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

Official 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

Overview

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

• Biological OSP:rTTHc CCV 25 ㎍ with Aluminum phosphate
  OSP:rTTHc Cholera Conjugate with Aluminum phosphate Cohort Arms A1, A3, B1, B3, C1, C3, C10
• Biological OSP:rTTHc CCV 25 ㎍ without Aluminum phosphate
  OSP:rTTHc Cholera Conjugate without Aluminum phosphate Cohort Arms A2, A4, B2, B4, C2, C4
• Biological Euvichol®-Plus
  V. cholerae O1 and O139 bivalent inactivated oral cholera vaccine cohort Arm C6
• Other Placebo
  Sterile 0.9% sodium chloride cohort Arms A5, B5, C5
• Biological CCV 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
• Biological CCV 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

Primary outcome measures

• 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). [Time frame: 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) [Time frame: 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 [Time frame: 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 [Time frame: 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). [Time frame: 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) [Time frame: 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 [Time frame: 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: [Time frame: Baseline and at 14 days after two doses of Euvichol®-Plus]

Secondary outcome measures (12)

• Serious adverse events (SAEs) and adverse events of special interest (AESIs) and medically attended adverse event (MAAE) [Time frame: through study completion, an average of 6 months]
• Immediate adverse events [Time frame: Within 30 minutes post each dose]
• Solicited adverse events [Time frame: Within 7 days post each dose]
• Unsolicited adverse events [Time frame: Within 28 days 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. [Time frame: 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. [Time frame: 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 [Time frame: 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 [Time frame: 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. [Time frame: 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. [Time frame: 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 [Time frame: 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 [Time frame: Baseline and at 28 days post the heterologous booster dose]

Eligibility criteria

Inclusion criteria

• Individuals aged 1 to 45 years at consent
• Participants/ Participants' legally authorized representative (LAR) willing to provide written informed consent to participate in the study voluntarily
• Participants who can comply with the study requirements
• Individuals in good health as determined by the outcome of medical history, physical examination, and the clinical judgment of the investigator

Exclusion criteria

• Known history or allergy to investigational vaccine components or other medications, or any other allergies
• Individuals with major congenital abnormalities
• Known history of immune function disorders including immunodeficiency diseases (known HIV infection¥ or other immune function disorders)
• 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.
• 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
• 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
• Individuals with splenectomy
• Individuals with known bleeding disorders
• Receipt of blood, blood-derived products, or immunoglobulin products in the past 3 months
• 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.
• Individuals with active or known previous Vibrio cholerae infection
• Individuals with a history of severe diarrhea in the last 6 months requiring care at a medical facility lasting 24 hours or more
• Individuals with prior receipt of a cholera vaccine in the last 5 years
• Any female participant who is lactating or pregnant
• 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.
• 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
• Individuals who are research staff involved with the clinical trial or family/household members of research staff
• As per Investigator's medical judgement, an individual could also be excluded from the study despite meeting all inclusion/exclusion criteria mentioned above
• Children below 5 years old with Weight for Height Z score and/or Height for Age Z score of less than -2

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

Kenya · 1 center

• KAVI-Institute of Clinical Research, University — Nairobi

Identifiers

NCT: NCT07509047 · IVI CCV 002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗