A Phase 2a Age Descending Study to Investigate the Safety and Immunogenicity of the SF2a-TT15 Synthetic Carbohydrate-based Conjugate Vaccine Against Shigella Flexneri 2a in Adults, Children, and Infant Target Population in Endemic Countries.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 248
- 试验地点
- 1
- 主要终点
- Number, proportion,severity and relatedness of adverse events (AEs) to measure the safety and tolerability of SF2a-TT15 vaccine (2 μg OS and 10 μg OS) in each cohort.
研究概览
简要总结
A study among adults, children and infants in Kenya to determine if a new type of glycoconjugate vaccine incorporating a synthetic carbohydrate component is safe and induces immunity against Shigella.
详细描述
The purpose of this study is to examine the safety and immunogenicity of two doses of the parenteral synthetic carbohydrate-based conjugate vaccine against Shigella flexneri 2a (Shigella flexneri 2a-Tetanus Toxoid15 (SF2a-TT15)) adjuvanted or not with Alhydrogel in infants in an endemic country (Kenya), the target population for the vaccine, using an age-descending approach. In total, 232 participants will be enrolled in the study: 16 adults (18-50 years-old), 16 children (2-5 years-old) and 200 infants (9 months-old +/ 1 mo).
The vaccine will be tested in adults first, then in children and eventually in infants in Kenya (where Shigella infection is present), based on the safety/tolerability in each group before to moving to the other. Participants will be randomly assigned to receive the study vaccine or a placebo control (same solution but without the vaccine component). The participants will have to go through all the trial procedures including the 14 visits (3 injections and 11 follow-up) during a 16 months period.
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
Every team will be masked except the pharmacist and the pharmacy team on site and one dedicated personal within Sponsor team.
入排标准
- 年龄范围
- 8 Months 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For adults:
- •Healthy men and women between 18 and 50 (inclusive) years of age.
- •Subjects who provide written informed consent or thumb print in the presence of a witness to participate in the study
- •Women willing to use at least 1 reliable method of contraception during the study period, or are surgically sterilized, and agree to undergo repeated pregnancy tests (before each vaccination) and men willing to use an effective method of contraception (e.g. condom).
- •For children and infants:
- •Healthy boys and girls between 2 and 5 years of age for the children group (cohort 2)
- •Healthy boys and girls 9 mo-old (+/- 1 month) for the infant group (cohort 3)
- •Parents or legally acceptable representatives, as appropriate, who are willing and able to provide signed/thumb printed informed consent for children and infants.
- •Infant and children should have a normal nutritional Z score (-2 or greater) according to the mother and child health handbook of the republic of Kenya - Ministry of Health before entering the trial.
- •Signed/thumb written informed consent, in accordance with local practice, provided by adult volunteers (participants 18 years of age and older), parent(s) or legal representative(s) for children and infants participants as applicable, who, in the opinion of the Investigator, can and will comply with the requirements of the protocol.
- •Subjects in general good health in the opinion of the Investigator as determined by medical history, vital signs and a physical examination.
- •No clinically significant abnormalities in hematology, blood chemistry, or urinalysis laboratory tests at screening.
- •Negative HIV, Hepatitis B and Hepatitis C serology tests and malaria test.
排除标准
- •Subjects with a history of clinically significant gastrointestinal disorders (e.g. gastroesophageal reflux disease, peptic ulcer, celiac disease, inflammatory bowel disease).
- •Individuals with immunosuppressive diseases or under immunosuppressive therapy.
- •Previous participation in any study in which a Shigella-vaccine candidate was administered.
- •Suspected or known hypersensitivity (including allergy) to any of the vaccine components or to previous vaccine, or to medicinal products or medical equipment whose use is foreseen in this study.
- •Use of any prescription or over-the-counter (OTC) medications, within 14 days prior vaccination. Paracetamol or ibuprofen for symptomatic relief of pain is allowed until 48 hours prior to vaccination.
- •Women who are pregnant, breast-feeding, or are of childbearing age and are not on or do not plan to use acceptable contraceptives for the duration of the study.
- •Subjects with any significant acute medical situation (e.g. acute infection) within 48 hrs prior to study entry, in the opinion of the Principal Investigator.
- •Participation in another clinical trial with drugs within 3 months prior first study injection.
结局指标
主要结局
Number, proportion,severity and relatedness of adverse events (AEs) to measure the safety and tolerability of SF2a-TT15 vaccine (2 μg OS and 10 μg OS) in each cohort.
时间窗: 15 months
Solicited reactions, AEs, SAEs assessed post-vaccination using targeted physical examinations, vital signs, and clinical laboratory tests
Analyses of the serum anti-S. flexneri 2a lipopolysaccharide (LPS) IgG antibody response in the infant target population to assess the immunogenicity of the vaccine.
时间窗: 15 months
Proportion of responders (4-fold increases over baseline) in serum anti-S. flexneri 2a LPS IgG antibody response
次要结局
- The number and proportion of responders, the geometric mean titer (GMT), mean fold-rises (compared to baseline), and peak-post-vaccination of the serum bactericidal activity (SBA) antibody (functionality of SF2a-specific IgGs antibodies in infants).(15 months)
- Analyses of the serum anti-S. flexneri 2a LPS Immunoglobulins G (IgG) antibody response in the adult and children cohorts.(15 months)
- Comparison of the Measle-Rubella (MR) vaccine immune response in SF2a-TT15 vaccinees and placebo groups for the infant cohort.(15 months)