Part 1: Asthma Part 2: Chronic Obstructive Pulmonary Disease (COPD) MedDRA version: 20.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders 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: SelK2
Product Code: SelK2
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Humanized anti-PSGL-1 monoclonal antibody
Current Sponsor code: SelK2
Concentration unit: mg/ml
Sponsors
Tetherex Pharmaceuticals Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part 1: 1.Subject’s written informed consent obtained prior to any study-related procedure. 2.Male or female, 18 to 65 years of age, inclusive, at the time of informed consent. 3.Female subjects must be either of non-childbearing potential or if of childbearing potential use a highly effective birth control method (See Section 9.4.2). 4.Female subjects must agree not to donate ova/oocytes during the study and for 6 months after the last dose of investigational Medicinal Product (IMP). 5.Male subjects (with partners of child-bearing potential) must use highly effective contraception (See Section 9.4.1). 6.Male subjects must agree not to donate semen during the study and for 3 months after the last dose of IMP. 7.Body Mass Index (BMI) = 18.0 and = 35.0 kg/m2 at Screening. 8.Documented physician-diagnosed asthma for = 4 months prior to screening. 9.Pre-bronchodilator FEV1 = 70% predicted at screening. 10.Documented allergy to at least one common allergen as confirmed by the skin prick test, with wheal diameter =3mm greater than the negative control. Historical data up to one year prior to screening can be used. 11.Dual responder to inhaled bronchial allergen challenges as manifested by positive allergen-induced early (EAR) and late airway bronchoconstriction (LAR) at screening, defined as follows: •EAR is defined as a fall in FEV1 of at least 20% from pre-challenge post diluent baseline values during the 30 minutes after inhaled bronchial allergen challenge; •LAR is defined by a fall from post diluent value of FEV1 of at least 15% on at least 3 occasions, 2 of which must be consecutive, between 3 to 8 hours after inhaled allergen challenge. 12.Sputum producer stratum only (minimum of 20 of the 36 planned subjects): Subject is able to tolerate sputum induction and produce adequate sputum after bronchial allergen challenge during the screening period (either at the 8?hour or 24?hour post allergen time points). 13.No clinically significant abnormalities as determined by the investigator in the results of laboratory evaluations at screening. 14.Clinical findings from the 12-lead ECG or vital signs that are deemed medically acceptable as determined by the investigator at Screening and prior to randomisation. 15.Has a negative result in the blood test for tuberculosis (TB) at screening. 16.Understands the study procedures in the informed consent form (ICF) and is willing and able to comply with the protocol-defined study procedures, restrictions and expectations. Part 2: 1.Subject’s written informed consent obtained prior to any study-related procedure. 2.Male or female, 40 to 75 years of age, inclusive, at the time of informed consent. 3.Confirmed diagnosis by a physician of COPD with symptoms compatible with COPD for at least 1 year prior to screening. 4.Female subjects must be either of non-childbearing potential or if of childbearing potential use a highly effective birth control method (See Section 9.4.2). 5.Female subjects must agree not to donate ova/oocytes during the study and for 6 months after the last dose of IMP. 6.Male subjects (with partners of child-bearing potential) must use highly effective contraception (See Section 9.4.1). 7.Male subjects must agree not to donate semen during the study and for 3 months after the last dose of IMP. 8.BMI = 18.0 and = 35.0 kg/m2 at screening. 9.Able to tolerate sputum induction and produce an adequate sputum sample with a neutrophil differential count > 55% at screening. 10.Post-bronc
Exclusion criteria
Exclusion criteria: Part 1. -Lung disease other than stable, mild asthma; worsening of asthma that requires a change in asthma therapy in the past 4 weeks or is deemed clinically significant (CS). -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 last 12 months. -Positive urine cotinine test result at screening or prior to randomisation. -Uses or has used tobacco or nicotine-containing products within 12 months prior to screening, or prior to randomisation. -Smoking history of a cumulative tobacco exposure of > 5 pack years. Part 2. -COPD exacerbation requiring oral steroids &/or antibiotics, within the last 8 weeks. -A positive sputum culture at Screening indicating ongoing infection. -Other respiratory disorders other than COPD. -A history of life-threatening COPD including ICU admission &/or requiring intubation within the last 5 years. -A history of > 1 hospitalisation for COPD in the previous 1 year. -Evidence of cor pulmonale or CS pulmonary hypertension. -Current clinically significant sleep apnoea requiring non-invasive ventilation or supplemental oxygen during sleep. -Previous lung resection, lung reduction surgery or lung transplantation. -Requires supplemental oxygen, even on an occasional basis. -Active participation in a pulmonary rehabilitation program. -Inability to perform impulse oscillometry, whole body plethysmography or technically acceptable spirometry. Parts 1 & 2 -History of CS hypotensive episodes or symptoms of fainting, dizziness, or light-headedness. -History of lymphoma, leukemia, or other types of malignancy except for completely resected squamous/basal cell cancer. -Any infection requiring hospitalisation or intravenous antibiotics within 6 months. -A diagnosed current or recent (within 8 weeks) bacterial, protozoal, viral, parasitic infection; is suspected of or is at high risk of having a parasitic infection or has a history of > 1 episode of herpes zoster infection. -Evidence of current or previous CS disease with the exception of stable, mild asthma (Part 1) or stable COPD (Part 2). -Has an eGFR of <60 mL/min/1.73m2 at screening, based on MDRD equation. -Has had major surgery in the last 2 months or is anticipating surgery during the study or follow-up period -History of any drug or alcohol abuse in the past 2 years. -Positive breath alcohol results at screening, or prior to randomisation. -Positive urine drugs of abuse test result (unless this can be explained by the subject’s current medications) at screening or prior to randomisation. -History of hypersensitivity to drugs, latex allergy, band aids, adhesive dressing, or medical tape, with a CS reaction. -History of serious adverse reaction, severe hypersensitivity or allergy to any drug or in any other circumstance. -Females with a positive pregnancy test at screening, or prior to randomisation, or who are lactating. -Has received treatment with a live vaccine within 3 months prior to screening, or prior to randomisation. -Positive HBsAg, HCV Ab or HIV results. Subjects who are HBs antibody positive or HB core antibody positive are not excluded provided the HBsAg result is negative. Subjects who are HCV Ab positive are not excluded if a subsequent HCV RNA test is negative. -A history of TB (latent or active) or systemic fungal diseases. -Receiving any of the proh
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Part 1 - Secondary •Evaluate SelK2 for its ability to reduce the LAR in terms of area under the curve (AUC) for the FEV1 after inhaled allergen challenge. •Evaluate the effect of SelK2 on the eosinophil percentage in sputum. •Evaluate the effect of SelK2 on the early asthmatic response (EAR) after inhaled allergen challenge. •Evaluate the effect of SelK2 on the overall asthmatic response from 0-8 hours after inhaled allergen challenge. •Evaluate the effect of SelK2 on pre-challenge FEV1. •Evaluate the overall safety and tolerability of 2 doses of intravenous SelK2. •Further describe the Pharmacokinetics (PK - study drug levels and the time it takes for your body to break down the study drug) and Pharmacodynamics (PD; inhibition of PSGL-1/P-selectin binding) of SelK2 after giving 2 doses. •Evaluate the immunogenicity (Human Anti-Human Antibody [HAHA] response) following 2 doses of SelK2. To see if the body is making antibodies against the study medication. Part 1 - Exploratory •Evaluat;Primary end point(s): Part 1: •Maximum percentage fall in FEV1 from pre-challenge between 3 and 8 hours (LAR) after administration of allergen inhalation challenge. Part 2: •Change from baseline in percentage of neutrophils in sputum on Day 22.;Timepoint(s) of evaluation of this end point: Part 1: •FEV1 measured at Day 36 from pre-allergen challenge and the period beginning 3 hours and ending 8 hours after the allergen challenge. Part 2: Days 22;Main Objective: Part 1 Evaluate SelK2 for its ability to reduce the late asthmatic response (LAR) in terms of maximum percentage fall in FEV1 (forced expiratory volume in one second) after inhaled allergen challenge (breathing in a fine mist of the allergen that the participant is sensitive to). Part 2 Evaluate the effect of SelK2 on neutrophil percentage in sputum (phelgm). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 Secondary: 1. AUC for the percent fall in FEV1 from pre-challenge between 3 and 8 hours (LAR) after the administration of allergen inhalation challenge. 2. Change from baseline and change during challenge in percentage of eosinophils in sputum measured at 8 and 24 hours post allergen challenge. 3. 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). 4. 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. 5. Change from baseline in pre-challenge FEV1. Part 1 Exploratory: 6. Change from baseline and change during challenge in absolute and percentage cell counts for immune cells in induced sputum samples and blood (except for eosinophils in sputum which is a secondary endpoint). 7. Change from baseline and change during challenge in fractional exhaled nitric oxide. 8. Change from baseline and change during challenge in biomarkers of inflammation in both sputum and blood. 9. Change in subject reported outcome as captured by Asthma Control Questionnaire 5-Question Version (ACQ-5) Score. Part 2 Secondary: 1. Change from baseline in percentage of neutrophils on Day 4, 8, 15, and 29. 2. Change from baseline in absolute and percentage cell counts for immune cells in induced sputum samples and blood (except for neutrophils in sputum which is the primary endpoint) on Days 4, 8, 15, 22, 29. 3. Change from baseline in FEV1 and post-bronchodilator FEV1 on Days 4, 8, 15, 22, and 29. 4. Change from baseline in pre- and post-bronchodilator impulse oscillometry (IOS) on Days 4, 8, 15, 22, and 29. 5. Change from baseline in pre- and post-bronchodilator Whole body plethysmography on Days 4, 8, 15, 22, and 29. 6. Change from baseline for subject reported outcomes: COPD Assessment Test (CAT) scores and Breathlessness Cough and Sputum | — |
Countries
United Kingdom
Contacts
Public ContactJonathan Stocker
Tetherex Pharmaceuticals Corporation
Outcome results
None listed