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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 150
- 试验地点
- 3
- 主要终点
- Immediate adverse events
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 19 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
- •As per Investigator's medical judgement, an individual could be excluded from the study despite meeting all inclusion/exclusion criteria mentioned above
- •Any female participant who is lactating*, pregnant or planning for pregnancy** during study period
- •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
- •Individuals who are research staff involved with the clinical study or family/household members of research staff
研究组 & 干预措施
Placebo
2 doses @0.5 mL of Sterile 0.9% sodium chloride administered intramuscularly in deltoid region at 4 weeks apart
干预措施: Placebo Cohort A (Other)
Placebo
2 doses @0.5 mL of Sterile 0.9% sodium chloride administered intramuscularly in deltoid region at 4 weeks apart
干预措施: Placebo Cohort B (Other)
Placebo
2 doses @0.5 mL of Sterile 0.9% sodium chloride administered intramuscularly in deltoid region at 4 weeks apart
干预措施: Placebo Cohort C (Other)
结局指标
主要结局
Immediate adverse events
时间窗: Within 30 minutes post each dose
Occurrence of immediate adverse events within 30 minutes from the time of each study vaccination.
Solicited adverse events
时间窗: Within 7 days post each dose
Occurrence of solicited injection site and solicited systemic adverse events from the time of each study vaccination through 7 days after each study vaccination
Unsolicited adverse events
时间窗: Within 28 days post each dose
Occurrence of unsolicited adverse events from the time of each study vaccination through 28 days after each study vaccination.
Serious adverse events (SAEs) and adverse events of special interest (AESIs)
时间窗: Entire study participation period (approximately 7 months)
Occurrence of any SAEs/AESIs from the time of the first dose of study vaccine
Clinical safety laboratory parameters
时间窗: Within 28 days post each dose
Occurrence of clinically significant changes in clinical safety laboratory parameters from the time of each vaccination through 28 days after each study vaccination.
次要结局
- Geometric Mean Titers (GMTs) of serum anti-OSP IgG(Baseline and at 28 days post the first and second dose)
- Seroconversion rates of IgG antibody responses to OSP(Baseline and 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)
- Geometric Mean Fold Rise (GMFR) of serum anti-OSP IgG(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)
- GMFR of serum vibriocidal antibody titers(At 28 days post the first and second dose)