The Effect of Inhaled PUL-042 on Rhinovirus-induced Symptoms in Smokers With GOLD Stage 0 COPD

NCT03794557 | Completed Phase 2 DMC

• 1 other identifier: PUL-042-402
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

COPD

Outcome Measures

Primary Outcomes (1)

• 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.

  Daily Scores Day 0-42

Secondary Outcomes (11)

• Lower Respiratory Symptoms

  Daily Scores Days 0-42

• Lower Respiratory Symptoms

  Daily Scores Days 0-42

• Upper Respiratory Symptoms

  Daily Scores Days 0-42

• Upper Respiratory Symptoms

  Daily Scores Days 0-42

• Lung Function

  Days 0-42

Study Arms (2)

PUL-042

EXPERIMENTAL

PUL-042 Inhalation Solution

Drug: PUL-042 Inhalation Solution

Placebo

PLACEBO COMPARATOR

Sterile Water for injection

Drug: Sterile Water Injection

Interventions

Sterile Water Injection DRUG

Inhaled Sterile Water Injection

Placebo

PUL-042 Inhalation Solution DRUG

PUL-042 Inhalation Solution

PUL-042

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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;
• 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.

Sponsors & Collaborators

• Pulmotect, Inc.: lead
• Imperial College Healthcare NHS Trust: collaborator
• VirTus Respiratory Research Ltd: collaborator
• MWB Consulting Ltd: collaborator
• Data Magik Ltd: collaborator

Study Sites (1)

Imperial College Healthcare NHS Trust, St Mary Hospital

London, W2 1 NY, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 20889904 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Onn Min Kon, MD

  Imperial College Healthcare NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2018
• First Posted: January 7, 2019
• Study Start: January 21, 2019
• Primary Completion: December 16, 2020
• Study Completion: March 23, 2021
• Last Updated: June 1, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)