Poly-ICLC to Prevent Respiratory Viral Infections A Safety Study
Condition: Influenza; Severe Acute Respiratory Distress Syndrome; Smallpox; Ebola; Unknown Respiratory Viruses
MeSH terms: Smallpox; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Poly-ICLC
Intervention type(s): Drug
Intervention MeSH terms: Poly ICLC
Allocation: Randomized
Intervention model: Single Group Assignment
Primary purpose: Treatment
Keywords: Antiviral; Influenza; Interferon; Prophylaxis; SARS; Healthy Volunteer; HV