A Phase I Dose Escalation Study to Assess the Safety and Immunogenicity of the SF2a-TT15 Conjugate Vaccine Against S. Flexneri 2a in Healthy Adult Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Adverse Event
研究概览
简要总结
This is a first-in-human, single-center, single-blinded, observer-masked randomized, dose escalation (two doses), placebo-controlled study in healthy volunteers.
详细描述
Subjects will be assigned to one of two cohorts.
- Cohort 1 will receive the lower dose of 2 μg vaccine (with or without alum adjuvant) or matching placebo.
- Cohort 2 will receive the higher dose of 10 μg vaccine (with or without alum adjuvant) or matching placebo.
Eligible subjects will be randomized to receive the 2 μg dose or 10 µg without or with alum or matching placebo, at a ratio of 3:1, as three single IM injections. There will be an interval of 28(±3) days) between each treatment.
The study will be conducted in a stepwise approach in which a "Pioneer" Group of 2 subjects (one receiving the active vaccine and one receiving the matching placebo) will receive the first injection. These subjects will remain in-house for a 24-hours medical observation after the first injection (not required in the subsequent injections) Once it has been established that there are no safety concerns in the non-adjuvanted "Pioneer" Groups (and after no less than 48 hrs), the next "Pioneer" group (one subject receiving adjuvanted 2 μg vaccine and one receiving the matching alum placebo) will be injected.
If no safety concerns are raised in this group also, after no less than 48 hrs, the rest of the subjects may receive the first injection.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects in general good health in the opinion of the investigator as determined by medical history, vital signs and a physical examination.
- •Negative human leukocyte antigen (HLA) -B27 and no history of reactive arthritis
- •Negative HIV, Hepatitis B and Hepatitis C serology tests.
- •Blood levels of Shigella flexneri 2a LPS IgG antibodies ≤ percentile 80
- •No known history of alcohol abuse
排除标准
- •Subjects with a history of clinically significant gastrointestinal disorders or with any history of frequent diarrhea, nausea or emesis, regardless of etiology.
- •Individuals with immunosuppressive diseases or under immunosuppressive therapy
- •History of culture-proven S. flexneri.
- •Individuals who have household contact with/and /or intimate exposure to an individual with laboratory confirmed S. flexneri.
- •Having travelled in countries/areas highly endemic for S. flexneri within 3 months prior to enrolment.
- •Previous participation in any study in which a Shigella-vaccine candidate was administered.
- •Known contraindication, hypersensitivity and/or allergy to the investigational product or its excipients.
- •Known hypersensitivity and/or allergy to any drug or vaccine
- •Women who are pregnant or are breast-feeding, or are of childbearing age who have not used or do not plan to use acceptable birth control measures, for the duration of the study.
研究组 & 干预措施
vaccine dose 1+ adjuvant
SF2a-TT15 vaccine, 2 μg + alum
干预措施: SF2a-TT15 vaccine + adjuvant (Biological)
vaccine dose 2 + adjuvant
SF2a-TT15 vaccine, 10 μg + alum
干预措施: SF2a-TT15 vaccine + adjuvant (Biological)
Placebo
Tris buffer
干预措施: Placebo (Biological)
Placebo + adjuvant
Tris buffer + Alum
干预措施: Placebo + adjuvant (Biological)
vaccine dose 2
SF2a-TT15 vaccine, 10 μg
干预措施: SF2a-TT15 vaccine (Biological)
vaccine dose 1
SF2a-TT15 vaccine, 2 μg
干预措施: SF2a-TT15 vaccine (Biological)
结局指标
主要结局
Adverse Event
时间窗: 12 months
Safety: Occurrence, frequency, severity, and duration of local and systemic adverse events (AEs) including clinically significant laboratory abnormalities, after administration of the SF2a-TT15 vaccine.
次要结局
- Immunogenicity - humoral Immune response(12 months)