Randomized, Controlled, Phase 1 Study to Assess Safety and Immunogenicity of Co-administered Hookworm Vaccine Candidates Na-GST-1 and Na-APR-1 Adjuvanted With Alhydrogel® and Gluco-pyranosylphospho-lipid A in Gabonese Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- Vaccine-related Adverse Events
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 with 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 Gabonese 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.
Study site: Centre de Recherches Médicales de Lambaréné Number of participants: 32 in 2 cohorts of 16
Doses of Na-GST-1 to be tested: 30 and 100 μg Doses of Na-APR-1 to be tested: 30 and 100 μg Dose of GLA-AF: 5 μg per antigen
Cohort 1: 30 μg of each of the two antigens (Na-GST-1/Alhydrogel® and Na-APR-1 (M74)/Alhydrogel®) or hepatitis B vaccine; Cohort 2: 100 μg of each of the two antigens (Na-GST- 1/Alhydrogel® and Na-APR-1 (M74) /Alhydrogel®) or hepatitis B vaccine.
Randomization: Cohort 1: 30 μg Na-GST-1 + 30 μg Na-APR-1 (M74) (n = 12) versus Hepatitis B Vaccine/placebo (n = 4) Cohort 2: 100 μg Na-GST-1 + 100 μg Na-APR-1 (M74) (n = 12) versus Hepatitis B Vaccine + placebo (n = 4)
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males or females between 18 and 50 years, inclusive, who are long-term residents of Gabon.
- •Good general health as determined by means of the screening procedure.
- •Assumed availability for the duration of the trial (12 months).
- •Willingness to participate in the study as evidenced by signing the informed consent document.
- •Negative for hookworm during screening, or if found to be infected with hookworm, has completed a course of three doses of albendazole.
排除标准
- •Pregnancy as determined by a positive urine hCG (if female).
- •Participant unwilling to use reliable contraception up until one month following the third immunization (if female and not surgically sterile, abstinent or at least 2 years post-menopausal).
- •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.
- •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).
- •Laboratory evidence of hematologic disease (absolute leukocyte count <3500/mm3; absolute leukocyte count >11.0 x 103/mm3; hemoglobin <10.000 g/dl [females] or <12.0 g/dl [males]; or, platelet count <140,000/mm3).
- •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 or for the duration of the study.
- •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 room/clinic visit or hospitalization within 6 months of the volunteer's planned first vaccination in the study.
- •Positive for HCV
- •Positive ELISA for HBsAg.
- •Positive for HIV infection
- •Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study or expect to use for the duration of the study.
- •Receipt of a live vaccine within past 4 weeks or a killed vaccine within past 2 weeks prior to entry into the study.
- •History of a surgical splenectomy.
- •Receipt of blood products within the 6 months prior to entry into the study.
- •Previous receipt of a primary series of any hepatitis B vaccine.
结局指标
主要结局
Vaccine-related Adverse Events
时间窗: Day 360
To estimate the frequency of vaccine-related adverse events, graded by severity, for each dose of co-administered Na-GST-1 and Na-APR-1 (M74). The frequency of immediate, systemic, and local injection site adverse events will be summarized. Adverse events will be assessed by study team members at 1 hour post-vaccination as well as 1, 3, 7, 14, and 28 days following each vaccination.
次要结局
- IgG response to Na-GST-1 and Na-APR-1 (M74)(Day 194)
- Duration of antibody response to Na-GST-1 and Na-APR-1 (M74)(Day 14, 28, 42, 56, 180, 194, 208, 270, 360)
- Exploratory studies of memory B-cell responses(Days 14, 28, 42, 56, 180, 194, 208, 270, 360)
研究者
Maria Elena Bottazzi PhD
Sponsor
Baylor College of Medicine