Phase 1 Study of the Safety and Immunogenicity of Na-APR-1 (M74)/Alhydrogel® in Healthy Adults

Baylor College of Medicine2 个研究点分布在 1 个国家目标入组 40 人开始时间: 2013年9月最近更新: 2019年7月31日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Baylor College of Medicine
入组人数: 40
试验地点: 2
主要终点: Vaccine-related Adverse Events

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Hookworms digest hemoglobin from erythrocytes for use as an energy source via a proteolytic cascade that begins with the aspartic protease, APR-1. Vaccination with recombinant APR-1 has protected animals from infection in challenge studies. This study will evaluate the safety and immunogenicity of two formulations of Na-APR-1 (M74) in healthy adult volunteers when co-administered with different concentrations of the immunostimulant GLA-AF.

详细描述

Open-label, dose-escalation phase 1 clinical trial in healthy, hookworm-naïve adults:

Study site: George Washington Medical Faculty Associates, Washington, DC
Number of participants: 40 in 2 cohorts of 20.

In Cohort 1 five (5) volunteers will receive 30 µg Na-APR-1 (M74) /Alhydrogel®, five (5) will receive 30 µg Na-APR-1 (M74)/Alhydrogel® plus 2.5 µg GLA-AF, and ten (10) will receive 30 µg Na-APR-1 (M74) /Alhydrogel® plus 5 µg GLA-AF. In Cohort 2 five (5) volunteers will receive 100 µg Na-APR-1 (M74)/Alhydrogel®, five (5) will receive 100 µg Na-APR-1 (M74) /Alhydrogel® plus 2.5 µg GLA-AF, and ten (10) will receive 100 µg Na-APR-1 (M74)/Alhydrogel® plus 5 µg GLA-AF.

The cohorts will be enrolled in a staggered fashion with safety data assessed prior to the Na-APR-1 dose escalation from 30 to 100 µg. In addition, within each cohort, vaccinations will be staggered such that formulations containing 0, 2.5, and 5 µg GLA-AF will be tested sequentially: for example, those receiving Na-APR-1 (M74)/Alhydrogel® in combination with 2.5 µg GLA-AF will be vaccinated no sooner than 3 days after the last volunteer is vaccinated with the formulation containing no GLA-AF, whereas those vaccinated with Na-APR-1 (M74)/Alhydrogel® plus 5 µg GLA-AF will be vaccinated no sooner than 7 days after the last one receives the 2.5 µg GLA-AF formulation.

Immunization schedule: Study days 0, 56 and 112.
Route: IM in the deltoid muscle.
Doses of Na-APR-1 (M74) to be tested: 30 and 100 µg.
Doses of Alhydrogel®: 240 and 800 µg for the 30 and 100 µg doses of Na-APR-1 (M74), respectively.
Doses of GLA-AF to be tested: 2.5 µg and 5 µg.
Study duration: 44 weeks (10 months) per study participant; total duration of the study estimated at approximately 13 months.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Prevention
盲法: None

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.
•Good general health as determined by means of the screening procedure.
•Available for the duration of the trial (44 weeks).
•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 human choriogonadotropin (hCG) (if female).
•Participant unwilling to use reliable contraception methods 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).
•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 (hemoglobin <11.5 g/dl [females] or <12.5 g/dl [males]; absolute leukocyte count <3600/mm3 or >10.7 x 103/mm3; absolute neutrophil count [ANC] <1700/ mm3; absolute lymphocyte count <700/mm3; or platelet count <140,000/mm3).
•Laboratory evidence of a coagulopathy (PTT or PT INR greater than 1.1-times the upper reference limit).
•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.
•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 6 months of the volunteer's expected first vaccination in the study.
•Positive ELISA 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.
•Receipt of a live vaccine within 4 weeks or a killed vaccine within 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.
•History of previous infection with hookworm or residence for more than 6 months in a hookworm-endemic area.