The Effect of Inhaled PUL-042 on Rhinovirus-induced Symptoms in Smokers With GOLD Stage 0 COPD
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|ClinicalTrials.gov Identifier: NCT03794557|
Recruitment Status : Completed
First Posted : January 7, 2019
Last Update Posted : June 1, 2021
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
|Condition or disease||Intervention/treatment||Phase|
|COPD||Drug: Sterile Water Injection Drug: PUL-042 Inhalation Solution||Phase 2|
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:
- The lower respiratory symptom scores as measured by Mallia
- The upper respiratory symptoms measured by the Jackson score as measured by Mallia
- The COPD Assessment Test (CAT) score
- The EXACT-RS Lower Respiratory Symptom questionnaire
- The Wisconsin Upper Respiratory Symptom Survey-11 (WURSS-11)
- Subjects will record any medication use in a specific diary.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||A Phase 2, Single-Center, Double-Blind, Placebo-Controlled, Study of PUL-042 Inhalation Solution in Rhinovirus-induced Symptoms in Current Smokers With Gold Stage 0 Chronic Obstructive Pulmonary Disease (COPD)|
|Actual Study Start Date :||January 21, 2019|
|Actual Primary Completion Date :||December 16, 2020|
|Actual Study Completion Date :||March 23, 2021|
PUL-042 Inhalation Solution
Drug: PUL-042 Inhalation Solution
PUL-042 Inhalation Solution
Placebo Comparator: Placebo
Sterile Water for injection
Drug: Sterile Water Injection
Inhaled Sterile Water Injection
- Lower Respiratory Symptom Score as measured by Mallia et al (Am J Respir Crit Care Med. 2011) [ Time Frame: Daily Scores Day 0-42 ]The peak daily lower respiratory symptom score as measured by Mallia recorded in the 6 weeks post-infection period. This is a measure of a number of lower respiratory symptoms in a 24 hour period that include: shortness of breath (scale 0-4; 0 = not breathless, 4 = breathless at rest) wheeze (0-4; 0 = no wheeze, 4 = wheeze at rest), cough (0-3; 0 = no cough, 3 = severe cough), sputum quantity (0-3; 0 = none, 3 = large volume , more than 100 ml) sputum quality (0-3; 0 = none, 3 = purulent, green in colour). The total lower respiratory symptom score is the sum of all the above measurements (minimum 0, maximum 17) recorded on each day. These values will be recorded via a study diary over a six week period (day 0-42). Peak value is the highest daily total value over the 6 week post-infection period.
- Lower Respiratory Symptoms [ Time Frame: Daily Scores Days 0-42 ]The EXAcerbations of Chronic obstructive disease Tool-Respiratory Symptoms (EXACT-RS)
- Lower Respiratory Symptoms [ Time Frame: Daily Scores Days 0-42 ]COPD Assessment Test (CAT)
- Upper Respiratory Symptoms [ Time Frame: Daily Scores Days 0-42 ]Jackson Score as measured by Mallia et al (Am J Respir Crit Care Med. 2011). A modified Jackson score will be utilized which assesses the following eight upper respiratory symptoms daily: nasal congestion, runny nose, sneezing, cough, sore throat, general malaise, headache, chilliness (each scored 0-3 where 0 = none, 3 = severe). Minimum daily score= 0, maximum daily score= 24.
- Upper Respiratory Symptoms [ Time Frame: Daily Scores Days 0-42 ]Wisconsin Upper Respiratory Symptom Survey-11 (WURSS-11)
- Lung Function [ Time Frame: Days 0-42 ]Peak Expiratory Flow (PEF) L/min
- Lung Function [ Time Frame: Days 0-42 ]Forced Expiratory Volume in 1 Second (FEV1) L/second
- Lung Function [ Time Frame: Days 0-42 ]Forced Vital Capacity (FVC) L
- Lung Function [ Time Frame: Days 0-42 ]FEV1/FVC ratio
- Inflammatory Mediator [ Time Frame: Days 0-42 ]CXCL 10/IP-10 measured by ELISA in nasal secretions, sputum and serum. Results reported in pg/mL
- Inflammatory Mediator [ Time Frame: Days 0-42 ]IL-6 measured by ELISA in nasal secretions, sputum and serum. Results reported in pg/mL
- Number of successfully infected patients [ Time Frame: Days 0-42 ]Detectable virus load; seroconversion
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03794557
|Imperial College Healthcare NHS Trust, St Mary Hospital|
|London, United Kingdom, W2 1 NY|
|Principal Investigator:||Onn Min Kon, MD||Imperial College Healthcare NHS Trust|