COPDPhase 2NCT03794557
The Effect of Inhaled PUL-042 on Rhinovirus-induced Symptoms in Smokers With GOLD Stage 0 COPD
A Phase 2 study testing Sterile Water Injection and PUL-042 Inhalation Solution in people with COPD, run by Pulmotect, Inc. at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- COPD
- What is being tested?
- Sterile Water Injection and PUL-042 Inhalation Solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 21 Jan 2019to 23 Mar 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female subjects, with symptoms (cough, sputum production) suggestive of GOLD stage 0 COPD for at least one year prior to the screening visit in accordance with the GOLD 2014 guidelines;
- Current smokers with >10 pyh;
- Subject has risk of COPD defined by GOLD Staging Criteria level 0 where the subjects' post-bronchodilator FEV1/FVC ratio >0.70 and FEV1 is >80% normal predicted;
- CAT score at screening >3 and < 15;
- Sero-negativity to HRV A16 neutralizing antibody;
- Patients together with their partners of reproduction potential (males and females) must practice an acceptable method of birth control with a failure rate of a Pearl index of less than 1% per year, to be used consistently and correctly throughout the course of the study.
- Ability to understand and give informed consent.
Who cannot join
- Sero-positivity to HRV A16
- Use of systemic or nasal topical steroids, inhaled corticosteroids (ICS), systemic immunosuppressants, antibiotics, LABA, and LAMA and oral theophylline and/or roflumilast within 30 days;
- Subjects with evidence of an upper or lower respiratory infection within 6 weeks;
- A history or current evidence of bronchiectasis, cystic fibrosis, interstitial lung disease or other significant chronic lung disease;
- A history within the last 5 years or current evidence of carcinoma of the bronchus;
- A history within the last 5 years or current evidence of asthma;
Show all 14Show fewer
- A history of active tuberculosis or history of significant lung disease as a result of previous tuberculosis infection;
- A medical history or current clinical evidence of significant hematological, gastrointestinal, renal, hepatic, cerebrovascular, immunologic, psychiatric or cardiovascular disease or event (including uncontrolled hypertension as determined by the Investigator), or any clinical condition that may, in the opinion of the Investigator or Medical Monitor, impact on the subject's ability to participate in the study;
- Clinical laboratory values at screening for neutrophils, hemoglobin and hematocrit which reflect grade 2 or higher reductions from normal range, or ALT results which reflect grade 2 or higher elevations per the 'CTCAE' guidelines. Subjects with other clinical laboratory abnormalities outside normal reference ranges will be considered for inclusion, if in the opinion of the Principal Investigator or Medical Monitor the abnormalities are not clinically significant, or will not jeopardize the safety of the subject or the validity of the study;
- Use of cold preparations, anti-cholinergics, nasal lavage preparations or sprays, cough medications, or prescription or over-the-counter nasal decongestants within 30 days;
- Current abuse of alcohol or illicit drugs, or history of alcohol or illicit drug abuse within the preceding 2 years;
- A positive pregnancy test at screen;
- Received an investigational drug or vaccine within 30 days or 5 half-lives (whichever is longer), or use of an investigational medical device within 30 days prior to the screening visit or in the interval between screening and study day -1;
- Inability to tolerate nebulization based on the Principal Investigator's medical judgment or a ≥12% drop in FEV1, at either 15 or 30 minutes after the completion of administration of a dose of nebulization test solution (SWFI) of the same volume and under the same nebulization conditions that is planned to be used for study drug administration, compared to the FEV1 obtained immediately prior to administration of the nebulization test solution.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Imperial College Healthcare NHS Trust, St Mary Hospital
London, W2 1 NY
About this study
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)
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
Read the 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:
- 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.
- Conditions
- COPD
- Being tested
- Sterile Water Injection, PUL-042 Inhalation Solution
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sterile Water InjectionDrug
Inhaled Sterile Water Injection
PUL-042 Inhalation SolutionDrug
PUL-042 Inhalation Solution
| Study group | Role | What they receive |
|---|---|---|
| PUL-042 | Experimental | PUL-042 Inhalation Solution Receives: Drug: PUL-042 Inhalation Solution |
| Placebo | Placebo comparator | Sterile Water for injection Receives: Drug: Sterile Water Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lower Respiratory Symptom Score as measured by Mallia et al (Am J Respir Crit Care Med. 2011)
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.
Measured: Daily Scores Day 0-42
Secondary outcomes (11)
Lower Respiratory Symptoms
The EXAcerbations of Chronic obstructive disease Tool-Respiratory Symptoms (EXACT-RS)
Measured: Daily Scores Days 0-42
Lower Respiratory Symptoms
COPD Assessment Test (CAT)
Measured: Daily Scores Days 0-42
Upper Respiratory Symptoms
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.
Measured: Daily Scores Days 0-42
Upper Respiratory Symptoms
Wisconsin Upper Respiratory Symptom Survey-11 (WURSS-11)
Measured: Daily Scores Days 0-42
Lung Function
Peak Expiratory Flow (PEF) L/min
Measured: Days 0-42
Lung Function
Forced Expiratory Volume in 1 Second (FEV1) L/second
Measured: Days 0-42
Lung Function
Forced Vital Capacity (FVC) L
Measured: Days 0-42
Lung Function
FEV1/FVC ratio
Measured: Days 0-42
Inflammatory Mediator
CXCL 10/IP-10 measured by ELISA in nasal secretions, sputum and serum. Results reported in pg/mL
Measured: Days 0-42
Inflammatory Mediator
IL-6 measured by ELISA in nasal secretions, sputum and serum. Results reported in pg/mL
Measured: Days 0-42
Number of successfully infected patients
Detectable virus load; seroconversion
Measured: Days 0-42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2019
- Study start21 Jan 2019
- Primary completion16 Dec 2020
- Study completion23 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COPDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pulmotect, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Imperial College Healthcare NHS Trust, VirTus Respiratory Research Ltd, MWB Consulting Ltd, Data Magik Ltd
- Responsible party
- Sponsor
- Investigators
- Onn Min Kon, MD, Principal investigator, Imperial College Healthcare NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03794557
- Sponsor's protocol ID
- PUL-042-402
- Status last verified
- May 2021
- First submitted
- 24 Dec 2018
- Last updated
- 1 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mallia P, Message SD, Gielen V, Contoli M, Gray K, Kebadze T, Aniscenko J, Laza-Stanca V, Edwards MR, Slater L, Papi A, Stanciu LA, Kon OM, Johnson M, Johnston SL. Experimental rhinovirus infection as a human model of chronic obstructive pulmonary disease exacerbation. Am J Respir Crit Care Med. 2011 Mar 15;183(6):734-42. doi: 10.1164/rccm.201006-0833OC. Epub 2010 Oct 1.
PubMed 20889904
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03794557
- Acronym / sponsor ID
- PUL-042-402
- Conditions
- COPD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Pulmotect, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Imperial College Healthcare NHS Trust, VirTus Respiratory Research Ltd, MWB Consulting Ltd, Data Magik Ltd
- Study start
- 21 Jan 2019 (actual)
- Primary completion
- 16 Dec 2020 (actual)
- Study completion
- 23 Mar 2021 (actual)
- First posted
- 7 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PUL-042 | Experimental | Drug: PUL-042 Inhalation SolutionPUL-042 Inhalation Solution |
| Placebo | Placebo comparator | Drug: Sterile Water InjectionSterile Water for injection |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female subjects, with symptoms (cough, sputum production) suggestive of GOLD stage 0 COPD for at least one year prior to the screening visit in accordance with the GOLD 2014 guidelines;
- Current smokers with >10 pyh;
- Subject has risk of COPD defined by GOLD Staging Criteria level 0 where the subjects' post-bronchodilator FEV1/FVC ratio >0.70 and FEV1 is >80% normal predicted;
- CAT score at screening >3 and < 15;
- Sero-negativity to HRV A16 neutralizing antibody;
Key exclusion criteria (14 listed)
- Sero-positivity to HRV A16
- Use of systemic or nasal topical steroids, inhaled corticosteroids (ICS), systemic immunosuppressants, antibiotics, LABA, and LAMA and oral theophylline and/or roflumilast within 30 days;
- Subjects with evidence of an upper or lower respiratory infection within 6 weeks;
- A history or current evidence of bronchiectasis, cystic fibrosis, interstitial lung disease or other significant chronic lung disease;
- A history within the last 5 years or current evidence of carcinoma of the bronchus;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sterile Water InjectionInhaled Sterile Water Injection | Drug | Placebo |
| PUL-042 Inhalation SolutionPUL-042 Inhalation Solution | Drug | PUL-042 |
Primary outcome
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.
11 secondary outcomes
Lower Respiratory Symptoms
Time frame: Daily Scores Days 0-42
Lower Respiratory Symptoms
Time frame: Daily Scores Days 0-42
Upper Respiratory Symptoms
Time frame: Daily Scores Days 0-42
Upper Respiratory Symptoms
Time frame: Daily Scores Days 0-42
Lung Function
Time frame: Days 0-42
Lung Function
Time frame: Days 0-42
Lung Function
Time frame: Days 0-42
Lung Function
Time frame: Days 0-42
Inflammatory Mediator
Time frame: Days 0-42
Inflammatory Mediator
Time frame: Days 0-42
Number of successfully infected patients
Time frame: Days 0-42
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2021.
- Background: PubMed 20889904Mallia P, Message SD, Gielen V, Contoli M, Gray K, Kebadze T, Aniscenko J, Laza-Stanca V, Edwards MR, Slater L, Papi A, Stanciu LA, Kon OM, Johnson M, Johnston SL. Experimental rhinovirus infection as a human model of chronic obstructive pulmonary disease exacerbation. Am J Respir Crit Care Med. 2011 Mar 15;183(6):734-42. doi: 10.1164/rccm.201006-0833OC. Epub 2010 Oct 1.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Onn Min Kon, MD principal investigator
Imperial College Healthcare NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sterile Water Injection and PUL-042 Inhalation Solution in people with COPD, run by Pulmotect, Inc. at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lower Respiratory Symptom Score as measured by Mallia et al (Am J Respir Crit Care Med. 2011) (time frame: Daily Scores Day 0-42). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03794557, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2021.