Age-descending Study to Evaluate the Safety and Immunogenicity of the Cholera Conjugate Vaccine in Adults and Children

A Phase II, Randomized, Controlled, Age-descending Study in Adults and Children to Evaluate the Safety and Immunogenicity of the OSP:rTTHc Cholera Conjugate Vaccine in Cholera-endemic Region

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.

Study Overview

• Status: Recruiting
• Conditions: Cholera Vaccination
• Intervention / Treatment: Biological: OSP:rTTHc CCV 25 ㎍ with Aluminum phosphate; Biological: OSP:rTTHc CCV 25 ㎍ without Aluminum phosphate; Biological: Euvichol®-Plus; Other: Placebo; Biological: CCV with Aluminum, Euvichol®-Plus; Biological: CCV without Aluminum, Euvichol®-Plus

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.

• Study Type: Interventional
• Enrollment (Estimated): 390
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Naveena D'Cor, MD; Phone Number: +82 2 8811 000; Email: naveena.dcor@ivi.int
• Study Contact Backup: Name: Tarun Saluja, MD; Phone Number: +82 2 8811 000; Email: Tarun.Saluja@ivi.int

Study Locations

• Kenya
  • Kenyatta National Hospital Complex
    • Nairobi, Kenyatta National Hospital Complex, Kenya, 19676
      • Recruiting
      • KAVI-Institute of Clinical Research, University
      • Contact: Jaoko Walter Godfrey; Phone Number: +254-727-555-254; Email: wjaoko@kaviuon.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

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/exclusion criteria mentioned above
19. Children below 5 years old with Weight for Height Z score and/or Height for Age Z score of less than -2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OSP:rTTHc CCV 25 ㎍ with Aluminum phosphate; 0.5 mL per dose; dosing schedule/duration: 1 dose or 2 doses at 168-days interval administered intramuscularly	Biological: OSP:rTTHc CCV 25 ㎍ with Aluminum phosphate; OSP:rTTHc Cholera Conjugate with Aluminum phosphate Cohort Arms A1, A3, B1, B3, C1, C3, C10
Experimental: OSP:rTTHc CCV 25 ㎍ without Aluminum phosphate; 0.5 mL per dose; dosing schedule/duration: 1 dose or 2 doses at 168-days interval administered intramuscularly	Biological: OSP:rTTHc CCV 25 ㎍ without Aluminum phosphate; OSP:rTTHc Cholera Conjugate without Aluminum phosphate Cohort Arms A2, A4, B2, B4, C2, C4
Active Comparator: Euvichol®-Plus; 1.5 mL per dose; dosing schedule/duration: 2 doses at 14-days interval administered orally	Biological: Euvichol®-Plus; V. cholerae O1 and O139 bivalent inactivated oral cholera vaccine cohort Arm C6
Placebo Comparator: Isotonic Sodium Chloride injection; 0.5 mL per dose; dosing schedule/duration: 2 doses at 168-days interval administered intramuscularly	Other: Placebo; Sterile 0.9% sodium chloride cohort Arms A5, B5, C5
Experimental: OSP:rTTHc CCV 25 ㎍ with Aluminum phosphate and Euvichol®-Plus; 0.5 mL per dose of CCV administered intramuscularly and 1.5 mL dose of Euvichol®-Plus administered orally at 168-days interval	Biological: CCV with Aluminum, Euvichol®-Plus; OSP:rTTHc CCV 25 # with Aluminum phosphate OSP:rTTHc Cholera Conjugate with Aluminum phosphate; Euvichol®-Plus V. cholerae O1 and O139 bivalent inactivated oral cholera vaccine Cohort Arms C7, C9
Experimental: OSP:rTTHc CCV 25 ㎍ without Aluminum phosphate and Euvichol®-Plus; 0.5 mL per dose of CCV administered intramuscularly and 1.5 mL dose of Euvichol®-Plus administered orally at 168-days interval	Biological: CCV without Aluminum, Euvichol®-Plus; OSP:rTTHc CCV 25 # without Aluminum phosphate OSP:rTTHc Cholera Conjugate without Aluminum phosphate; Euvichol®-Plus V. cholerae O1 and O139 bivalent inactivated oral cholera vaccine Cohort Arms C8, C10

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	- 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	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 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)	- GMT of serum vibriocidal antibody titers at 28 days after one dose vaccination of CCV (with or without alum) 25 μg / placebo	Baseline and at 28 days post the first dose of either CCV with alum, CCV without alum or 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	Proportion of participants achieving seroconversion of serum vibriocidal antibody titers at 14 days after two doses of Euvichol®-Plus	Baseline and at 14 days post 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	GMT of serum vibriocidal antibody titers at 14 days after two doses of Euvichol®-Plus compared to baseline	Baseline and at 14 days after two doses of Euvichol®-Plus
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).	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	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 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)	- GMT of serum OSP IgG antibody titers at 28 days after one dose vaccination of CCV (with or without alum) 25 μg / placebo	Baseline and at 28 days post the first dose of either CCV with alum, CCV without alum or 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	Proportion of participants achieving seroconversion of serum OSP IgG antibody titers at 14 days after two doses of Euvichol®-Plus	Baseline and at 14 days post 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:	GMT of serum OSP IgG antibody titers at 14 days after two doses of Euvichol®-Plus compared to baseline	Baseline and at 14 days after two doses of Euvichol®-Plus

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Solicited adverse events	Occurrence of solicited injection site and solicited systemic adverse events from the time of each study vaccination through 7 days after each study vaccination	Within 7 days post each dose
Unsolicited adverse events	Occurrence of unsolicited adverse events from the time of each study vaccination through 28 days after each study vaccination.	Within 28 days post each dose
Serious adverse events (SAEs) and adverse events of special interest (AESIs) and medically attended adverse event (MAAE)	Occurrence of any SAE / AESI / MAAE from the first dose vaccination throughout the final study visit	through study completion, an average of 6 months
Immediate adverse events	Occurrence of immediate adverse events within 30 minutes after each dose vaccination	Within 30 minutes post each dose
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.	- 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	Baseline and at 28 days post the second dose of either CCV with alum, CCV without alum or 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.	- 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	Baseline and at 28 days post the second dose of either CCV with alum, CCV without alum 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	- Proportion of participants achieving seroconversion of serum vibriocidal antibody titers after the heterologous booster dose	Baseline and at 28 days post 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	- Proportion of participants achieving seroconversion of serum vibriocidal antibody titers after the heterologous booster dose	Baseline and at 28 days post 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.	GMT of serum vibriocidal antibody titers at 28 days after two doses of CCV 25 μg (with or without alum) / placebo	Baseline and at 28 days post the second dose of either CCV with alum, CCV without alum or 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.	GMT of serum anti-OSP IgG antibody titer at 28 days after two doses of CCV (with or without alum) 25 μg or placebo	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 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	GMT of serum vibriocidal antibody titers after the heterologous booster dose	Baseline and at 28 days post 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	GMT of serum vibriocidal antibody titers after the heterologous booster dose	Baseline and at 28 days post the heterologous booster dose

Collaborators and Investigators

• Sponsor: International Vaccine Institute
• Collaborators: Massachusetts General Hospital; EuBiologics Co.,Ltd
• Investigators: Principal Investigator: Julia Lynch, MD, International Vaccine Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 31, 2025
• First Submitted That Met QC Criteria: March 27, 2026
• First Posted (Actual): April 3, 2026

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cholera Vaccine; Cholera Conjugate Vaccine; O Specific Polysaccharide; Recombinant Tetanus Toxoid Heavy Chain Fragment
• Additional Relevant MeSH Terms: Inorganic Chemicals; Elements; Metals, Light; Metals; aluminum phosphate; CCV protocol; Aluminum
• Other Study ID Numbers: IVI CCV 002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No