Pharmacy and Poisons Board: Applications

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Protocol No:

ECCT/25/05/13

Date of Protocol:

09-04-2025

Study Title:	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
Study Objectives:	Primary Objectives To evaluate the serum vibriocidal antibody titers against V. cholerae O1 Inaba and O1 Ogawa at 4 weeks after one dose of CCV (with or without alum) 25 μg / placebo in adults (aged 18 to 45 years) and in children (aged 5 to 17 years) compared to pre-vaccination. To evaluate the serum vibriocidal antibody titers against V. cholerae O1 Inaba and O1 Ogawa at 4 weeks after one dose of CCV (with or without alum) 25 μg / placebo or at 2 weeks after two doses of Euvichol®-Plus in children (aged 1 to 4 years) compared to pre-vaccination. To evaluate the OSP IgG antibody titers using ELISA, against V. cholerae O1 Inaba at 4 weeks after one dose of CCV (with or without alum) 25 μg / placebo in adults (aged 18 to 45 years) and in children (aged 5 to 17 years) compared to pre-vaccination. To evaluate the OSP IgG antibody titers using ELISA, against V. cholerae O1 Inaba at 4 weeks after one dose of CCV (with or without alum) 25 μg / placebo or at 2 weeks after two doses of Euvichol®-Plus in children (aged 1 to 4 years) compared to pre-vaccination. Secondary Objective To evaluate the serum vibriocidal antibody titers against V. cholerae O1 Inaba and O1 Ogawa at 4 weeks after two doses of CCV (with or without alum) 25 μg / placebo in adults (aged 18 to 45 years) and in children (aged 1 to 17 years) compared to pre-vaccination. To evaluate the serum vibriocidal antibody titers against V. cholerae O1 Inaba and O1 Ogawa at 4 weeks after each dose in heterologous boosting group of CCV with or without alum 25 μg (1st dose) and Euvichol®-Plus (2nd dose) or Euvichol®-Plus (1st dose) and CCV with or without alum 25 μg (2nd dose) in children (aged 1 to 4 years). To evaluate the OSP IgG antibody titers using ELISA, against V. cholerae O1 Inaba at 4 weeks after two doses of CCV (with or without alum) 25 μg / placebo in adults (aged 18 to 45 years) and in children (aged 1 to 17 years) compared to pre-vaccination. To evaluate the OSP IgG antibody titers using ELISA, against V. cholerae O1 Inaba at 4 weeks after heterologous booster dose of CCV 25 μg with or without alum (with Euvichol®-Plus as the 1st dose) or of Euvichol®-Plus (with CCV 25 μg with or without alum as the 1st dose) in children (aged 1 to 4 years) compared to pre-vaccination. To evaluate the safety of CCV (with or without alum) 25 μg after one and two doses of vaccination in adults (aged 18 to 45 years) and in children (aged 1 to 17 years; cohorts B and C combined as well as individually). Exploratory Objectives To describe the anti-TT IgG at 4 weeks after each dose of CCV (with or without alum) 25 μg in adults (aged 18 to 45 years) and in subset of children (aged 1 to 17 years; subset of cohorts B and C combined as well as individually) compared to pre-vaccination. To describe the serum vibriocidal antibody titers against V. cholerae O1 Inaba and O1 Ogawa at 6 months after one dose of CCV 25 μg / placebo in adults (aged 18 to 45 years) and in children (aged 1 to 17 years; cohorts B and C combined as well as individually) compared to pre-vaccination. To describe the serum vibriocidal antibody titers against V. cholerae O1 Inaba and O1 Ogawa at 6 months after two doses of Euvichol®-Plus in children (aged 1 to 4 years) compared to pre-vaccination. To describe the OSP IgA and IgM antibody titers using ELISA, against V. cholerae O1 Inaba at 4 weeks after each dose of CCV (with or without alum) 25 μg in adults (aged 18 to 45 years) and in subset of children (aged 1 to 17 years; subset of cohorts B and C combined as well as individually) compared to pre-vaccination. To describe the OSP IgG, IgA and IgM using LUMINEX, antibody titers against V. cholerae O1 Inaba at 4 weeks after each dose of CCV (with or without alum) 25 μg in adults (aged 18 to 45 years) and in subset of children (aged 1 to 17 years; subset of cohorts B and C combined as well as individually) compared to pre-vaccination. To describe the OSP IgA and IgM using ELISA, antibody titers against V. cholerae O1 Inaba at 2 weeks after two doses of Euvichol®-Plus in subset of children (aged 1 to 4 years) compared to pre-vaccination. To describe the OSP IgG, IgA and IgM using LUMINEX, antibody titers against V. cholerae O1 Inaba at 2 weeks after two doses of Euvichol®-Plus in subset of children (aged 1 to 4 years) compared to pre-vaccination. To describe the OSP IgG antibody titers using ELISA, against V. cholerae O1 Inaba at 6 months after one dose of CCV (with or without alum) 25 μg in adults (aged 18 to 45 years) and in children (aged 1 to 17 years; cohorts B and C combined as well as individually) compared to pre-vaccination. To describe the OSP IgA and IgM antibody titers using ELISA, against V. cholerae O1 Inaba at 6 months after one dose of CCV (with or without alum) 25 μg in adults (aged 18 to 45 years) and in subset of children (aged 1 to 17 years; cohorts B and C combined as well as individually) compared to pre-vaccination. To describe the OSP IgG antibody titers using ELISA, against V. cholerae O1 Inaba at 6 months after two doses of Euvichol®-Plus in children (aged 1 to 4 years) compared to pre-vaccination. To describe the OSP IgA and IgM antibody titers using ELISA, against V. cholerae O1 Inaba at 6 months after two doses of Euvichol®-Plus in subset of children (aged 1 to 4 years) compared to pre-vaccination. To describe the OSP IgG, IgA and IgM using LUMINEX, antibody titers against V. cholerae O1 Inaba at 6 months after one dose of CCV (with or without alum) 25 μg in adults (aged 18 to 45 years) and in subset of children (aged 1 to 17 years; cohorts B and C combined as well as individually) compared to pre-vaccination. To describe the OSP IgG, IgA and IgM using LUMINEX, antibody titers against V. cholerae O1 Inaba at 6 months after two doses of Euvichol-Plus® in subset of children (aged 1 to 4 years) compared to pre-vaccination. To describe OSP-specific IgG and, IgA memory B cell responses at 4- and 24- weeks after one dose of CCV 25 μg in adults (aged 18 to 45 years) compared to pre-vaccination.
Laymans Summary:	The introduction of oral cholera vaccine (OCV) and its use in mass vaccination campaigns have proved a game-changer in the fight against cholera. A two dose OCV regimen works to prevent cholera for three to five years by effectively bridging emergency response and longer-term cholera control with a water, sanitation and hygiene (WASH) focus, demonstrating that cholera is not inevitable and that cholera control is not beyond reach. However, two dose OCV is poorly protective in young children who bear a large burden of cholera in endemic countries. We believe that a cholera conjugate vaccine will provide the desired characteristics of inducing an effective and lasting immune response across a wide age range including young children and provide a low cost and sustainable tool to end cholera. With a more effective response in young children, a conjugate vaccine can be incorporated into routine early childhood immunization programs providing early and direct protection to the age group with the highest burden of disease. 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 a cholera-endemic region.
Abstract of Study:	The introduction of oral cholera vaccine (OCV) and its use in mass vaccination campaigns have proved a game-changer in the fight against cholera. A two dose OCV regimen works to prevent cholera for three to five years by effectively bridging emergency response and longer-term cholera control with a water, sanitation and hygiene (WASH) focus, demonstrating that cholera is not inevitable and that cholera control is not beyond reach. However, two dose OCV is poorly protective in young children who bear a large burden of cholera in endemic countries. We believe that a cholera conjugate vaccine will provide the desired characteristics of inducing an effective and lasting immune response across a wide age range including young children and provide a low cost and sustainable tool to end cholera. With a more effective response in young children, a conjugate vaccine can be incorporated into routine early childhood immunization programs providing early and direct protection to the age group with the highest burden of disease. We plan to conduct a phase II clinical trial to determine the immunogenicity and safety of single dose and two doses of OSP:rTTHc cholera conjugate vaccine (CCV) with or without alum adjuvant. 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). KAVI-Institute of Clinical Research will recruit and enrol 390 participants from within Nairobi City County. 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.