Dose Escalation Study to Evaluate the Safety and Immunogenicity of the Cholera Conjugate Vaccine in Healthy Adults

A Phase I, Multicenter, Observer-Blinded, Randomized, Placebo-Controlled, Dose Escalation Trial to Evaluate the Safety and Immunogenicity of the OSP:rTTHc Cholera Conjugate Vaccine in 19 to 45 Years Old Healthy Korean Participants

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.

Study Overview

• Status: Recruiting
• Conditions: Cholera Vaccination Reaction
• Intervention / Treatment: Biological: OSP:rTTHc Cholera Conjugate Vaccine Cohort A; Biological: OSP:rTTHc Cholera Conjugate Vaccine Cohort B; Biological: OSP:rTTHc Cholera Conjugate Vaccine Cohort C; Biological: OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate adjuvant Cohort A; Biological: OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate adjuvant Cohort B; Biological: OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate adjuvant Cohort C; Other: Placebo Cohort A; Other: Placebo Cohort B; Other: Placebo Cohort C

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Naveena Aloysia D'Cor, MD; Phone Number: +82 2 8811 000; Email: Naveena.DCor@ivi.int
• Study Contact Backup: Name: Anh Wartel, MD; Phone Number: +82 2 8811 274; Email: Anh.Wartel@ivi.int

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • The Catholic University of Korea Seoul St. Mary's Hospital
    • Contact: Dong Gun Lee, MD, PhD; Email: symonlee@catholic.ac.kr
    • Principal Investigator: Professor Dong Gun Lee, MD, PhD
  • Seoul, Korea, Republic of, 08826
    • Recruiting
    • CHA Bundang Medical Center (CBMC) of CHA University
    • Contact: Anhye Kim, MD, PhD; Email: ahkim1@cha.ac.kr
    • Principal Investigator: Anhye Kim, MD, PhD
  • Seoul, Korea, Republic of, 08826
    • Recruiting
    • Soon Chun Hyang University Hospital
    • Contact: Jong Tak Jung, MD, PhD; Email: unsymmetry@gmail.com
    • Principal Investigator: Jong Tak Jung, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OSP:rTTHc Cholera Conjugate Vaccine; 2 doses @0.5 mL of test vaccine administered intramuscularly in deltoid region at 4 weeks apart	Biological: OSP:rTTHc Cholera Conjugate Vaccine Cohort A; OSP:rTTHc Cholera Conjugate Vaccine without Aluminum phosphate with dose formulation 5 µg of OSP:rTTHc; Biological: OSP:rTTHc Cholera Conjugate Vaccine Cohort B; OSP:rTTHc Cholera Conjugate Vaccine without Aluminum phosphate with dose formulation 10 µg of OSP:rTTHc; Biological: OSP:rTTHc Cholera Conjugate Vaccine Cohort C; OSP:rTTHc Cholera Conjugate Vaccine without Aluminum phosphate with dose formulation 25 µg of OSP:rTTHc
Experimental: OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate adjuvant; 2 doses @0.5 mL of test vaccine administered intramuscularly in deltoid region at 4 weeks apart	Biological: OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate adjuvant Cohort A; OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate with dose formulation 5 µg of OSP:rTTHc; Biological: OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate adjuvant Cohort B; OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate with dose formulation 10 µg of OSP:rTTHc; Biological: OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate adjuvant Cohort C; OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate with dose formulation 25 µg of OSP:rTTHc
Placebo Comparator: Placebo; 2 doses @0.5 mL of Sterile 0.9% sodium chloride administered intramuscularly in deltoid region at 4 weeks apart	Other: Placebo Cohort A; Sterile 0.9% sodium chloride; Other: Placebo Cohort B; Sterile 0.9% sodium chloride; Other: Placebo Cohort C; Sterile 0.9% sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious adverse events (SAEs) and adverse events of special interest (AESIs)	Occurrence of any SAEs/AESIs from the time of the first dose of study vaccine	Entire study participation period (approximately 7 months)
Immediate adverse events	Occurrence of immediate adverse events within 30 minutes from the time of each study vaccination.	Within 30 minutes post each dose
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
Clinical safety laboratory parameters	Occurrence of clinically significant changes in clinical safety laboratory parameters from the time of each vaccination through 28 days after each study vaccination.	Within 28 days post each dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion rates of IgG antibody responses to OSP	Proportion of participants achieving seroconversion (defined as a 4-fold increase of serum anti-OSP IgG antibody titer at approximately 28 days after the first and second dose of investigational product compared to baseline	Baseline and at 28 days post the first and second dose
Geometric Mean Titers (GMTs) of serum anti-OSP IgG	GMTs of serum anti-OSP IgG antibodies at 28 days after the first and second dose of investigational product compared to baseline	Baseline and at 28 days post the first and second dose
Geometric Mean Fold Rise (GMFR) of serum anti-OSP IgG	GMFR of serum anti-OSP IgG antibodies at 28 days after the first and second dose of investigational product	At 28 days post the first and second dose
Seroconversion rates of serum vibriocidal antibody titers	Proportion of participants with a 4-fold or greater rises in serum vibriocidal antibody titers against V. cholerae O1 Inaba and V. cholerae O1 Ogawa, relative to baseline, 28 days after the first and second dose of investigational product compared to baseline	Baseline and at 28 days post the first and second dose
GMT of serum vibriocidal antibody titers	Geometric Mean Titers (GMT) of serum vibriocidal antibody titers against V. cholerae O1 Inaba and V. cholerae O1 Ogawa at 28 days after the first and second dose of investigational product compared to baseline .	Baseline and at 28 days post the first and second dose
GMFR of serum vibriocidal antibody titers	GMFR of serum vibriocidal antibody titers against V. cholerae O1 Inaba and V. cholerae O1 Ogawa at 28 days after the first and second dose of investigational product	At 28 days post the first and second dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion of serum anti-TT antibody titer	Proportion of participants achieving seroconversion (defined as at least 4-fold increase) of serum anti-TT antibody titer at 28 days after first and second dose vaccination compared to baseline	Baseline and at 28 days post the first and second dose
Memory B Cell responses	Memory B Cell responses measured by Elispot assay at 28 days after the first dose vaccination and 6 months after second dose vaccination compared to baseline.	Baseline, 28 days, and 6 months

Collaborators and Investigators

• Sponsor: International Vaccine Institute
• Collaborators: Massachusetts General Hospital; EuBiologics Co.,Ltd
• Investigators: Principal Investigator: Anh Wartel, MD, +82 2 8811 274

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2022
• Primary Completion (Anticipated): July 31, 2023
• Study Completion (Anticipated): January 31, 2024

Study Registration Dates

• First Submitted: September 21, 2022
• First Submitted That Met QC Criteria: September 28, 2022
• First Posted (Actual): September 29, 2022

Study Record Updates

• Last Update Posted (Estimate): March 3, 2023
• Last Update Submitted That Met QC Criteria: March 1, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Cholera Conjugate Vaccine; O Specific Polysaccharide; Recombinant Tetanus Toxoid Heavy Chain Fragment
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Vibrio Infections; Cholera; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunologic Factors; Gastrointestinal Agents; Adjuvants, Immunologic; Antacids; Vaccines; Aluminum phosphate
• Other Study ID Numbers: IVI-CCV-001

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