Asthma, Chronic Obstructive Pulmonary Disease
Conditions
Keywords
asthma, chronic obstructive pulmonary disease, COPD, adhesion molecule, P-selectin glycoprotein ligand 1, P-selectin
Brief summary
This study has two parts. The main purpose of Part 1 of this study will be to examine how safe and effective two doses of SelK2 is on participants with mild asthma. Lung function and inflammatory cell numbers will be measured in response to the administration of an allergen (a compound to which the participant is allergic) into the lungs in the presence or absence of SelK2. Part 2 of this study will examine how safe and effective one dose of SelK2 is on participants with chronic obstructive pulmonary disease (COPD). Lung function and inflammatory cell numbers will be measured in COPD patients in the presence or absence of SelK2. SelK2 may block the movement of key inflammatory cells into the lungs and consequently improve lung function in these two patient populations.
Interventions
DRUGSelK2 (Part 1)
I.V., multiple-dose (Day 1 and Day 22)
DRUGPlacebo (Part 1)
I.V., multiple-dose (Day 1 and Day 22)
DRUGSelK2 (Part 2)
I.V., single-dose (Day 1)
DRUGPlacebo (Part 2)
I.V., single-dose (Day 1)
Sponsors
Tetherex Pharmaceuticals Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Part 1 of the study will enroll patients in two arms in a 1:1 ratio to receive either SelK2 or placebo. Part 2 of the study will enroll patients in two arms in a 2:1 ratio to receive either SelK2 or placebo, respectively.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Part 1: Key Inclusion Criteria * Males or females, 18-65 years of age (inclusive) * Body Mass Index (BMI) ≥ 18.0 and ≤ 35.0 kg/m2 * Documented physician-diagnosed asthma for ≥ 4 months prior to screening * Pre-bronchodilator FEV1 ≥ 70% predicted at screening * Documented allergy to at least one common allergen as confirmed by the skin prick test * Dual responder to inhaled bronchial allergen challenges as manifested by positive allergen-induced early (EAR) and late airway bronchoconstriction (LAR) at screening Key
Exclusion criteria
* Lung disease other than stable, mild asthma; e.g., worsening of asthma that requires a change in asthma therapy in the past 4 weeks or is deemed clinically significant by the investigator. * A diagnosed current or recent (within previous 8 weeks of screening, or prior to randomisation) bacterial, protozoal, viral or parasitic infection; is suspected of or is at high risk of having a parasitic infection, or has a history of more than one episode of herpes zoster infection. * Has a history of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest and/or hypoxic seizures. * Has been hospitalised or has attended the emergency room for asthma in the 12 months prior to screening, or prior to randomisation. * A history of tuberculosis (latent or active) or systemic fungal diseases. Part 2: Key Inclusion Criteria * Male or female, 40 to 75 years of age, inclusive, at the time of informed consent. * Confirmed diagnosis by a physician of COPD with symptoms compatible with COPD for at least 1 year prior to screening. * BMI ≥ 18.0 and ≤ 35.0 kg/m2 at screening. * Able to tolerate sputum induction and produce an adequate sputum sample with a neutrophil differential count \> 55% at screening. * Post-bronchodilator FEV1 ≥ 30% and ≤ 80% of the predicted normal, and post-bronchodilator FEV1/FVC \< 0.7 at the time of Screening. * Current or former tobacco smoker who has a smoking history of at least 10 pack years (Ten pack- years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years). * Has a negative result in the blood test for tuberculosis (TB) at screening. Key
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum percentage fall in FEV1 from pre-challenge between 3 and 8 hours (LAR) after administration of allergen inhalation challenge (Part 1). | Pre-challenge to between 3 and 8 hours after administration of allergen inhalation challenge |
| Change from baseline in percentage of neutrophils in sputum (Part 2). | Change from baseline to Day 22 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum percentage fall in FEV1 and AUC for the percent fall in FEV1 from pre-challenge between 0 and 2 hours after the administration of allergen inhalation challenge (EAR) (Part 1). | Pre-challenge to between 0 and 2 hours after the administration of allergen inhalation challenge | — |
| Maximum percentage fall in FEV1 and AUC for the percent fall in FEV1 between 0 and 8 hours (entire asthmatic response) after the administration of allergen inhalation challenge (Part 1) | Pre-challenge to between 0 and 8 hours after the administration of allergen inhalation challenge | — |
| Change from baseline in pre-challenge FEV1 (Part 1). | Change from baseline to Day 29 | — |
| Change from baseline in percentage of neutrophils (Part 2). | Change from baseline to Days 4, 8, 15, and 29 | — |
| Change from baseline in absolute and percentage cell counts for immune cells in induced sputum samples and blood (Part 2). | Change from baseline to Days 4, 8, 15, 22, and 29 | — |
| AUC for the percent fall in FEV1 from pre-challenge between 3 and 8 hours (LAR) after the administration of allergen inhalation challenge (Part 1). | Pre-challenge to between 3 and 8 hours after administration of allergen inhalation challenge | — |
| Change from baseline in pre- and post-bronchodilator impulse oscillometry (IOS) (Part 2). | Change from baseline to Days 4, 8, 15, 22, and 29 | — |
| Change from baseline in pre- and post-bronchodilator whole body plethysmography (Part 2). | Change from baseline to Days 4, 8, 15, 22, and 29 | — |
| Change from baseline in COPD Assessment Test (CAT) scores (Part 2). | Change from baseline to Days 4, 8, 15, 22, and 29 | Scores range from 0-40 with 40 being associated with the worst outcome. |
| Change from baseline in Breathlessness Cough and Sputum Scale (BCSS) scores (Part 2). | Change from baseline to Days 4, 8, 15, 22, and 29 | Scores range from 0-12 with 12 being associated with the worst outcome. |
| Change from baseline in FEV1 and post-bronchodilator FEV1 (Part 2). | Change from baseline to Days 4, 8, 15, 22, and 29 | — |
| Change from baseline and change during challenge in percentage of eosinophils in sputum (Part 1) | Change from baseline to 8 and 24 hours post allergen challenge | — |
Countries
United Kingdom
Outcome results
None listed