A Phase I/II Study of the Safety, Immunogenicity, and Efficacy of Sm-TSP-2/Alhydrogel® With or Without AP 10-701 for Intestinal Schistosomiasis in Healthy Ugandan Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 290
- 试验地点
- 1
- 主要终点
- Safety and Tolerability: frequency of local and systemic reactogenicity events
研究概览
简要总结
The study will recruit up to 290 healthy adult males and non-pregnant females into a two-part clinical trial of a vaccine to protect against schistosomiasis caused by infection with S. mansoni. Two formulations of the Sm-TSP-2 vaccine will be tested: one using Alhydrogel® only, and one using Alhydrogel® plus AP 10-701, each at 3 different doses of antigen: 10mcg, 30mcg, and 100mcg.
The first part of the study will be a Phase I dose-escalation safety and immunogenicity study followed by a Phase IIb trial in which a larger number of adults will be enrolled to assess the impact of the vaccine on infection with S. mansoni. The impact of the vaccine on infection with S. haematobium will also be assessed although this will be exploratory given that potential cross-protection against this species is only hypothetical at this point.
详细描述
The study will recruit up to 290 healthy adult males and non-pregnant females into a two-part clinical trial of a vaccine to protect against schistosomiasis caused by infection with S. mansoni. Two formulations of the Sm-TSP-2 vaccine will be tested: one using Alhydrogel® only, and one using Alhydrogel® plus AP 10-701, each at 3 different doses of antigen: 10mcg, 30mcg, and 100mcg.
The first part of the study will be a Phase I dose-escalation safety and immunogenicity study followed by a Phase IIb trial in which a larger number of adults will be enrolled to assess the impact of the vaccine on infection with S. mansoni. The impact of the vaccine on infection with S. haematobium will also be assessed although this will be exploratory given that potential cross-protection against this species is only hypothetical at this point.
Part A: double blind (within cohort), randomized, controlled, dose-escalation Phase 1b clinical trial in S. mansoni exposed adults living in the area of Kampala, Uganda. In each of 3 cohorts, subjects will be randomly assigned to 1 of 3 groups: Sm-TSP-2/Alhydrogel®, Sm-TSP-2/Alhydrogel®/AP 10-701, or the licensed Hepatitis B vaccine (up to 12 subjects per study vaccine group and 6 subjects in the Hepatitis B vaccine group). Subjects will receive three doses of the assigned vaccine delivered intramuscularly at approximately Days 0, 56, and 112.
Safety will be measured from the time of each study vaccination (Days 0, 56, 112 [Visits 2, 7, 12]) through 7 days after each study vaccination by the occurrence of solicited injection site and systemic reactogenicity events. Unsolicited non-serious adverse events (AEs) will be collected from the time of each study vaccination through approximately 28 days after each study vaccination. New-onset chronic medical conditions (including adverse events of special interest [AESI]) and serious adverse events (SAEs) will be collected from the time of the first study vaccination (Day 0 [Visit 2]) through approximately 9 months after the third study vaccination (Day 380 [Visit 19]). Clinical laboratory evaluations for safety will be performed on venous blood collected approximately 7 days after each study vaccination.
Immunogenicity testing will include IgG antibody responses to Sm-TSP-2 by a qualified indirect ELISA on serum obtained prior to each study vaccination (Days 0, 56, 112) and at time points after each vaccination.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Provide written informed consent prior to any study procedures.
- •Able to understand and comply with planned study procedures and be available for all study visits.
- •Male or non-pregnant female aged 18 to 45, inclusive at the time of enrollment.
- •Are in good health, as determined by vital signs (oral temperature, pulse, and blood pressure), medical history, and brief physical examination at screening.
- •Vital signs (oral temperature, pulse, and blood pressure) are all within normal protocol-defined ranges.
- •Laboratory tests (alanine aminotransferase [ALT], creatinine, white blood cell count (WBC), hemoglobin, and platelets) are all within protocol-defined reference ranges.
- •Urinalysis with no greater than trace protein and negative for glucose.
- •Female subjects of childbearing potential must agree to practice highly effective contraception for a minimum of 30 days prior to first vaccination and for 30 days after last vaccination.
- •Female subjects of childbearing potential must have a negative urine pregnancy test within 24 hours prior to study vaccination.
- •Able to correctly answer all questions on the informed consent comprehension questionnaire.
排除标准
- •Has the intention to become pregnant within 5 months after enrollment in this study.
- •Female subjects who are breastfeeding or plan to breastfeed at any given time from the first study vaccination until 30 days after their last study vaccination.
- •Has an acute illness, including a documented oral temperature of 38.0°C or greater, within 72 hours prior to vaccination.
- •Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes, or renal disease by history, physical examination, and/or laboratory studies.
- •Is immunosuppressed as a result of an underlying illness or treatment.
- •Using or intends to continue using oral or parenteral steroids, high-dose inhaled steroids (>800 μg/day of beclomethasone dipropionate or equivalent) or other immunosuppressive or cytotoxic drugs.
- •Positive test for HIV infection.
- •Volunteer has had a history of alcohol or illicit drug abuse during the past 23 months.
- •Received immunoglobulin or other blood products (with exception of Rho D immunoglobulin) within 90 days prior to study vaccination.
- •History of a severe allergic reaction or anaphylaxis to known components of the study vaccines.
- •Has an acute or chronic medical condition that, in the opinion of the investigator, would render participation in this study unsafe or would interfere with the evaluation of responses.
- •History of splenectomy.
- •Is participating or plans to participate in another clinical trial with an interventional agent during the duration of the study.
- •Received any licensed live vaccine within 30 days or any licensed inactivated vaccine within 14 days prior to the first study vaccination.
- •Planned receipt of any vaccine from the first study vaccination through 28 days after the last study vaccination.
- •Has any diagnosis, current or past, of schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations.
- •Has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
- •Anti-Sm-TSP-2 IgE antibody level above ELISA reactivity threshold.
- •Part A Only:
- •Positive hepatitis B surface antigen (HBsAg).
- •Positive confirmatory test for hepatitis C virus (HCV) infection.
- •Part B Only:
- •Negative for Schistosoma mansoni eggs, as assessed by the Kato Katz fecal thick smear during screening.
研究组 & 干预措施
Part A, Group A (Sm-TSP-2/Alhydrogel 10 mcg)
Sm-TSP-2/Alhydrogel Schistosomiasis Vaccine, delivered by IM injection on study days 0, 56, and 12; 10 mcg dose
干预措施: Sm-TSP-2/Alhydrogel® vaccine (Biological)
Part A, Group B (Sm-TSP-2/Alhydrogel 10 mcg + AP 10-701)
Sm-TSP-2/Alhydrogel Schistosomiasis Vaccine plus AP 10-701, delivered by IM injection on study days 0, 56, and 12; 10 mcg dose
干预措施: Sm-TSP-2/Alhydrogel® vaccine plus AP 10-701 (Biological)
Part A, Group C (Sm-TSP-2/Alhydrogel 30 mcg)
Sm-TSP-2/Alhydrogel Schistosomiasis Vaccine, delivered by IM injection on study days 0, 56, and 12; 30 mcg dose
干预措施: Sm-TSP-2/Alhydrogel® vaccine (Biological)
Part A, Group D (Sm-TSP-2/Alhydrogel 30 mcg + AP 10-701)
Sm-TSP-2/Alhydrogel Schistosomiasis Vaccine plus AP 10-701, delivered by IM injection on study days 0, 56, and 12; 30 mcg dose
干预措施: Sm-TSP-2/Alhydrogel® vaccine plus AP 10-701 (Biological)
Part A, Group E (Sm-TSP-2/Alhydrogel 100 mcg)
Sm-TSP-2/Alhydrogel Schistosomiasis Vaccine, delivered by IM injection on study days 0, 56, and 12; 100 mcg dose
干预措施: Sm-TSP-2/Alhydrogel® vaccine (Biological)
Part A, Group F (Sm-TSP-2/Alhydrogel 100 mcg + AP 10-701)
Sm-TSP-2/Alhydrogel Schistosomiasis Vaccine plus AP 10-701, delivered by IM injection on study days 0, 56, and 12; 100 mcg dose
干预措施: Sm-TSP-2/Alhydrogel® vaccine plus AP 10-701 (Biological)
Part A, Group G (HBV)
Hepatitis B Vaccine
干预措施: ENGERIX-B Hepatitis B Vaccine (Biological)
Part B, Group H (Sm-TSP-2/Alhydrogel +/- AP 10-701)
Sm-TSP-2/Alhydrogel Schistosomiasis Vaccine, with or without AP 10-701, dose and formulation determined in Part A
干预措施: Sm-TSP-2/Alhydrogel® vaccine (Biological)
Part B, Group I (HBV)
Hepatitis B Vaccine
干预措施: ENGERIX-B Hepatitis B Vaccine (Biological)
结局指标
主要结局
Safety and Tolerability: frequency of local and systemic reactogenicity events
时间窗: 7 days post-vaccination
Frequency of solicited injection site and systemic reactogenicity, graded by severity, on the day of each study vaccination through 7 days after each study vaccination.
Safety and Tolerability: frequency of unsolicited adverse events
时间窗: 28 days post-vaccination
Frequency of unsolicited adverse events, graded by severity, from the time of each study vaccination through approximately 1 month after each study vaccination.
Safety and Tolerability: frequency of vaccine-related Serious Adverse Events
时间窗: 23 months
Frequency of study vaccine-related Serious Adverse Events from the time of the first study vaccination through the final study visit.
Safety and Tolerability: frequency of clinical safety laboratory adverse events
时间窗: 7 days post-vaccination
Frequency of clinical safety laboratory adverse events measured 7 days after each vaccination
Safety and Tolerability: frequency of new-onset chronic medical conditions
时间窗: 23 months
Frequency of new-onset chronic medical conditions, including Adverse Events of Special Interest, through the final study visit
Efficacy: proportion of subjects with detectable S. mansoni eggs
时间窗: 12 and 23 months
Proportion of subjects with detectable S. mansoni eggs at 12 and 23 months in fecal samples, as determined by Kato Katz fecal thick smear.
Efficacy: mean S. mansoni eggs per gram of feces
时间窗: 12 and 23 months
Mean S. mansoni eggs per gram as determined by fecal microscopy (Kato Katz fecal thick smear) at 12 and 23 months.
Efficacy: Proportion of subjects with a positive CAA test
时间窗: 12 and 23 months
Proportion of subjects with a positive CAA test at 12 and 23 months.
次要结局
- Immunogenicity: peak anti-Sm-TSP-2 IgG level(Day 126)
- Immunogenicity: anti-Sm-TSP-2 IgG levels over time(Approximately 14 days after doses one and two and at Days 200, 290, 380 (Parts A and B) after final dose, and at Days 548, and 800 (Part B) after final dose.)
研究者
Maria Elena Bottazzi PhD
Co-Director
Baylor College of Medicine