Influenza Antiviral DAS181-F03
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

Summary: 
      Influenza (flu) is a common respiratory infection and often causes severe illness. Few drugs
      are currently approved to treat influenza. This research will test the safety of an
      experimental anti-influenza drug called DAS181 that is given through an inhaler. The purpose
      of this study is to evaluate the safety of this new medication and how the body reacts to it.
      Any side effects will be measured by symptoms, physical examination or laboratory studies.
      About 27 healthy men and women age 18-45, who meet screening requirements, will participate.
      Three separate groups will be enrolled, with approximately 9 subjects in each group. Cohort
      1:20 mg DAS181 or placebo for 1 day (total dose of 20 mg). Cohort 2: 20 mg DAS181 or placebo
      for 10 consecutive days (total dose of 200 mg). Cohort 3: 30 mg DAS 181 or placebo for 1 day
      (total dose of 30 mg.) Procedures include blood samples, electrocardiograms (measures heart
      activity) and breathing tests.
    

Detailed description: 
      Influenza is typically caused by infection of two types of viruses, influenza virus A and
      influenza virus B. The host cell receptors for influenza A and B viruses are cell surface
      sialic acids (SA). The Actinomyces viscosus sialidase Catalytic Domain (AvCD) sialidase
      domain in DAS181 selectively cleaves sialic acids from the host cells, thereby rendering them
      inaccessible to the influenza viral particles that require sialic acids as receptors. By
      binding to the negatively charged glycosaminoglycans on the surface of airway epithelial
      cells, the cationic C-terminal Amphiregulin (AR) tag anchors DAS181 on the respiratory
      epithelium, thereby improving treatment potency and retention of the investigational drug on
      the airway surface. DAS181 is the first candidate in a new class of influenza therapeutics,
      viral receptor inactivator. The primary objective is to determine the safety and tolerability
      of DAS181 encapsulated dry powder compared to placebo when administered by oral inhalation
      using a dry powder inhaler (DPI) in healthy adults. The secondary objective of this study is
      to investigate the pharmacokinetic and immunologic profile of DAS181 encapsulated dry powder
      dose to dose and compared to placebo when administered by oral inhalation using a DPI in
      healthy adults. A total of 27 normal healthy male and female subjects (9 per cohort) 18 to 45
      years of age at the time of screening will be included in this study. This study will be a
      double-blind, randomized, placebo-controlled study of a three cohorts. Cohort 1:20 mg DAS181
      or placebo for 1 day (total dose of 20 mg). Cohort 2: 20 mg DAS181 or placebo for 10
      consecutive days (total dose of 200 mg). Cohort 3: 30 mg DAS 181 or placebo for 1 day (total
      dose of 30 mg.) The study will proceed to the next stage of multiple daily doses based on
      meeting study defined criteria. Within each dose cohort of nine, subjects will be randomly
      assigned to DAS181 or placebo at 2:1 ratios. Subjects will be admitted to the inpatient
      clinic on the day prior to first dose (Day -1). The subjects in single dose cohorts (Cohort 1
      and 3) will stay in the inpatient unit for dosing (Day 0) and one day after dosing (Day 1).
      Subjects in Cohort 1 will come back for follow-up visits on Study Days 2, 3, 7, 14, and 30 .
      Subjects in Cohort 3 will return on Days 2, 3, 4, 5, 8. 10, 16, and 30. The subjects in the
      10-day, multiple-dose cohort (Cohort 2) will stay in the inpatient clinic from Day -1 to 1
      and will be required to come back for follow-up visits on Days 2 - 7. They will be seen (and
      optionally readmitted) Days 8 - 10 and will be seen as outpatients Days 11, 13, 15, 17, 20,
      22, 24, and 27. All subjects will be asked to return for an additional blood draw to conduct
      an immunogenicity test at 90 days post final dosing. Subjects will be trained in proper
      inhalation techniques prior to dosing using a low range inspiratory flow measurement device.
    

Intervention name(s): Placebo; DAS181
Intervention type(s): Drug; Drug
Intervention description(s): Placebo: Cohort 1: 20mg DAS181 or placebo for 1 day (total dose of 20mg). Cohort 2: 20mg DAS181 or placebo for 10 consecutive days (total dose of 200mg). Cohort 3: 30mg DAS181 or placebo for 1 day (total dose of 30mg).; DAS181 F03: Cohort 1: 20mg DAS181 or placebo for 1 day (total dose of 20mg). Cohort 2: 20mg DAS181 or placebo for 10 consecutive days (total dose of 200mg). Cohort 3: 30mg DAS181 or placebo for 1 day (total dose of 30mg).
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: influenza, DAS181, antiviral