Cholera Vaccination
Conditions
Keywords
Cholera Conjugate Vaccine, O Specific Polysaccharide, Recombinant Tetanus Toxoid Heavy Chain Fragment, Cholera Vaccine
Brief summary
This phase II study is intended to determine the immunogenicity and safety of single dose and two doses of OSP:rTTHc cholera conjugate vaccine (CCV) with or without alum adjuvant. The study will guide the future dosing schedule and formulation of CCV (with or without Aluminum phosphate adjuvant) expected to be needed in adults and children in cholera-endemic region.
Detailed description
This is phase II, randomized, controlled, safety and immunogenicity study of one and two doses of the of CCV 25 μg (with and without alum) in cholera-endemic region. A total of 390 eligible participants will be recruited in the study into 3 age cohorts. This will be a randomized, placebo-controlled, observer blind study in adults aged 18 to 45 years (cohort A) and children aged 5 to 17 years (cohort B) followed by a randomized, active-controlled, partial open label study in children aged 1 to 4 years (cohort C). The DSMB must review the safety data of each cohort and approve study continuation before investigational product administration of the next younger cohort is initiated (age descending study scheme). In cohort A, 50 adult participants aged 18 to 45 years will be randomly divided into 5 arms to receive the assigned investigational product as follows: Arm A1 (n=10): one dose of CCV 25 μg with alum and one dose of placebo at 6 months interval Arm A2 (n=10): one dose of CCV 25 μg without alum and one dose of placebo at 6 months interval Arm A3 (n=10): two doses of CCV 25 μg with alum at 6 months interval Arm A4 (n=10): two doses of CCV 25 μg without alum at 6 months interval Arm A5 (n=10): two doses of placebo at 6 months interval In cohort B, 90 children aged 5 to 17 years will be randomly divided into 5 arms to receive the assigned investigational product as follows: Arm B1 (n=20): one dose of CCV 25 μg with alum and one dose of placebo at 6 months interval Arm B2 (n=20): one dose of CCV 25 μg without alum and one dose of placebo at 6 months interval Arm B3 (n=20): two doses of CCV 25 μg with alum at 6 months interval Arm B4 (n=20): two doses of CCV 25 μg without alum at 6 months interval Arm B5 (n=10): two doses of placebo at 6 months interval In cohort C, 250 children aged 1 to 4 years will be randomly divided into 10 arms to receive the assigned investigational product as follows: Arm C1 (n=30): one dose of CCV 25 μg with alum and one dose of placebo at 6 months interval Arm C2 (n=30): one dose of CCV 25 μg without alum and one dose of placebo at 6 months interval Arm C3 (n=30): two doses of CCV 25 μg with alum at 6 months interval Arm C4 (n=30): two doses of CCV 25 μg without alum at 6 months interval Arm C5 (n=20): two doses of placebo at 6 months interval Arm C6 (n=30): two doses of Euvichol®-Plus at 2 weeks interval Arm C7 (n=20): one dose of CCV 25 μg with alum and one dose of Euvichol®-Plus at 6 months interval Arm C8 (n=20): one dose of CCV 25 μg without alum and one dose of Euvichol®-Plus at 6 months interval Arm C9 (n=20): one dose of Euvichol®-Plus and one dose of CCV 25 μg with alum at 6 months interval Arm C10 (n=20): one dose of Euvichol®-Plus and one dose of CCV 25 μg without alum at 6 months interval Route of vaccination: CCV 25 μg (with or without alum) and placebo are administered by intramuscular (IM) injection. Euvichol®-Plus is administered orally.
Interventions
BIOLOGICALOSP:rTTHc CCV 25 ㎍ with Aluminum phosphate
OSP:rTTHc Cholera Conjugate with Aluminum phosphate Cohort Arms A1, A3, B1, B3, C1, C3, C10
BIOLOGICALOSP:rTTHc CCV 25 ㎍ without Aluminum phosphate
OSP:rTTHc Cholera Conjugate without Aluminum phosphate Cohort Arms A2, A4, B2, B4, C2, C4
BIOLOGICALEuvichol®-Plus
V. cholerae O1 and O139 bivalent inactivated oral cholera vaccine cohort Arm C6
OTHERPlacebo
Sterile 0.9% sodium chloride cohort Arms A5, B5, C5
BIOLOGICALCCV with Aluminum, Euvichol®-Plus
1. OSP:rTTHc CCV 25 # with Aluminum phosphate OSP:rTTHc Cholera Conjugate with Aluminum phosphate 2. Euvichol®-Plus V. cholerae O1 and O139 bivalent inactivated oral cholera vaccine Cohort Arms C7, C9
BIOLOGICALCCV without Aluminum, Euvichol®-Plus
1. OSP:rTTHc CCV 25 # without Aluminum phosphate OSP:rTTHc Cholera Conjugate without Aluminum phosphate 2. Euvichol®-Plus V. cholerae O1 and O139 bivalent inactivated oral cholera vaccine Cohort Arms C8, C10
Sponsors
International Vaccine Institute
EuBiologics Co.,Ltd
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The study in cohort A and B will be conducted in an observer blinded manner. Observer-blind means only the designated study site personnel responsible for investigational product preparation will be aware of the investigational product allocation while all other individuals involved in the study (study participants, study investigators, study nurses, and all personnel assessing clinical outcomes) will be blinded to investigational product allocation until final database lock. The study in cohort C will be conducted mostly in an observer blinded manner i.e., the blind will be maintained between arms C1 to C5, between C7 and C8, and between C9 and C10, but will be partially open label (where blinding is not feasible due to the different routes of administration of assigned IP) between the different type of arms i.e. those receiving CCV (C1-5) vs comparator (C6) vs heterologous arms (C7-8 vs C9-10).
Intervention model description
This is phase II, randomized, controlled, safety and immunogenicity study of one and two doses of the of CCV 25 μg (with and without alum) in cholera-endemic region. A total of 390 eligible participants will be recruited in the study into 3 age cohorts
Eligibility
Sex/Gender
ALL
Age
1 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Individuals aged 1 to 45 years at consent 2. Participants/ Participants' legally authorized representative (LAR) willing to provide written informed consent to participate in the study voluntarily 3. Participants who can comply with the study requirements 4. Individuals in good health as determined by the outcome of medical history, physical examination, and the clinical judgment of the investigator
Exclusion criteria
1. Known history or allergy to investigational vaccine components or other medications, or any other allergies 2. Individuals with major congenital abnormalities 3. Known history of immune function disorders including immunodeficiency diseases (known HIV infection¥ or other immune function disorders) 4. Use of systemic steroids within past 6 months (\>10 mg/day prednisone equivalent for periods exceeding 2 consecutive weeks), or receive chemotherapy, radiation therapy or other immunosuppressive drugs within the past 6 months. 5. Any abnormality or chronic disease which in the opinion of the investigator might be detrimental for the safety of the participant and interfere with the assessment of the study objectives 6. Individuals with behavioral or cognitive impairment or psychiatric disease or neural disorders that, in the opinion of the investigator, could interfere with the participant's ability to participate in the trial 7. Individuals with splenectomy 8. Individuals with known bleeding disorders 9. Receipt of blood, blood-derived products, or immunoglobulin products in the past 3 months 10. Individuals who have received other vaccines from 4 weeks prior to the first dose of test vaccination or planned to receive any vaccine within 4 weeks of the last dose of the investigational product. 11. Individuals with active or known previous Vibrio cholerae infection 12. Individuals with a history of severe diarrhea in the last 6 months requiring care at a medical facility lasting 24 hours or more 13. Individuals with prior receipt of a cholera vaccine in the last 5 years 14. Any female participant who is lactating or pregnant 15. Females of childbearing potential who do not agree to use an effective birth control method for at least 4 weeks before the screening and up to 12 weeks after the study vaccination. 16. Individuals enrolled in another clinical trial within 6 months prior to enrollment, concomitantly enrolled or scheduled to be enrolled in another trial during study period 17. Individuals who are research staff involved with the clinical trial or family/household members of research staff 18. As per Investigator's medical judgement, an individual could also be excluded from the study despite meeting all inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Seroconversion of Serum vibriocidal antibody titers responses to V. cholerae O1 Inaba and O1 Ogawa at 28 days after one dose vaccination of CCV 25 μg (with or without alum) in adults (aged 18 to 45 years) and in children (aged 1 to 17 years). | Baseline and at 28 days post the first dose of either CCV with alum, CCV without alum or placebo | \- Proportion of participants achieving seroconversion (defined as at least 4-fold increase from baseline) of serum vibriocidal antibody titers at 28 days after one dose vaccination of CCV (with or without alum) 25 μg / placebo |
| GMT of Serum vibriocidal antibody titers to V. cholerae O1 Inaba and O1 Ogawa after one dose of CCV 25 μg (with or without alum) in adults (aged 18 to 45 years) and in children (aged 1 to 17 years) | Baseline and at 28 days post the first dose of either CCV with alum, CCV without alum or placebo | \- GMT of serum vibriocidal antibody titers at 28 days after one dose vaccination of CCV (with or without alum) 25 μg / placebo |
| Seroconversion of vibriocidal titers against V. cholerae O1 Inaba and O1 Ogawa after two doses of Euvichol®-Plus in children aged 1 to 4 years | Baseline and at 14 days post two doses of Euvichol®-Plus | Proportion of participants achieving seroconversion of serum vibriocidal antibody titers at 14 days after two doses of Euvichol®-Plus |
| GMT of vibriocidal titers against V. cholerae O1 Inaba and O1 Ogawa after two doses of Euvichol®-Plus in children aged 1 to 4 years | Baseline and at 14 days after two doses of Euvichol®-Plus | GMT of serum vibriocidal antibody titers at 14 days after two doses of Euvichol®-Plus compared to baseline |
| Seroconversion of Serum OSP IgG antibody titers against V. cholerae O1 Inaba after one dose vaccination of CCV 25 μg (with or without alum) in adults (aged 18 to 45 years) and in children (aged 1 to 17 years). | Baseline and at 28 days post the first dose of either CCV with alum, CCV without alum or placebo | Proportion of participants achieving seroconversion (defined as at least 4-fold increase from baseline) of serum OSP IgG antibody titers at 28 days after one dose vaccination of CCV (with or without alum) 25 μg / placebo |
| GMT of Serum OSP IgG antibody titers to V. cholerae O1 Inaba and O1 Ogawa after one dose of CCV 25 μg (with or without alum) in adults (aged 18 to 45 years) and in children (aged 1 to 17 years) | Baseline and at 28 days post the first dose of either CCV with alum, CCV without alum or placebo | \- GMT of serum OSP IgG antibody titers at 28 days after one dose vaccination of CCV (with or without alum) 25 μg / placebo |
| Seroconversion of OSP IgG titers against V. cholerae O1 Inaba and O1 Ogawa after two doses of Euvichol®-Plus in children aged 1 to 4 years | Baseline and at 14 days post two doses of Euvichol®-Plus | Proportion of participants achieving seroconversion of serum OSP IgG antibody titers at 14 days after two doses of Euvichol®-Plus |
| GMT of OSP IgG titers against V. cholerae O1 Inaba and O1 Ogawa after two doses of Euvichol®-Plus in children aged 1 to 4 years: | Baseline and at 14 days after two doses of Euvichol®-Plus | GMT of serum OSP IgG antibody titers at 14 days after two doses of Euvichol®-Plus compared to baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serious adverse events (SAEs) and adverse events of special interest (AESIs) and medically attended adverse event (MAAE) | through study completion, an average of 6 months | Occurrence of any SAE / AESI / MAAE from the first dose vaccination throughout the final study visit |
| Immediate adverse events | Within 30 minutes post each dose | Occurrence of immediate adverse events within 30 minutes after each dose vaccination |
| Solicited adverse events | Within 7 days post each dose | Occurrence of solicited injection site and solicited systemic adverse events from the time of each study vaccination through 7 days after each study vaccination |
| Unsolicited adverse events | Within 28 days post each dose | Occurrence of unsolicited adverse events from the time of each study vaccination through 28 days after each study vaccination. |
| Seroconversion of Serum vibriocidal antibody titers responses to V. cholerae O1 Inaba and O1 Ogawa at 28 days after two doses of CCV 25 μg (with or without alum) / placebo in adults (aged 18 to 45 years) and in children (aged 1 to 17 years. | Baseline and at 28 days post the second dose of either CCV with alum, CCV without alum or placebo | \- Proportion of participants achieving seroconversion of serum vibriocidal antibody titers at 28 days after two doses of CCV 25 μg (with or without alum) / placebo |
| Seroconversion of IgG antibody responses to OSP against V. cholerae O1 Inaba at 28 days after two doses of CCV 25 μg (with or without alum).or placebo in adults (aged 18 to 45 years) and in children (aged 1 to 17 years. | Baseline and at 28 days post the second dose of either CCV with alum, CCV without alum or placebo] | \- Proportion of participants achieving seroconversion of serum anti-OSP IgG antibody titer at 28 days after two doses of CCV (with or without alum) 25 μg or placebo |
| Seroconversion of Serum vibriocidal antibody titers against V. cholerae O1 Inaba and O1 Ogawa at 28 days after booster dose in heterologous boosting group of CCV with or without alum 25 μg and Euvichol®-Plus in children aged 1 to 4 years | Baseline and at 28 days post the heterologous booster dose | \- Proportion of participants achieving seroconversion of serum vibriocidal antibody titers after the heterologous booster dose |
| Seroconversion of IgG antibody responses to OSP against V. cholerae O1 Inaba at 28 days after booster dose in heterologous boosting group of CCV with or without alum 25 μg and Euvichol®-Plus in children aged 1 to 4 years | Baseline and at 28 days post the heterologous booster dose | \- Proportion of participants achieving seroconversion of serum vibriocidal antibody titers after the heterologous booster dose |
| GMT of Serum vibriocidal antibody titers responses to V. cholerae O1 Inaba and O1 Ogawa at 28 days after two doses of CCV 25 μg (with or without alum) / placebo in adults (aged 18 to 45 years) and in children (aged 1 to 17 years. | Baseline and at 28 days post the second dose of either CCV with alum, CCV without alum or placebo | GMT of serum vibriocidal antibody titers at 28 days after two doses of CCV 25 μg (with or without alum) / placebo |
| GMT of IgG antibody responses to OSP against V. cholerae O1 Inaba at 28 days after two doses of CCV 25 μg (with or without alum).or placebo in adults (aged 18 to 45 years) and in children (aged 1 to 17 years. | Baseline and at 28 days post the second dose of either CCV with alum, CCV without alum or placebo] | GMT of serum anti-OSP IgG antibody titer at 28 days after two doses of CCV (with or without alum) 25 μg or placebo |
| GMT of Serum vibriocidal antibody titers against V. cholerae O1 Inaba and O1 Ogawa at 28 days after booster dose in heterologous boosting group of CCV with or without alum 25 μg and Euvichol®-Plus in children aged 1 to 4 years | Baseline and at 28 days post the heterologous booster dose | GMT of serum vibriocidal antibody titers after the heterologous booster dose |
| GMT of IgG antibody responses to OSP against V. cholerae O1 Inaba at 28 days after booster dose in heterologous boosting group of CCV with or without alum 25 μg and Euvichol®-Plus in children aged 1 to 4 years | Baseline and at 28 days post the heterologous booster dose | GMT of serum vibriocidal antibody titers after the heterologous booster dose |
Countries
Kenya
Contacts
CONTACTNaveena D'Cor, MD
CONTACTTarun Saluja, MD
PRINCIPAL_INVESTIGATORJulia Lynch, MD
International Vaccine Institute
Outcome results
None listed