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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 390
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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:
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
The study in cohort A and B will be conducted in an observer blinded manner. Observer-blind means only the designated study site personnel responsible for investigational product preparation will be aware of the investigational product allocation while all other individuals involved in the study (study participants, study investigators, study nurses, and all personnel assessing clinical outcomes) will be blinded to investigational product allocation until final database lock. The study in cohort C will be conducted mostly in an observer blinded manner i.e., the blind will be maintained between arms C1 to C5, between C7 and C8, and between C9 and C10, but will be partially open label (where blinding is not feasible due to the different routes of administration of assigned IP) between the different type of arms i.e. those receiving CCV (C1-5) vs comparator (C6) vs heterologous arms (C7-8 vs C9-10).
入排标准
- 年龄范围
- 1 Year 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Isotonic Sodium Chloride injection
0.5 mL per dose; dosing schedule/duration: 2 doses at 168-days interval administered intramuscularly
干预措施: Placebo (Other)
OSP:rTTHc CCV 25 ㎍ with Aluminum phosphate
0.5 mL per dose; dosing schedule/duration: 1 dose or 2 doses at 168-days interval administered intramuscularly
干预措施: OSP:rTTHc CCV 25 ㎍ with Aluminum phosphate (Biological)
OSP:rTTHc CCV 25 ㎍ without Aluminum phosphate
0.5 mL per dose; dosing schedule/duration: 1 dose or 2 doses at 168-days interval administered intramuscularly
干预措施: OSP:rTTHc CCV 25 ㎍ without Aluminum phosphate (Biological)
Euvichol®-Plus
1.5 mL per dose; dosing schedule/duration: 2 doses at 14-days interval administered orally
干预措施: Euvichol®-Plus (Biological)
OSP:rTTHc CCV 25 ㎍ with Aluminum phosphate and Euvichol®-Plus
0.5 mL per dose of CCV administered intramuscularly and 1.5 mL dose of Euvichol®-Plus administered orally at 168-days interval
干预措施: CCV with Aluminum, Euvichol®-Plus (Biological)
OSP:rTTHc CCV 25 ㎍ without Aluminum phosphate and Euvichol®-Plus
0.5 mL per dose of CCV administered intramuscularly and 1.5 mL dose of Euvichol®-Plus administered orally at 168-days interval
干预措施: CCV without Aluminum, Euvichol®-Plus (Biological)
结局指标
主要结局
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
时间窗: Baseline and at 14 days post two doses of Euvichol®-Plus
Proportion of participants achieving seroconversion of serum OSP IgG antibody titers at 14 days after 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:
时间窗: Baseline and at 14 days after two doses of Euvichol®-Plus
GMT of serum OSP IgG antibody titers at 14 days after two doses of Euvichol®-Plus compared to baseline
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).
时间窗: Baseline and at 28 days post the first dose of either CCV with alum, CCV without alum or placebo
\- Proportion of participants achieving seroconversion (defined as at least 4-fold increase from baseline) of serum vibriocidal antibody titers at 28 days after one dose vaccination of CCV (with or without alum) 25 μg / 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)
时间窗: 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 at 28 days after one dose vaccination of CCV (with or without alum) 25 μg / 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
时间窗: Baseline and at 14 days post two doses of Euvichol®-Plus
Proportion of participants achieving seroconversion of serum vibriocidal antibody titers at 14 days after 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
时间窗: Baseline and at 14 days after two doses of Euvichol®-Plus
GMT of serum vibriocidal antibody titers at 14 days after two doses of Euvichol®-Plus compared to baseline
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).
时间窗: Baseline and at 28 days post the first dose of either CCV with alum, CCV without alum or placebo
Proportion of participants achieving seroconversion (defined as at least 4-fold increase from baseline) of serum OSP IgG antibody titers at 28 days after one dose vaccination of CCV (with or without alum) 25 μg / 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)
时间窗: 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 at 28 days after one dose vaccination of CCV (with or without alum) 25 μg / placebo
次要结局
- Serious adverse events (SAEs) and adverse events of special interest (AESIs) and medically attended adverse event (MAAE)(through study completion, an average of 6 months)
- Solicited adverse events(Within 7 days post each dose)
- Unsolicited adverse events(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.(Baseline and at 28 days post the second dose of either CCV with alum, CCV without alum or placebo)
- Immediate adverse events(Within 30 minutes post each dose)
- 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.(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(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(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.(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.(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(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(Baseline and at 28 days post the heterologous booster dose)