dose escalation study to evaluate the safety and immunogenicity of the cholera conjugate vaccine in healthy adults

Conditions: Cholera Vaccination Reaction

Summary: this phase i, first-in-human study is intended to primarily determine the safety of the dose range with or without aluminum phosphate adjuvant expected to be needed for later clinical studies, to determine the nature of adverse reactions (i.e., safety profile) and to secondly assess the aluminum phosphate humoral immune responses in non-endemic population to guide future dose selection.

a total of 150 eligible participants will be recruited in 3 sequential dose cohorts: low-dose 5 µg, medium-dose 10 µg, and high-dose 25 µg. in each dose cohorts, the participants will be randomized in a blinded manner into three arms (vaccine antigen with aluminum phosphate, vaccine antigen without aluminum phosphate or placebo) in 2:2:1 ratio. all the participants will receive two intramuscular injections of 0.5 ml of the designated study vaccine or placebo on deltoid muscle, on days 0 and 28. the dsmb will review the safety data and approve dose escalation before investigational product injection of the next cohort is initiated. the study primary objective is to evaluate the safety of the o specific polysaccharide recombinant tetanus toxoid heavy chain fragment (osp:rtthc) cholera conjugate vaccine (ccv) after each dose vaccination. the secondary objectives are: * to evaluate the antibody response to osp igg against v. cholerae o1 after each dose vaccination of osp:rtthc ccv/placebo compared to pre-vaccination. * to evaluate the serum vibriocidal antibody titers against v. cholerae o1 inaba and v. cholerae o1 ogawa 4 weeks after each dose vaccination of osp:rtthc ccv/placebo compared to pre-vaccination. the exploratory objectives are: * to describe the anti tetanus toxoid (anti-tt) immunoglobulin g (igg) 4 weeks after each dose vaccination of osp:rtthc ccv/placebo compared to pre-vaccination. * to describe memory b cell responses 4 and 28 weeks after first dose vaccination of osp:rtthc ccv/placebo compared to pre-vaccination.

Eligibility criteria:
inclusion criteria: 1. healthy korean participants aged 19 to 45 years at consent 2. participants willing to provide written informed consent to participate study voluntarily 3. participants who can be followed up during the study period and can comply with the study requirements 4. individual in good health as determined by the outcome of medical history, physical examination, laboratory evaluations and the clinical judgment of the investigator 5. females of childbearing potential with negative pregnancy test result on the day of screening 6. females of childbearing potential who agree to use an effective birth control method\* from the screening and p to 12 weeks after the second dose vaccination. 7. males who agree to use an effective birth control method\* from the screening and up to 12 weeks after the second dose vaccination exclusion criteria: 1. known history or allergy to investigational vaccine components and/or excipients or other medications, or any other allergies deemed by the investigator to increase the risk of an adverse event if they were to participate in the trial 2. individuals with major congenital abnormalities which in the opinion of investigator may affect the participant's participation in the study 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. 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 6. individuals with splenectomy 7. individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time resulting in contraindication for intramuscular injections/blood extractions 8. receipt of blood, blood-derived products, or immunoglobulin products in the past 3 months 9. 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 10. body mass index (bmi) ≥ 35 kg/m2 11. individuals with active or previous vibrio cholerae infection 12. individuals with history of severe diarrhea requiring hospitalization or emergency room visit for the last 5 years 13. individuals with receipt of a cholera vaccine 14. individuals who lived in cholera endemic areas for more than 6 months for the past 10 years 15. as per investigator's medical judgement, an individual could be excluded from the study despite meeting all inclusion/exclusion criteria mentioned above 16. any female participant who is lactating\*, pregnant or planning for pregnancy\*\* during study period 17. individuals enrolled in another clinical trial or bioequivalence test during 6 months prior to enrollment, concomitantly enrolled or scheduled to be enrolled in another trial 18. individuals who are research staff involved with the clinical study or family/household members of research staff

Keywords: cholera conjugate vaccine o specific polysaccharide recombinant tetanus toxoid heavy chain fragment