The Effect of Inhaled PUL-042 on Rhinovirus-induced Symptoms in Smokers With GOLD Stage 0 COPD
Condition: COPD
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a study examining the effect of inhaled PUL-042 on peak lower respiratory symptoms as
      measured by subject diary in early stage COPD subjects who are experimentally infected with
      rhinovirus.

      Subjects will receive 1 dose of PUL-042 followed by inoculation with HRV A16 virus 24 hours
      later. An additional dose of PUL-042 will be administered 48 hours post-inoculation. Subjects
      will be followed for 6 weeks post-inoculation
    

Detailed description: 
      This is a randomized, double-blind, placebo-controlled Phase 2 study examining the effects of
      inhaled PUL-042 on Lower Respiratory Symptom Score (LRSS) in GOLD stage 0 COPD patients.

      Smoking subjects (>10 pyh) with symptoms suggestive of early COPD (cough, sputum production
      but normal spirometry, meeting GOLD 0 criteria) will be screened. Following screening (days
      -21 to -11 prior to infection), eligible subjects will be enrolled and will undergo a
      baseline sampling visit on study day -8 and will complete questionnaires from study day -8 to
      -2 (7 days total) recording their baseline symptoms

      There will be two treatment arms in the study. The arms will be:

        -  Placebo administered on study day -1 and study day 2

        -  PUL-042 administered on study day -1 and PUL-042 administered on study day 2

      On day 0 subjects will be experimentally infected with HRV A16 (100 TCID50) via an atomizer
      to the upper airway. Subjects will subsequently be required to attend the clinic on study
      days 1-7, 9, 12, 15, 21 and 42 for follow up visits. Subjects will continue their diaries at
      home during the period when not attending clinic visits, namely days 8, 10, 11, 13, 14, 16-20
      and 22-41.

      Spirometry assessments will be conducted by clinic staff on clinic visit days. PEF, FEV1, FVC
      and FEV1/FVC ratio will be completed at the visit using the clinic study-supplied spirometry
      equipment.

      Sputum samples and serum will be analyzed for inflammatory markers. Serum samples will be
      obtained from subjects at screening and during clinic visits on study days -1, 0, 2, 3, 5, 7,
      9, 12, 15, 21 and 42. Sputum samples will be obtained at baseline (BL) and on study days -1,
      0, 2, 5, 7, 9, 12, 15, and 21.

      Nasal lavage samples will be collected during baseline (BL) and on study days -1, 0, 1-7, 9,
      12, 15, 21 and 42 for assessment of virus load and pro-inflammatory cytokines etc. in the
      upper airway.

      Subjects will be asked to complete the following questionnaires on days -8 to day 42 during
      the study:

        1. The lower respiratory symptom scores as measured by Mallia

        2. The upper respiratory symptoms measured by the Jackson score as measured by Mallia

        3. The COPD Assessment Test (CAT) score

        4. The EXACT-RS Lower Respiratory Symptom questionnaire

        5. The Wisconsin Upper Respiratory Symptom Survey-11 (WURSS-11)

        6. Subjects will record any medication use in a specific diary.
    

Intervention name(s): Sterile Water Injection; PUL-042 Inhalation Solution
Intervention type(s): Drug; Drug
Intervention description(s): Inhaled Sterile Water Injection; PUL-042 Inhalation Solution
Intervention MeSH terms: Pam2CSK4 acetate and ODN M362 combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment