A Phase I Double-Blind, Placebo-Controlled, Dose-Escalating Study to Evaluate the Safety and Tolerability of Topical Nasal Poly-ICLC
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 2
- 主要终点
- Frequency of AE greater than or equal to grade 2 by subjects who receive drug
研究概览
简要总结
This study will examine the safety of an experimental medication called Poly-ICLC, developed for preventing or reducing the severity of infections from influenza and other viruses acquired through the nose, mouth and lungs. The study is divided into two parts, in which Poly-ICLC is tested at different dose levels.
Healthy people between 18 and 70 years of age who have no chronic medical problems may be eligible for this study. Participants undergo the following procedures:
Part I
- Up to 7 days before Poly-ICLC administration: Medical history, physical examination and blood tests.
- Day 1: Nasal wash and Poly-ICLC administration. A small amount of salt water is placed into the front of the nose and then suctioned out. Poly-ICLC is then squirted into each nostril, one after the other, at a dose of 0.25, 0.5 or 1 mg. A small number of subjects are given a placebo (a solution with no active ingredient.) Subjects are observed in the clinic for 30 minutes after treatment.
- Day 2: Subjects receive a second nasal wash and repeat blood tests. They keep a diary card for 1 week, recording any drug side effects.
- Day 5: Subjects have repeat blood tests and a review of their diary card. The keep a diary card for another 3 weeks.
- Day 12: Subjects are contacted by phone to review their diary card.
- Day 28: Subjects are contacted by phone to review their diary card.
Part II
- Up to 7 days before Poly-ICLC administration: Medical history, physical examination and blood tests.
- Day 1: Nasal wash and Poly-ICLC administration. Same as above for Part I participants.
- Day 3: Subjects receive a second dose of medication and are observed again for 30 minutes.
- Day 4: Subjects receive a second nasal wash and repeat blood tests. They keep a diary card for 1 week, recording any drug side effects.
- Day 7: Subjects have repeat blood tests and a review of their diary card. The keep a diary card for another 3 weeks.
- Day 14: Subjects are contacted by phone to review their diary card.
- Day 28: Subjects are contacted by phone to review their diary card.
详细描述
Polyinosinic-Polycytidylic acid stabilized with polylysine and carboxymethylcellulose (Poly-ICLC), a stabilized double stranded RNA (dsRNA) therapeutic viral mimic activating innate and adaptive immunity, has been in extensive preclinical and investigational clinical therapeutic use as an intramuscular and intravenous compound, most recently in oncology applications. Only recently have the mechanisms of action been more fully elucidated, including induction of interferons, cytokines, and chemokines. Recognizing this, the infectious disease applications have been pursued in in vitro and animal models. Intranasal Poly-ICLC provides protection against mortality in animal models for multiple highly pathogenic viruses including influenza, severe acute respiratory distress syndrome (SARS), smallpox and Ebola. As its effects are not dependant on knowing the causative virus, an effective compound that could be protective against several unknown respiratory viruses has significant clinical appeal. While there is clinical safety data for intramuscular (IM) Poly-ICLC, no clinical studies of nasal application of Poly-ICLC have been done.
This study is a phase I safety and pharmacokinetic trial of nasally applied Poly-ICLC. Human volunteers will be administered increasing doses of nasal Poly-ICLC, with serial evaluation of safety, tolerability, as well as exploratory markers of immune activation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Frequency of AE greater than or equal to grade 2 by subjects who receive drug
次要结局
- Intranasal cytokines, nasal NO production, inflammatory cells in nasal wash