Phase I/III, Multicenter, Observer-Blinded, Randomized, Active Controlled Trial to Evaluate Immunogenicity Non-Inferiority, Safety and Lot-to-Lot Consistency of Biovac OCV-S to Euvichol®-Plus in 1 to 45 Years Old South Africans
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 2,824
- 试验地点
- 5
- 主要终点
- Seroconversion of vibriocidal titers against Vibrio cholerae O1 Inaba and O1 Ogawa
研究概览
简要总结
This Phase I/III clinical trial is intended to establish the immunogenicity and safety profile of Biovac OCV-S compared to available WHO pre-qualified vaccine Euvichol®-Plus in healthy adults and children and in adult people living with HIV (PLWH). The lot-to-lot consistency of Biovac OCV-S in healthy adults will also be determined.
详细描述
This is a phase I/III, multicenter, observer-blinded, age-descending, randomized, active controlled trial being conducted in South Africa to evaluate the immunogenicity non-inferiority and safety of Biovac OCV-S compared to Euvichol®-Plus among adults and children, and to evaluate the lot-to-lot consistency of Biovac OCV-S in adults.
A total of 2824 participants aged 1-45 years will be enrolled in the study in 4 cohorts: cohort A (1272 healthy adults aged 18-45 years), cohort AA (160 people living with HIV (PLWH) aged 18-45 years), cohort B (696 healthy children aged 6-17 years), and cohort C (696 healthy children aged 1-5 years). Participants in cohort A will be randomized into 4 arms to receive either one of the 3 lots of Biovac OCV-S or to receive the comparator Euvichol®-Plus in 1:1:1:1 ratio. Participants in cohorts AA, B and C will each be randomized into 2 arms to receive either Biovac OCV-S or Euvichol®-Plus in 3:1 ratio.
Each of the study participants will receive the assigned investigational product Biovac OCV-S or Euvichol®-Plus given orally in 2 doses at 2 weeks interval and will be followed up for safety and immunogenicity at specific time points. Each participant will be in the study for approximately 27 weeks.
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)
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
- •Inclusion Criteria (for healthy/HIV-negative cohorts A, B and C)
- •Healthy participants aged 1 to 45 years at consent
- •Participants/Parent(s)/Legally Authorized Representative (LAR) willing to provide informed consent/assent
- •HIV negative
- •Not pregnant or lactating
- •Inclusion Criteria (for PLWH (HIV-positive) cohort AA)
- •PLWH adults aged 18 to 45 years at consent
- •Participants on anti-retroviral (ARV) therapy with CD4 counts >350 and viral loads that are undetectable.
- •Not pregnant or lactating
排除标准
- •Known history or allergy to investigational vaccine components, other preventive vaccines, or any other allergies
- •Individuals with major congenital abnormalities
- •Known history of immune function disorders including immunodeficiency diseases (known HIV infection in healthy participant cohorts) or other immune function disorders (all cohorts).
- •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.
- •Behavioral or cognitive impairment, chronic substance abuse, or psychiatric disease or neurological disorders.
- •Individuals with a known bleeding disorder.
- •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 or within 4 weeks after any dose of the investigational product.
- •Individuals with active or previous Vibrio cholerae infection.
- •Individuals with receipt of a cholera vaccine in the past 5 years.
研究组 & 干预措施
Arm A4: Euvichol®-Plus
Euvichol®-Plus, HIV Negative Group, 18-45 years
干预措施: Active Comparator, Euvichol®-Plus (Biological)
Arm B2: Euvichol®-Plus
Euvichol®-Plus, HIV Negative Group, 6-17 years
干预措施: Active Comparator, Euvichol®-Plus (Biological)
Arm C2: Euvichol®-Plus
Euvichol®-Plus, HIV Negative Group, 1-5 years
干预措施: Active Comparator, Euvichol®-Plus (Biological)
Arm AA2: Euvichol®-Plus
Euvichol®-Plus, People living with HIV, 18-45 years
干预措施: Active Comparator, Euvichol®-Plus (Biological)
Arm A1: Biovac OCV-S
Biovac OCV-S (Lot 1), HIV Negative Group, 18-45 years
干预措施: Experimental: Biovac OCV-S (inactivated whole-cell monovalent (O1) oral cholera vaccine) (Biological)
Arm A2: Biovac OCV-S
Biovac OCV-S (Lot 2), HIV Negative Group, 18-45 years
干预措施: Experimental: Biovac OCV-S (inactivated whole-cell monovalent (O1) oral cholera vaccine) (Biological)
Arm A3: Biovac OCV-S
Biovac OCV-S (Lot 3), HIV Negative Group, 18-45 years
干预措施: Experimental: Biovac OCV-S (inactivated whole-cell monovalent (O1) oral cholera vaccine) (Biological)
Arm B1: Biovac OCV-S
Biovac OCV-S, HIV Negative Group, 6-17 years
干预措施: Experimental: Biovac OCV-S (inactivated whole-cell monovalent (O1) oral cholera vaccine) (Biological)
Arm C1: Biovac OCV-S
Biovac OCV-S, HIV Negative Group, 1-5 years
干预措施: Experimental: Biovac OCV-S (inactivated whole-cell monovalent (O1) oral cholera vaccine) (Biological)
Arm AA1: Biovac OCV-S
Biovac OCV-S, People living with HIV, 18-45 years
干预措施: Experimental: Biovac OCV-S (inactivated whole-cell monovalent (O1) oral cholera vaccine) (Biological)
结局指标
主要结局
Seroconversion of vibriocidal titers against Vibrio cholerae O1 Inaba and O1 Ogawa
时间窗: 2 weeks after second dose of either Biovac OCV-S (i.e., one lot of Biovac OCV-S) or Euvichol®-Plus
Proportion of participants showing seroconversion of vibriocidal titers against Vibrio cholerae O1 Inaba and O1 Ogawa (seroconversion is defined as at least 4-fold increase of vibriocidal titers compared to baseline) at 2 weeks after second dose of either Biovac OCV-S (i.e., one lot of Biovac OCV-S) or Euvichol®-Plus for all ages, in the HIV negative group.
Incidence of Treatment-Emergent Adverse Events in the HIV negative group
时间窗: Within 14 days after each vaccination
Safety of each investigational product dose at a specified duration in the HIV negative group: 1. Occurrence of any Serious Adverse Event (SAE)/ Adverse Event of Special Interest (AESI)/ Medically Attended Adverse Event (MAAE) from the first dose vaccination throughout the final study visit 2. Occurrence of immediate adverse events within 30 minutes after each dose vaccination 3. Occurrence of solicited adverse events within 7 days after each dose vaccination 4. Occurrence of unsolicited adverse events within 14 days after each dose vaccination
次要结局
- Geometric Mean Titer (GMT) of vibriocidal antibodies against Vibrio cholerae O1 Inaba and Ogawa for all ages(2 weeks after second dose of either Biovac OCV-S (i.e., one lot of Biovac OCV-S) or Euvichol®-Plus)
- Proportion of participants showing seroconversion against Vibrio cholerae O1 Inaba and Ogawa(2 weeks after second dose of either Biovac OCV-S (i.e., one lot of Biovac OCV-S) or Euvichol®-Plus)
- GMT of vibriocidal antibodies against Vibrio cholerae O1 Inaba and Ogawa in each age stratum(2 weeks after second dose of either Biovac OCV-S (i.e., one lot of Biovac OCV-S) or Euvichol®-Plus)
- GMT of vibriocidal antibodies against Vibrio cholerae O1 Inaba and Ogawa in adults(2 weeks after second dose of 3 lots of Biovac OCV-S)