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

NCT05559983 | Completed Phase 1 DMC

• 1 other identifier: IVI-CCV-001
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Cholera Vaccination Reaction

Keywords

Cholera Conjugate Vaccine; O Specific Polysaccharide; Recombinant Tetanus Toxoid Heavy Chain Fragment

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (6)

• Seroconversion rates of IgG antibody responses to OSP

  Baseline and at 28 days post the first and second dose

• Geometric Mean Titers (GMTs) of serum anti-OSP IgG

  Baseline and at 28 days post the first and second dose

• Geometric Mean Fold Rise (GMFR) of serum anti-OSP IgG

  At 28 days post the first and second dose

• Seroconversion rates of serum vibriocidal antibody titers

  Baseline and at 28 days post the first and second dose

• GMT of serum vibriocidal antibody titers

  Baseline and at 28 days post the first and second dose

Other Outcomes (2)

• Seroconversion of serum anti-TT antibody titer

  Baseline and at 28 days post the first and second dose

• Memory B Cell responses

  Baseline, 28 days, and 6 months

Study Arms (3)

OSP:rTTHc Cholera Conjugate Vaccine

EXPERIMENTAL

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; Biological: OSP:rTTHc Cholera Conjugate Vaccine Cohort B; Biological: OSP:rTTHc Cholera Conjugate Vaccine Cohort C

OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate adjuvant

EXPERIMENTAL

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; Biological: OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate adjuvant Cohort B; Biological: OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate adjuvant Cohort C

Placebo

PLACEBO COMPARATOR

2 doses @0.5 mL of Sterile 0.9% sodium chloride administered intramuscularly in deltoid region at 4 weeks apart

Other: Placebo Cohort A; Other: Placebo Cohort B; Other: Placebo Cohort C

Interventions

OSP:rTTHc Cholera Conjugate Vaccine Cohort A BIOLOGICAL

OSP:rTTHc Cholera Conjugate Vaccine without Aluminum phosphate with dose formulation 5 µg of OSP:rTTHc

OSP:rTTHc Cholera Conjugate Vaccine

OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate adjuvant Cohort A BIOLOGICAL

OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate with dose formulation 5 µg of OSP:rTTHc

OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate adjuvant

Placebo Cohort A OTHER

Sterile 0.9% sodium chloride

Placebo

OSP:rTTHc Cholera Conjugate Vaccine Cohort B BIOLOGICAL

OSP:rTTHc Cholera Conjugate Vaccine without Aluminum phosphate with dose formulation 10 µg of OSP:rTTHc

OSP:rTTHc Cholera Conjugate Vaccine

OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate adjuvant Cohort B BIOLOGICAL

OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate with dose formulation 10 µg of OSP:rTTHc

OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate adjuvant

Placebo Cohort B OTHER

Sterile 0.9% sodium chloride

Placebo

OSP:rTTHc Cholera Conjugate Vaccine Cohort C BIOLOGICAL

OSP:rTTHc Cholera Conjugate Vaccine without Aluminum phosphate with dose formulation 25 µg of OSP:rTTHc

OSP:rTTHc Cholera Conjugate Vaccine

OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate adjuvant Cohort C BIOLOGICAL

OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate with dose formulation 25 µg of OSP:rTTHc

OSP:rTTHc Cholera Conjugate Vaccine with Aluminum phosphate adjuvant

Placebo Cohort C OTHER

Sterile 0.9% sodium chloride

Placebo

Eligibility Criteria

• Age: 19 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy Korean participants aged 19 to 45 years at consent
• Participants willing to provide written informed consent to participate study voluntarily
• Participants who can be followed up during the study period and can comply with the study requirements
• Individual in good health as determined by the outcome of medical history, physical examination, laboratory evaluations and the clinical judgment of the investigator
• Females of childbearing potential with negative pregnancy test result on the day of screening
• 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.
• Males who agree to use an effective birth control method\* from the screening and up to 12 weeks after the second dose vaccination

You may not qualify if:

• 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
• Individuals with major congenital abnormalities which in the opinion of investigator may affect the participant's participation in the study
• 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.
• 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 a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time resulting in contraindication for intramuscular injections/blood extractions
• 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
• Body mass index (BMI) ≥ 35 kg/m2
• Individuals with active or previous Vibrio cholerae infection
• Individuals with history of severe diarrhea requiring hospitalization or emergency room visit for the last 5 years
• Individuals with receipt of a cholera vaccine
• Individuals who lived in cholera endemic areas for more than 6 months for the past 10 years
• Any female participant who is lactating\*, pregnant or planning for pregnancy\*\* during study period

Sponsors & Collaborators

• International Vaccine Institute: lead
• EuBiologics Co.,Ltd: collaborator
• Massachusetts General Hospital: collaborator

Study Sites (3)

The Catholic University of Korea Seoul St. Mary's Hospital

Seoul, 06591, South Korea

Location

CHA Bundang Medical Center (CBMC) of CHA University

Seoul, 08826, South Korea

Location

Soon Chun Hyang University Hospital

Seoul, 08826, South Korea

Location

Related Publications (2)

• Kelly M, Janardhanan J, Wagh C, Verma S, Charles RC, Leung DT, Kamruzzaman M, Pansuriya RK, Chowdhury F, Vann WF, Kaminski RW, Khan AI, Bhuiyan TR, Qadri F, Kovac P, Xu P, Ryan ET. Development of a Shigella conjugate vaccine targeting Shigella flexneri 6 that is immunogenic and provides protection against virulent challenge. Vaccine. 2024 Oct 24;42(24):126263. doi: 10.1016/j.vaccine.2024.126263. Epub 2024 Aug 31.

  PMID: 39217775 DERIVED

• Kelly M, Jeon S, Yun J, Lee B, Park M, Whang Y, Lee C, Charles RC, Bhuiyan TR, Qadri F, Kamruzzaman M, Cho S, Vann WF, Xu P, Kovac P, Ganapathy R, Lynch J, Ryan ET. Vaccination of Rabbits with a Cholera Conjugate Vaccine Comprising O-Specific Polysaccharide and a Recombinant Fragment of Tetanus Toxin Heavy Chain Induces Protective Immune Responses against Vibrio cholerae O1. Am J Trop Med Hyg. 2023 Oct 2;109(5):1122-1128. doi: 10.4269/ajtmh.23-0259. Print 2023 Nov 1.

  PMID: 37783453 DERIVED

Study Officials

• Anh Wartel, MD

  +82 2 8811 274

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study investigators, study nurse, and those assessing clinical outcomes, and laboratory analysis will be blinded to investigational product allocation until database lock for the final analysis.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The first fifty participant in the study will be enrolled into cohort A and receive low antigen product with or without adjuvant, or placebo. The Safety Monitoring Committee (SMC) and the independent Data Safety Monitoring Board (DSMB) will review the safety data collected through seven days after the second dose vaccination of the cohort A before the study enrollment can progress to cohort B (middle dose). Dose escalation to cohort C (high dose) will follow the same procedures.

Study Record Dates

• First Submitted: September 21, 2022
• First Posted: September 29, 2022
• Study Start: December 5, 2022
• Primary Completion: September 8, 2023
• Study Completion: January 23, 2024
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (3)