GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage 0 Chronic Obstructive Pulmonary Disease (COPD) MedDRA version: 21.1 Level: PT Classification code 10009033 Term: Chronic obstructive pulmonary disease System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: PUL-042
Pharmaceutical Form: Concentrate for nebuliser solution
INN or Proposed INN: Pam2
Current Sponsor code: Pam2
Other
Sponsors
Pulmotect, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects will be eligible for entry into the study if they fulfil all of the following inclusion criteria: 1. Male or female subjects, aged 18-75 years inclusive, 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; 2. Current smokers with =10 pyh; 3. 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; 4. CAT score at screening =3 and less than or equal to 15; 5. Sero-negativity to HRV A16 neutralizing antibody; 6. 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. Acceptable methods of birth control in this study include: combined (oestrogen and progestogen containing) hormonal contraception associated with the inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, placement of an intrauterine device, placement of an intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner (provided that the partner is the sole sexual partner of a female trial participant [if they are a woman of child bearing potential] and that the vasectomised partner has received medical assessment of the surgical success), or true sexual abstinence (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject). Periodic abstinence (calendar, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. These contraceptive methods must be used during study participation. Additional pregnancy testing will be performed for female subjects who consent to take part in the study, from the Baseline Visit up to and including the final Follow-up Visit. If any pregnancy test indicates that an active study participant is pregnant, the patient will be withdrawn in accordance with Section 11.2 of the protocol and all necessary follow up completed (as per Section 12.4 of the protocol). A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. 7. Ability to understand and give informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1. Sero-positivity to HRV A16; 2. 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 before study day -1; 3. Subjects with evidence of an upper or lower respiratory infection within 6 weeks prior to study day -8; 4. A history or current evidence of bronchiectasis, cystic fibrosis, interstitial lung disease or other significant chronic lung disease; 5. A history within the last 5 years or current evidence of carcinoma of the bronchus; 6. A history within the last 5 years or current evidence of asthma; 7. A history of active tuberculosis or history of significant lung disease as a result of previous tuberculosis infection; 8. 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; 9. 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; 10. Use of cold preparations, anti-cholinergics, nasal lavage preparations or sprays, cough medications, or prescription or over-the-counter nasal decongestants within 30 days before study day -8; 11. Current (at screening and/or on any day from screening to study day -1) abuse of alcohol or illicit drugs, or history of alcohol or illicit drug abuse within the preceding 2 years; 12. A positive pregnancy test at baseline; 13. 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; 14. Inability to tolerate nebulization based on the Principal Investigator’s medical judgment or a =12% drop in FEV1 at study day -8, 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the effects of PUL-042 Inhalation Solution on peak lower respiratory symptom score (as measured by Mallia et al [see clinical protocol]) in GOLD stage 0 COPD subjects with an experimentally introduced rhinovirus infection with laboratory human rhinovirus strain HRV A16. All subjects will be negative for serum neutralizing antibody to HRV A16 at screening prior to viral inoculation. ;Primary end point(s): To determine the effects of PUL-042 Inhalation Solution on peak lower respiratory symptom score (as measured by Mallia et al [see clinical protocol]) in GOLD stage 0 COPD subjects with an experimentally-introduced rhinovirus infection with laboratory human rhinovirus strain HRV A16. ; Secondary Objective: The effect of PUL-042 on upper respiratory symptoms: • As measured by the Jackson score as measured by Mallia et al and the Wisconsin Upper Respiratory Symptom Survey-11 (WURSS-11). The effect of PUL-042 on lower respiratory symptoms: • As measured by Mallia et al, the Exacerbations of Chronic obstructive pulmonary disease Tool-Respiratory Symptoms (EXACT-RS) score and the COPD Assessment Test (CAT) score. The effect of PUL-042 on clinic-measured lung function tests: • PEF, FEV1, FVC and FEV1/FVC ratio. The effect of PUL-042 on the number of successfully infected patients, as determined by detectable virus load, or sero-conversion at day 42. The safety and tolerability of PUL-042 Inhalation Solution in ) in GOLD stage 0 COPD subjects with an experimentally introduced rhinovirus infection with laboratory human rhinovirus strain HRV A16. ; Timepoint(s) of evaluation of this end point: DAYS: -1 (predose, 15 min, 30 min, 1, 2, 4,6 and 8 hours post-dose); 0; 1; 2 (predose, 15 min, 30 min, 1, 2, 4,6 and 8 hours post-d | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The effect of PUL-042 on upper respiratory symptoms: • As measured by the Jackson score as measured by Mallia et al and the Wisconsin Upper Respiratory Symptom Survey-11 (WURSS-11), The effect of PUL-042 on lower respiratory symptoms: • As measured by Mallia et al, the EXAcerbations of Chronic obstructive pulmonary disease Tool-Respiratory Symptoms (EXACT-RS) score and the COPD Assessment Test (CAT) score. The effect of PUL-042 on clinic-measured lung function tests: • PEF, FEV1, FVC and FEV1/FVC ratio. The effect of PUL-042 on inflammatory mediators (nasal, sputum and serum) outcomes during the ~ 6 weeks post dosing. The effect of PUL-042 on the number of successfully infected patients, as determined by detectable virus load, or sero-conversion at day 42. The safety and tolerability of PUL-042 Inhalation Solution in ) in GOLD stage 0 COPD subjects with an experimentally introduced rhinovirus infection with laboratory human rhinovirus strain HRV A16. ; Timepoint(s) of evaluation of this end point: DAYS: -1 (predose, 15 min, 30 min, 1, 2, 4,6 and 8 hours post-dose); 0; 1; 2 (predose, 15 min, 30 min, 1, 2, 4,6 and 8 hours post-dose); 3-7 inclusive; 9, 12, 15 21 +/- 1 day; 42 +/-2 days. | — |
Countries
United Kingdom
Contacts
Public ContactBrenton Scott, PhD
Pulmotect, Inc.
Outcome results
None listed