Entolimod, an Adjuvant for Vaccine Augmentation
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Adverse events associated with entolimod augmentation.
研究概览
简要总结
The primary objective of this pilot study to evaluate the safety of low dose Entolimod in normal, healthy, non-patient normals. This clinical trial in 40 normal humans compares a single dose of 4 ug Td (2 ug of TT and 2 ug of diphtheria toxoid + 3000 ug of alum with or without entolimod. Subjects will be randomized to: Td alone (n=15) and Td+ entolimod (n=25). The investigators expect that Td + entolimod will double the anti-TT and anti-diphtheria AB levels over Td alone.
详细描述
This is a single-blind (participants are blinded), pilot study with no therapeutic or diagnostic intent and limited drug exposure. The study will be conducted at Baylor College of Medicine in normal, healthy, and non-drug using male volunteers who have not received the Td vaccination in the past 5 years.
The purpose of this study is to evaluate the safety and surrogate efficacy of low dose entolimod in normal, healthy, non-patient subjects by comparing anti-tetanus (TT) antibody levels between patients getting entolimod vs no entolimod combined with tetanus-diphtheria (Td) vaccine. Subjects will be randomly assigned to one of two arms in a 3:5 ratio (for every 8 subjects, 3 will be randomly assigned to the control group and 5 to the treatment group) to receive a single dose of:
Arm 1: Td (4 ug) (n=15), Arm 2: Td (4 ug) + Entolimod (1 ug) (n=25)
We propose to give the normal dose of Td given routinely to humans (i.e. TT at 2μg and diphtheria toxoid at 2 ug) for a total protein dose of 4 ug. The proposed dose of entolimod at 1 ug is 30-40 times lesser than that previously given safely to humans. We expect that Td + entolimod will double the anti-tetanus toxoid antibody (anti-TT AB) and anti-diphtheria AB levels over Td alone. We predict that this low dosing of entolimod (1μg) produces no difference in adverse effects from giving Td vaccine alone and that any adverse events will be no different than what is typical as reported in the Physicians' Desk Reference for Td vaccine in humans.
For purposes of this trial, study population age cut-off will be 40 years of age. The reason for this cut-off is that the body produces higher antibody levels in response to vaccines in younger age groups compared to older groups. Further, this study is restricted to males only as a safety measure so that women of child-bearing age are not exposed to entolimod, which has not been given to women of childbearing potential.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy, non-patient normal males between 18 and 40 years of age
- •No baseline anti-TT AB (tetanus toxoid antibody) levels greater than 5 µg/ml
- •Able to read/write/understand English and provide signed written informed consent prior to any study specific procedures.
排除标准
- •Inability to read/write English
- •Inability to provide written informed consent.
- •Any major cardiovascular, renal, endocrine, immunological (including positive test result for human immunodeficiency virus types 1 or 2 antibodies) or hepatic disorder (including positive test result for hepatitis B, hepatitis C virus antibodies, or liver function tests (LFT's)(SGOT, SGPT) that are 20% greater than normal levels or history of severe alcohol use disorder (defined as a score of 5 of greater on the MINI, based on DSM criteria).
- •Medical contraindication to treatment with vaccine as indicated by a history of autoimmune disease, immune deficiency, or hypersensitivity to other vaccines. Specific disorders include a prior Arthus-type hypersensitivity reaction to tetanus vaccine or any of its components, prior Guillain-Barre Syndrome, Ongoing active infection of any kind with clinical signs of febrile illness (temperature >99.5ºF).
- •Use of psychoactive or hepatotoxic medications or medications that might interact with the tetanus toxoid based vaccine including steroids within 30 days of screening, immunosuppressive or immunostimulant therapy.
- •Received other vaccines, including flu vaccine, within 30 days prior to screening or Tetanus vaccine within 5 years of this study (Advisory Committee on Immunization Practices (ACIP) guidelines.
- •Blood or blood products given in the 3 months prior to vaccination.
- •Participation in another investigational pharmaceutical trial within 30 days prior to screening.
- •Greater than Grade 1 abnormality in baseline safety labs (e.g, CBC and CMP), as defined using the FDA Guidance Document entitled "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials"
- •Greater than Grade 1 abnormality in baseline vital signs
- •Women, as a standard safety measure, will be excluded from the study due to childbearing potential and to minimize the effects of differences in hormonal levels during the menstrual cycle and of sex differences in antibody titer responses to vaccines. Furthermore, our sample size is too small to control for these effects in women.
- •Other concerns that in the PI's judgment will be a potential safety issue for the subject including cognitive impairment that precludes the ability to provide informed consent, and individuals with behavioral issues evidenced during screening or through the course of the trial that are disruptive and/or pose a safety concern to self or other subjects.
研究组 & 干预措施
Td vaccine with entolimod
Td vaccine (4 ug) + Entolimod (1 ug) (n=25)
干预措施: Entolimod (Drug)
Td vaccine with entolimod
Td vaccine (4 ug) + Entolimod (1 ug) (n=25)
干预措施: Td Vaccine (Biological)
Td vaccine only
Td vaccine (4 ug) (n=15)
干预措施: Td Vaccine (Biological)
结局指标
主要结局
Adverse events associated with entolimod augmentation.
时间窗: 6 weeks
The proposed dose of entolimod used in our study is 30-40 times lesser than that previously given safely to humans. Although our pre-clinical data suggest that these very low levels of entolimod efficiently enhances the antibody levels to TT vaccine in rodents, the safety and success rate at these low doses of entolimod to enhance anti-TT AB in humans requires examination.
次要结局
- Antibody titer comparison with entolimod augmentation of Td vaccine(6 weeks)
研究者
Thomas R. Kosten, MD
Waggoner Chair and Professor of Psychiatry, Neuroscience, Pharmacology, Immunology & Pathology Director, Dan Duncan Institute for Clinical and Translational Research
Baylor College of Medicine