will be followed by a visit 14 days later for blood sampling. Participants in the sub-study will be invited to additional study visits (up to twelve visits in total) for blood sampling. At each visit, blood will be drawn for immunologic analyses.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Considering 20% loss of follow-up and sampling failures at 14 days post 2nd OCV, the aim is to enroll 152 participants per arm for the analysis. Thus 456 (3*152) participants will be recruited. Also, participants with a blood sampling failure at baseline (pre-1st OCV) will be replaced and withdrawn before randomization. Thus 456 (3*152) participants with an appropriate blood sample at baseline will be randomisedecruited.
| Arm | Type | Receives |
|---|---|---|
| interventional 6 months interval between OCV doses | Experimental | Biological: Delayed second dose of oral cholera vaccine, Euvichol-PlusThis intervention arm will modify the recommended interval for administration of the second Euvichol-Plus®, which will be extended to 6 months. |
| interventional 12 months interval between OCV doses | Experimental | Biological: Delayed second dose of oral cholera vaccine, Euvichol-PlusThis intervention arm will modify the recommended interval for administration of the second Euvichol-Plus®, which will be extended to 12 months. |
| control arm (standard 14-day interval) | Active comparator | Biological: Oral cholera vaccine, Euvichol-Plus, according to manufacturer noticeParticipants will receive the oral cholera vaccine, Euvichol-Plus®, according to the manufacturer instructions: 2 doses two weeks apart. |
Who may qualify
- Ages
- 1 year to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Any healthy individual ≥ 1 year-old and younger than 40 years old , eligible for OCV vaccination (not suffering from a medical condition that contraindicates vaccination, i.e. any acute illness, including acute gastrointestinal illness or acute febrile illness).
- Living in the study area with no plan to move away over the study period (up to 18 months).
- Who provided written informed consent or whose representative (mother, father or main caretaker) provided written informed consent in case of individuals younger than 18 years. A written assent will also be obtained from adolescents (10-17 years)
- An individual who (or whose mother, father or main caretaker) is, based on the judgment of the investigator, capable of complying with the study requirements.
Key exclusion criteria (12 listed)
- Known history of hypersensitivity reactions to other vaccines.
- Individual acutely ill or with signs of infection at the time of enrolment (e.g. fever > 38⁰C)
- Gastrointestinal symptoms including nausea, vomiting, diarrhea, or decreased appetite within 24 hours prior to study initiation .
- Diarrhea, administration of antidiarrheal drugs or antibiotics to treat diarrhea or abdominal pain either lasting 2 weeks or longer within 6 months prior to study initiation, or occurring during the week before study initiation.
- Other vaccination within 1 week prior to study initiation or planned vaccination during the following month after vaccine intake .
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 |
|---|---|---|
| Delayed second dose of oral cholera vaccine, Euvichol-PlusThe intervention arms (6 and 12 months) will modify the recommended interval for administration of the second vaccine dose, which will be extended to 6 and 12 months according to the intervention arm. | Biological | interventional 12 months interval between OCV doses, interventional 6 months interval between OCV doses |
| Oral cholera vaccine, Euvichol-Plus, according to manufacturer noticeEuvichol-Plus, a WHO prequalified oral cholera vaccine, contains modified killed whole cell vaccine of formalin killed Vibrio cholerae strains of O1 Inaba, O1 Ogawa and O139. In the control arm, participants will receive the Euvichol-Plus following the manufacturer recommendations: two doses administered orally 14 days apart for individuals aged ≥1 year. | Biological | control arm (standard 14-day interval) |
Primary outcome
Serum vibriocidal antibody specific to V. cholerae O1, Inaba, Ogawa and O139 strains
Time frame: 14 days after the administration of the second vaccine dose
Serum vibriocidal antibody Geometric Mean Titre (GMT)
6 secondary outcomes
Serum vibriocidal antibody specific to V. cholerae O1, Inaba, Ogawa and O139 strains
Time frame: Just before and 14 days after administration of the first dose and and just before the second OCV dose
Serum vibriocidal anti-OSP IgA, IgG, IgM
Time frame: Just before and 14 days after administration of the first and the second OCV dose
Anti-CtxB immunoglobulines
Time frame: Just before and 14 days after administration of the first and the second OCV dose
Immediate Adverse Events (IAEs) (Safety)
Time frame: Up to 30 minutes after each OCV dose
Adverse events (AEs) (Safety)
Time frame: Until 14 days after the administration of the first and the second OCV dose
Serious Adverse Events (SAEs) (Safety)
Time frame: Up to end of the participants' follow-up i.e. 18months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2023.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Delayed second dose of oral cholera vaccine, Euvichol-Plus and Oral cholera vaccine, Euvichol-Plus, according to manufacturer notice in people with Cholera and Vibrio Cholerae Infection, run by Epicentre at 1 site in Guinea.
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 4 inclusion and 12 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 7 Mar 2023. 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 Guinea. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
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?
Serum vibriocidal antibody specific to V. cholerae O1, Inaba, Ogawa and O139 strains (time frame: 14 days after the administration of the second vaccine dose). 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 7 Mar 2023.