Phase 1 Study of the Safety and Immunogenicity of Na-APR-1 (M74)/Alhydrogel® Co-administered With Na-GST-1/Alhydrogel® in Brazilian Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Frequency of unsolicited adverse events, graded by severity, from the time of each study vaccination through approximately 1 month after each study vaccination.
研究概览
简要总结
Na-GST-1 and Na-APR-1 are proteins expressed during the adult stage of the Necator americanus hookworm life cycle that are thought to play a role in the parasite's degradation of host hemoglobin for use as an energy source. Vaccination wtih recombinant GST-1 or APR-1 has protected dogs and hamsters from infection in challenge studies. This study will evaluate the safety and immunogenicity of co-administering Na-GST-1 and Na-APR-1 to healthy Brazilian adults living in an area of endemic hookworm infection.
详细描述
Double blind, randomized, controlled, dose-escalation Phase 1 clinical trial in hookworm exposed adults living in the area of Americaninhas, Minas Gerais, Brazil. Subjects will receive three doses of the assigned vaccine delivered intramuscularly on approximately Days 0, 56, and 112.
Safety will be measured from the time of each study vaccination (Day 0) through 14 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 the first study vaccination through approximately 1 month after each study vaccination. New-onset chronic medical conditions and Serious Adverse Events (SAEs) will be collected from the time of the first study vaccination through approximately 9 months after the third study vaccination (final visit). Clinical laboratory evaluations for safety will be performed on venous blood collected approximately 14 days after each vaccination.
Immunogenicity testing will include IgG antibody responses to each vaccine antigen, by an indirect enzyme-linked immunosorbent assay (ELISA) and also by ImmunoCAP, on serum obtained prior to each study vaccination and at time points after each vaccination; antibody affinity by Surface Plasmon Resonance; functional activity of vaccine-induced antibodies via in vitro enzyme neutralization assays; and, antigen-specific memory B cell responses.
Recruitment and enrollment into the study will occur on an ongoing basis, with each group being recruited and vaccinated in sequence.
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
- Triple (Participant, 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
- •Males or non-pregnant females between 18 and 45 years, inclusive.
- •Good general health as determined by means of the screening procedure.
- •Available for the duration of individual subject study participation (16 months).
- •Willingness to participate in the study as evidenced by signing the informed consent document.
排除标准
- •Pregnancy as determined by a positive urine hCG (if female).
- •Subject unwilling to use reliable contraception (as described in Section 2.3.1) from 30 days prior to the first immunization and up until one month following the third immunization (if female and not surgically sterile, abstinent or at least 2 years post-menopausal, or determined otherwise by medical evaluation to be sterile).
- •Currently lactating and breast-feeding (if female).
- •Inability to correctly answer all questions on the informed consent comprehension questionnaire.
- •Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes, or renal disease by history, physical examination, and/or laboratory studies (a history of essential hypertension that is well controlled by medication will not be considered exclusionary.)
- •Has a diagnosis of schizophrenia, bipolar disease or other major psychiatric condition that would make compliance with study visits/procedures difficult (e.g., subject with psychoses or history of suicide attempt or gesture in the 3 years before study entry, ongoing risk for suicide).
- •Known or suspected immunodeficiency.
- •Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than 1.25-times the upper reference limit).
- •Laboratory evidence of renal disease (serum creatinine greater than 1.25-times the upper reference limit, or more than trace protein or blood on urine dipstick testing with the exception of greater than trace blood detected in females during menses).
- •Laboratory evidence of hematologic disease (absolute leukocyte count <3200/mm3; absolute leukocyte count >10.8 x 103/mm3; hemoglobin <11.4 g/dl [females] or <12.1 g/dl [males]; or, platelet count <130,000/mm3).
- •Serum glucose (random) greater than 1.2-times the upper reference limit.
- •Other condition that in the opinion of the investigator would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol.
- •Participation in another investigational vaccine or drug trial within 30 days of starting this study.
- •Previous receipt of the Na-GST-1/Alhydrogel® hookworm vaccine.
- •Volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
- •History of a severe allergic reaction or anaphylaxis.
- •Severe asthma as defined by the need for daily use of inhalers or emergency clinic visit or hospitalization within the last 6 months.
- •Positive test for hepatitis B surface antigen (HBsAg).
- •Positive confirmatory test for HIV infection.
- •Positive confirmatory test for hepatitis C virus (HCV) infection.
- •Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of the volunteer's expected first vaccination in this study or planned use up to one month following the last vaccination.
- •Receipt of a live vaccine within past 4 weeks or a killed vaccine within past 2 weeks prior to the volunteer's expected first vaccination in the study.
- •History of a surgical splenectomy.
- •Receipt of blood products within the past 6 months.
- •Anti-Na-GST-1 IgE antibody level above 0.35 kUA/L by the ImmunoCAP method.
- •Anti-Na-APR-1 IgE antibody level above ELISA reactivity threshold.
结局指标
主要结局
Frequency of unsolicited adverse events, graded by severity, from the time of each study vaccination through approximately 1 month after each study vaccination.
时间窗: 30 days post-vaccination
Frequency of solicited injection site and systemic reactogenicity, graded by severity, on the day of each study vaccination through 14 days after each study vaccination.
时间窗: 14 days post-vaccination
Frequency of study vaccine-related serious adverse events from the time of the first study vaccination through approximately 9 months after the last study vaccination.
时间窗: Day 380
Frequency of clinical safety laboratory adverse events.
时间窗: Day 380
Frequency of new-onset chronic medical conditions through approximately 9 months after the third study vaccination.
时间窗: Day 380
Frequency of Adverse Events of Special Interest through approximately 9 months after the third study vaccination.
时间窗: Day 380
次要结局
- The IgG level by an indirect enzyme-linked immunosorbent assay (ELISA) on approximately Day 126.(Day 126)
研究者
Maria Elena Bottazzi PhD
Sponsor
Baylor College of Medicine