Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD
Brief summary
This is a Phase 2a, proof-of-concept, multicenter, randomized, double-blind, double dummy, 3-treatment, parallel study, with low and high YPL 001 doses (low dose and high dose twice daily \[BID\]) and a placebo control in moderate to severe Chronic Obstructive Pulmonary Disease (COPD) patients.
Detailed description
Treatments are described as follows: Treatment A: Multiple oral YPL-001 80 mg doses (1 x 80 mg tablet + 1 x 1 YPL-001 80 mg matching placebo tablet) will be administered approximately every 12 hours under fasting conditions for 55 consecutive days. Only the morning dose will be administered on Day 56. Treatment B: Multiple oral YPL-001 160 mg doses (2 x 80 mg tablets) will be administered approximately every 12 hours under fasting conditions for 55 consecutive days. Only the morning dose will be administered on Day 56. Treatment C: Multiple oral matching placebo (2 x 1 YPL-001 80 mg matching placebo tablets) will be administered approximately every 12 hours under fasting conditions for 55 consecutive days. Only the morning dose will be administered on Day 56. In all treatments, one tiotropium (Spiriva® HandiHaler®) 18 μg capsule will also be administered QD every morning prior to study drugs administration. Albuterol will be administered on an as needed basis. Each dose of Treatments A, B and C will be administered orally with approximately 240 mL of water.
Interventions
DRUGYPL-001 80 mg
twice daily \[BID\]
DRUGYPL-001 160 mg
twice daily \[BID\]
DRUGPlacebo
twice daily \[BID\]
Sponsors
Yungjin Pharm. Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Adult males and/or females, 30 to 85 years of age (inclusive). * History of COPD for at least 12 months prior to screening. * Diagnosed with COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines with symptoms compatible with COPD for at least 12 months prior to screening. * Classified as moderate to severe COPD based on the current severity classification GOLD Stage 2-3 disease in terms of post-bronchodilator spirometry at screening * etc.
Exclusion criteria
* History of life-threatening COPD including respiratory arrest, intensive care unit admission and/or requiring intubation. * History of more than 2 hospitalizations for COPD within 12 months prior to screening. * Presentation of an acute exacerbation of COPD that will be associated with increase sputum volume or change in sputum color within 4 weeks before Day 1 of the Run-in Period. * Evidence of pulmonary heart disease, or clinically significant pulmonary hypertension. * etc.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Up to Day 56 | When a patient experienced the same AE at more than one level of severity, the patient was counted once under the highest severity. |
| Treatment-Emergent Adverse Event Frequency by Treatment - Number of Patients Reporting Events | Up to Day 56 | A TEAE was defined as an AE that was starting or worsening at the time of or after study drug administration. All AEs collected by the clinics and recorded in the CRF were captured in the database and were listed in by-patient data listings. |
| Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Up to Day 56 | A TEAE was defined as an AE that was starting or worsening at the time of or after study drug administration. All AEs collected by the clinics and recorded in the CRF were captured in the database and were listed in by-patient data listings. |
| Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Up to Day 56 | When a patient experienced the same AE at more than one level of severity, the patient was counted once under the highest severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Main Peak Expiratory Flow (PEF) Measured Daily | Baseline to Day 55 | The PEF assessments are made daily prior to each dose from Day 1 of the Run-in Period to Day 56 of the Treatment Period. Three measurements were made at each time point using a hand held PEF meter. Readings not performed in the clinical research unit (CRU) were recorded in the patient e-diary. All PEF assessments were performed before administration of a bronchodilator where possible. Baseline is Day 1 predose measurement. |
| Change From Baseline of Symptom Severity Score for Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | Baseline to Day 55 | Patient is asked to record the major (sputum quality, color, consistency) and minor (cough, wheeze, sore throat, nasal congestion, discharge, and body temperature above 100°F) symptoms of COPD exacerbation via the e-diary before each dosing. Baseline is Day 1 predose measurement 1. Breathlessness(Dyspnea) Screen: 0(None)-10(Extreme): 0: better condition, 10: worse condition 2. Sputum Quantity Screen: None(better)-greater than 1/4 cup(worse) 3. Sputum Color Screen: White(better)-Brown(condition) 4. Sputum Consistency Screen: Watery(better)-Thick(worse) 5. Peak Flow Measurement Screen: 60(better)-800(worse) 6. Symptoms Screen: (Temperature over 100F / Cough/Wheeze/Sore Throat/ Nasal Congestion) 7. Nasal Discharge Screen(Yes/No) \* quantitative data were summarized including sample size, arithmetic mean, standard deviation, CV, min and max. Symptom score catecorizes normal(0-0.5), mild(1-1.5), moderate(2-2.5), severe(3-3.5) |
| Change From Baseline in Dyspnea (Modified Borg Dyspnea Scale) | Baseline to Day 55 | Severity level of patient's dyspnea is accessed via the modified Borg dyspnea scale programmed within the e-diary. The modified Borg dyspnea scale is a self-administered categorical scale with a score from 0 to 10, where 0 (as a measure of dyspnea) corresponds to the sensation of normal breathing (absence of dyspnea) and 10 corresponds to the patient's maximum possible sensation of dyspnea. |
| Change From Baseline of Calculated Score From Duke Activity Status Index (DASI) | Baseline to Day 55 | Patient's functional capacity and activity status were accessed via the DASI programmed within the e-diary. DASI is a self-administered 12-item questionnaire that assesses daily activities such as personal care, ambulation, household tasks, sexual function and recreation with respective metabolic costs. Each item has a specific weight based on the metabolic cost. The final score ranges between 0 and 58.2 points. The higher score shows the better the functional capacity. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Concentrations of Inflammatory Marker in Plasma/Blood | Baseline to Day 55 | The blood samples are collected at the the time points of the study for pharmacodynamics (PD) assessments of biomarkers. The blood samples are analyzed for concentrations of C-reactive protein (CRP), fibrinogen, TNF-α, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-13, MCP-1, and MMP-9. Baseline is Day 1 predose measurement. |
| Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Baseline (Screen) to Day 55 | Forced expiratory volume in 1 second (FEV1) is the amount of air that can be exhaled in one second. FEV1 is measured by spirometry performed at approximately the same time of day on each visit to avoid diurnal variation. A positive change from baseline in FEV1 indicates improvement in lung function. |
| Change From Baseline in Forced Vital Capacity (FVC) | Baseline (Screen) to Day 55 | Forced vital capacity (FVC) is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC is measured by spirometry performed at approximately the same time of day on each visit to avoid diurnal variation. A positive change from baseline in FVC indicates improvement in lung function. |
| Number of Participants With COPD Exacerbation | Baseline to Day 56 | Number of COPD exacerbation during 8-week treatment. COPD exacerbations are defined as a new onset or worsening of at least one respiratory symptom (i.e. dyspnea, cough, sputum purulence or volume, or wheeze) present for at least 3 consecutive days, documented change or increase in COPD-related treatment due to worsening symptoms or documented COPD-related hospitalizations or emergency room visits. |
| Change From Baseline in Inspiratory Capacity (IC) | Baseline (Screening) to Day 55 | Inspiratory capacity (IC) is the maximum volume of air that can be inhaled into the lungs from the normal resting position after breathing out normally. IC is measured by spirometry performed at approximately the same time of day on each visit to avoid diurnal variation. |
| Change From Baseline in Forced Expiratory Volume in 1 Second/Forced Vital Capacity (FEV1/FVC) Ratio | Baseline to Day 55 | The ratio is calculated as the amount of air expelled from the lungs in one second after a full inspiration (FEV1) divided by the volume of air that can forcibly be blown out after a full inspiration (FVC). |
| Transition Dyspnea Index (TDI) Focal Score | Baseline to Day 55 | Dyspnea at baseline (Day -1) will be assessed with the Baseline Dyspnea Index (BDI). This instrument has 3 domains (functional impairment, magnitude of task and magnitude of effort) with the values added for a combined focal score. Functional impairment determines the impact of breathlessness on the ability to carry out activities; magnitude of task determines the type of task that causes breathlessness, magnitude of effort establishes the level of effort that results in breathlessness. The BDI scores range from 0 (very severe impairment) to 4 (no impairment) for each domain with the baseline focal score consisting of the sum of each domain (0 to 12). Dyspnea throughout the study will be performed at the time points. The change from baseline is measured by the Transition Dyspnea Index (TDI) score which ranges from -3 (major deterioration) to +3 (major improvement) for each domain with the TDI focal score consisting in the sum of each domain (-9 to +9). |
| Change From Baseline in Chronic Obstructive Pulmonary Disease Assessment Test (CAT) | Baseline to Day 55 | The chronic obstructive pulmonary disease assessment test (CAT) is a short and simple questionnaire of 8 items completed by patients to be performed at the time points. Scores for each of the 8 items are summed to give a single, final score ranging from 0 (no impact on daily activities) to 40 (very high impact on daily activity). |
| Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | Baseline (Day -1) and Day 55 | The bronchoalveolar lavage (BAL) samples were collected at baseline and again at the completion of the study for pharmacodynamics (PD) assessments of biomarkers. BAL samples are at analyzed for total cell count (cells/mL) of white blood cell, macrophages, lymphocytes, neutrophils, and eosinophils as a percentage of total cells. |
| Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | Baseline (Day -1) and Day 55 | The bronchoalveolar lavage (BAL) samples are collected at baseline and again at the completion of the study for pharmacodynamics (PD) assessments of biomarkers. BAL samples are analyzed for concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-8, IL-13, Myeloperoxidase (MPO), neutrophil elastase (ELA2), monocyte chemotactic protein-1 (MCP-1), myeloperoxidase(MPO), and matrix metalloproteinase-9 (MMP-9). |
| Change in Percentage of Total Cells in Blood | Baseline to Day 55 | The blood samples are collected at the the time points of the study for pharmacodynamics (PD) assessments of biomarkers. The blood samples are analyzed for inflammatory markers (total and differential cell counts as absolute and percentage for neutrophils, macrophages, eosinophils and lymphocytes). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment A Multiple oral doses of YPL-001 80 mg BID on Days 1 - 55 and QD on Day 56 AM | 20 |
| Treatment B Multiple oral doses of YPL-001 160 mg BID on Days 1 - 55 and QD on Day 56 AM | 21 |
| Treatment C Multiple oral doses of placebo BID on Days 1 - 55 and QD on Day 56 AM | 20 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Treatment A | Treatment B | Treatment C | Total |
|---|---|---|---|---|
| Age, Continuous | 65.7 years STANDARD_DEVIATION 8.66 | 60.4 years STANDARD_DEVIATION 6.5 | 61.7 years STANDARD_DEVIATION 7.95 | 62.6 years STANDARD_DEVIATION 7.98 |
| Body mass index | 28.34 kg/m² STANDARD_DEVIATION 4.759 | 27.77 kg/m² STANDARD_DEVIATION 3.838 | 26.19 kg/m² STANDARD_DEVIATION 4.711 | 27.44 kg/m² STANDARD_DEVIATION 4.465 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 21 Participants | 20 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 6 Participants | 5 Participants | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 15 Participants | 15 Participants | 45 Participants |
| Region of Enrollment United States | 20 Participants | 21 Participants | 20 Participants | 61 Participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 9 Participants | 25 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 11 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 21 | 0 / 20 |
| other Total, other adverse events | 10 / 20 | 8 / 21 | 14 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 21 | 1 / 20 |
Outcome results
Primary
Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events
A TEAE was defined as an AE that was starting or worsening at the time of or after study drug administration. All AEs collected by the clinics and recorded in the CRF were captured in the database and were listed in by-patient data listings.
Time frame: Up to Day 56
Population: All available data for patients who received at least one dose of the investigational product (i.e., YPL-001) or placebo. Safety data for all discontinued patients included in this set for the time points for which their data are available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Total Number of AEs | 18 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Eye disorders | 1 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Gastrointestinal disorders | 3 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Infections and infestations | 5 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Injury, poisoning and procedural complications | 0 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Metabolism and nutrition disorders | 1 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Musculoskeletal and connective tissue disorders | 1 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Nervous system disorders | 0 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Respiratory, thoracic and mediastinal disorders | 5 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Skin and subcutaneous tissue disorders | 0 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Surgical and medical procedures | 1 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Vascular disorders | 1 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Vascular disorders | 0 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Total Number of AEs | 14 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Musculoskeletal and connective tissue disorders | 2 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Respiratory, thoracic and mediastinal disorders | 4 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Eye disorders | 1 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Metabolism and nutrition disorders | 0 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Surgical and medical procedures | 1 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Gastrointestinal disorders | 1 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Nervous system disorders | 1 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Injury, poisoning and procedural complications | 0 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Infections and infestations | 3 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Skin and subcutaneous tissue disorders | 1 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Infections and infestations | 6 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Injury, poisoning and procedural complications | 2 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Skin and subcutaneous tissue disorders | 1 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Metabolism and nutrition disorders | 0 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Musculoskeletal and connective tissue disorders | 0 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Nervous system disorders | 0 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Surgical and medical procedures | 0 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Total Number of AEs | 23 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Eye disorders | 0 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Respiratory, thoracic and mediastinal disorders | 13 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Gastrointestinal disorders | 1 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events | Vascular disorders | 0 Adverse events |
Primary
Treatment-Emergent Adverse Event Frequency by Treatment - Number of Patients Reporting Events
A TEAE was defined as an AE that was starting or worsening at the time of or after study drug administration. All AEs collected by the clinics and recorded in the CRF were captured in the database and were listed in by-patient data listings.
Time frame: Up to Day 56
Population: All available data for patients who received at least one dose of the investigational product (i.e., YPL-001) or placebo. Safety data for all discontinued patients included in this set for the time points for which their data are available.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment - Number of Patients Reporting Events | Number of Patients With AEs | 10 Participants |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment - Number of Patients Reporting Events | Number of Patients Without AEs | 10 Participants |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment - Number of Patients Reporting Events | Number of Patients With AEs | 8 Participants |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment - Number of Patients Reporting Events | Number of Patients Without AEs | 13 Participants |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment - Number of Patients Reporting Events | Number of Patients With AEs | 14 Participants |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment - Number of Patients Reporting Events | Number of Patients Without AEs | 6 Participants |
Primary
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events
When a patient experienced the same AE at more than one level of severity, the patient was counted once under the highest severity.
Time frame: Up to Day 56
Population: All available data for patients who received at least one dose of the investigational product (i.e., YPL-001) or placebo. Safety data for all discontinued patients included in this set for the time points for which their data are available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Relationship to Drug: Probable | 0 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Number of Adverse Events | 18 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Severity: Mild | 9 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Severity: Moderate | 9 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Severity: Severe | 0 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Relationship to Drug: Unrelated | 17 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Relationship to Drug: Unlikely | 0 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Relationship to Drug: Possible | 1 Adverse events |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Relationship to Drug: Definite | 0 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Relationship to Drug: Unrelated | 12 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Relationship to Drug: Definite | 0 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Number of Adverse Events | 14 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Relationship to Drug: Probable | 0 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Relationship to Drug: Possible | 0 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Severity: Mild | 8 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Severity: Severe | 0 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Relationship to Drug: Unlikely | 2 Adverse events |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Severity: Moderate | 6 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Relationship to Drug: Unlikely | 0 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Severity: Severe | 1 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Relationship to Drug: Probable | 0 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Relationship to Drug: Unrelated | 23 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Relationship to Drug: Definite | 0 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Severity: Moderate | 11 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Number of Adverse Events | 23 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Severity: Mild | 11 Adverse events |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events | Relationship to Drug: Possible | 0 Adverse events |
Primary
Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events
When a patient experienced the same AE at more than one level of severity, the patient was counted once under the highest severity.
Time frame: Up to Day 56
Population: All available data for patients who received at least one dose of the investigational product (i.e., YPL-001) or placebo. Safety data for all discontinued patients included in this set for the time points for which their data are available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Severity: Severe | 0 participants |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Relationship to Drug: Definite | 0 participants |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Relationship to Drug: Unlikely | 0 participants |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Relationship to Drug: Unrelated | 9 participants |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Number of Patients With AEs | 10 participants |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Relationship to Drug: Probable | 0 participants |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Severity: Moderate | 7 participants |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Severity: Mild | 3 participants |
| Treatment A | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Relationship to Drug: Possible | 1 participants |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Relationship to Drug: Unrelated | 7 participants |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Number of Patients With AEs | 8 participants |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Severity: Mild | 3 participants |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Severity: Moderate | 5 participants |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Severity: Severe | 0 participants |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Relationship to Drug: Unlikely | 1 participants |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Relationship to Drug: Possible | 0 participants |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Relationship to Drug: Probable | 0 participants |
| Treatment B | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Relationship to Drug: Definite | 0 participants |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Severity: Moderate | 9 participants |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Number of Patients With AEs | 14 participants |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Relationship to Drug: Possible | 0 participants |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Severity: Mild | 4 participants |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Relationship to Drug: Definite | 0 participants |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Relationship to Drug: Unrelated | 14 participants |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Severity: Severe | 1 participants |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Relationship to Drug: Probable | 0 participants |
| Treatment C | Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events | Relationship to Drug: Unlikely | 0 participants |
Secondary
Change From Baseline in Dyspnea (Modified Borg Dyspnea Scale)
Severity level of patient's dyspnea is accessed via the modified Borg dyspnea scale programmed within the e-diary. The modified Borg dyspnea scale is a self-administered categorical scale with a score from 0 to 10, where 0 (as a measure of dyspnea) corresponds to the sensation of normal breathing (absence of dyspnea) and 10 corresponds to the patient's maximum possible sensation of dyspnea.
Time frame: Baseline to Day 55
Population: All available data for patients who received at least one dose of the investigational product (i.e., YPL-001) or placebo. Symptom monitoring data for all discontinued patients were included in this set for the time points for which their data are available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | Change From Baseline in Dyspnea (Modified Borg Dyspnea Scale) | Baseline (Day 1) | 3.88 units on a scale | Standard Deviation 1.996 |
| Treatment A | Change From Baseline in Dyspnea (Modified Borg Dyspnea Scale) | Day 55 | 3.76 units on a scale | Standard Deviation 2.463 |
| Treatment B | Change From Baseline in Dyspnea (Modified Borg Dyspnea Scale) | Baseline (Day 1) | 4.05 units on a scale | Standard Deviation 1.746 |
| Treatment B | Change From Baseline in Dyspnea (Modified Borg Dyspnea Scale) | Day 55 | 3.88 units on a scale | Standard Deviation 2.147 |
| Treatment C | Change From Baseline in Dyspnea (Modified Borg Dyspnea Scale) | Baseline (Day 1) | 3.18 units on a scale | Standard Deviation 2.512 |
| Treatment C | Change From Baseline in Dyspnea (Modified Borg Dyspnea Scale) | Day 55 | 3.31 units on a scale | Standard Deviation 2.323 |
Secondary
Change From Baseline in Main Peak Expiratory Flow (PEF) Measured Daily
The PEF assessments are made daily prior to each dose from Day 1 of the Run-in Period to Day 56 of the Treatment Period. Three measurements were made at each time point using a hand held PEF meter. Readings not performed in the clinical research unit (CRU) were recorded in the patient e-diary. All PEF assessments were performed before administration of a bronchodilator where possible. Baseline is Day 1 predose measurement.
Time frame: Baseline to Day 55
Population: Analysis population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | Change From Baseline in Main Peak Expiratory Flow (PEF) Measured Daily | Day55 | 282.8 L/min | Standard Deviation 123.61 |
| Treatment A | Change From Baseline in Main Peak Expiratory Flow (PEF) Measured Daily | Baseline (Day1) | 250.0 L/min | Standard Deviation 109.82 |
| Treatment B | Change From Baseline in Main Peak Expiratory Flow (PEF) Measured Daily | Day55 | 277.9 L/min | Standard Deviation 92.08 |
| Treatment B | Change From Baseline in Main Peak Expiratory Flow (PEF) Measured Daily | Baseline (Day1) | 254.9 L/min | Standard Deviation 68.61 |
| Treatment C | Change From Baseline in Main Peak Expiratory Flow (PEF) Measured Daily | Day55 | 247.6 L/min | Standard Deviation 96.17 |
| Treatment C | Change From Baseline in Main Peak Expiratory Flow (PEF) Measured Daily | Baseline (Day1) | 240.7 L/min | Standard Deviation 68.21 |
Secondary
Change From Baseline of Calculated Score From Duke Activity Status Index (DASI)
Patient's functional capacity and activity status were accessed via the DASI programmed within the e-diary. DASI is a self-administered 12-item questionnaire that assesses daily activities such as personal care, ambulation, household tasks, sexual function and recreation with respective metabolic costs. Each item has a specific weight based on the metabolic cost. The final score ranges between 0 and 58.2 points. The higher score shows the better the functional capacity.
Time frame: Baseline to Day 55
Population: All available data for patients who received at least one dose of the investigational product (i.e., YPL-001) or placebo. Symptom monitoring data for all discontinued patients included in this set for the time points for which their data are available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Change From Baseline of Calculated Score From Duke Activity Status Index (DASI) | -0.267 score on a scale | Standard Deviation 3.7696 |
| Treatment B | Change From Baseline of Calculated Score From Duke Activity Status Index (DASI) | -2.844 score on a scale | Standard Deviation 9.8016 |
| Treatment C | Change From Baseline of Calculated Score From Duke Activity Status Index (DASI) | 1.137 score on a scale | Standard Deviation 4.8336 |
Secondary
Change From Baseline of Symptom Severity Score for Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
Patient is asked to record the major (sputum quality, color, consistency) and minor (cough, wheeze, sore throat, nasal congestion, discharge, and body temperature above 100°F) symptoms of COPD exacerbation via the e-diary before each dosing. Baseline is Day 1 predose measurement 1. Breathlessness(Dyspnea) Screen: 0(None)-10(Extreme): 0: better condition, 10: worse condition 2. Sputum Quantity Screen: None(better)-greater than 1/4 cup(worse) 3. Sputum Color Screen: White(better)-Brown(condition) 4. Sputum Consistency Screen: Watery(better)-Thick(worse) 5. Peak Flow Measurement Screen: 60(better)-800(worse) 6. Symptoms Screen: (Temperature over 100F / Cough/Wheeze/Sore Throat/ Nasal Congestion) 7. Nasal Discharge Screen(Yes/No) \* quantitative data were summarized including sample size, arithmetic mean, standard deviation, CV, min and max. Symptom score catecorizes normal(0-0.5), mild(1-1.5), moderate(2-2.5), severe(3-3.5)
Time frame: Baseline to Day 55
Population: All available data for patients who received at least one dose of the investigational product (i.e., YPL-001) or placebo. Symptom monitoring data for all discontinued patients were included in this set for the time points for which their data are available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | Change From Baseline of Symptom Severity Score for Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | Baseline (Day 1) | 0.63 score on a scale | Standard Deviation 0.812 |
| Treatment A | Change From Baseline of Symptom Severity Score for Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | Day 55 | 0.26 score on a scale | Standard Deviation 0.504 |
| Treatment B | Change From Baseline of Symptom Severity Score for Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | Baseline (Day 1) | 0.17 score on a scale | Standard Deviation 0.297 |
| Treatment B | Change From Baseline of Symptom Severity Score for Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | Day 55 | 0.18 score on a scale | Standard Deviation 0.351 |
| Treatment C | Change From Baseline of Symptom Severity Score for Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | Baseline (Day 1) | 0.47 score on a scale | Standard Deviation 0.757 |
| Treatment C | Change From Baseline of Symptom Severity Score for Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | Day 55 | 0.50 score on a scale | Standard Deviation 0.876 |
Other Pre-specified
Change From Baseline in Chronic Obstructive Pulmonary Disease Assessment Test (CAT)
The chronic obstructive pulmonary disease assessment test (CAT) is a short and simple questionnaire of 8 items completed by patients to be performed at the time points. Scores for each of the 8 items are summed to give a single, final score ranging from 0 (no impact on daily activities) to 40 (very high impact on daily activity).
Time frame: Baseline to Day 55
Population: Analysis population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Change From Baseline in Chronic Obstructive Pulmonary Disease Assessment Test (CAT) | -1.2 units on a scale | Standard Deviation 6.14 |
| Treatment B | Change From Baseline in Chronic Obstructive Pulmonary Disease Assessment Test (CAT) | -1.3 units on a scale | Standard Deviation 5.11 |
| Treatment C | Change From Baseline in Chronic Obstructive Pulmonary Disease Assessment Test (CAT) | 0.0 units on a scale | Standard Deviation 7.38 |
Other Pre-specified
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Forced expiratory volume in 1 second (FEV1) is the amount of air that can be exhaled in one second. FEV1 is measured by spirometry performed at approximately the same time of day on each visit to avoid diurnal variation. A positive change from baseline in FEV1 indicates improvement in lung function.
Time frame: Baseline (Screen) to Day 55
Population: Analysis population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | -0.088 L | Standard Deviation 0.2721 |
| Treatment B | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | -0.002 L | Standard Deviation 0.1974 |
| Treatment C | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | 0.011 L | Standard Deviation 0.1533 |
Other Pre-specified
Change From Baseline in Forced Expiratory Volume in 1 Second/Forced Vital Capacity (FEV1/FVC) Ratio
The ratio is calculated as the amount of air expelled from the lungs in one second after a full inspiration (FEV1) divided by the volume of air that can forcibly be blown out after a full inspiration (FVC).
Time frame: Baseline to Day 55
Population: Analysis population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Change From Baseline in Forced Expiratory Volume in 1 Second/Forced Vital Capacity (FEV1/FVC) Ratio | -1.8 ratio | Standard Deviation 6.21 |
| Treatment B | Change From Baseline in Forced Expiratory Volume in 1 Second/Forced Vital Capacity (FEV1/FVC) Ratio | -0.2 ratio | Standard Deviation 4.63 |
| Treatment C | Change From Baseline in Forced Expiratory Volume in 1 Second/Forced Vital Capacity (FEV1/FVC) Ratio | 2.0 ratio | Standard Deviation 4.98 |
Other Pre-specified
Change From Baseline in Forced Vital Capacity (FVC)
Forced vital capacity (FVC) is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC is measured by spirometry performed at approximately the same time of day on each visit to avoid diurnal variation. A positive change from baseline in FVC indicates improvement in lung function.
Time frame: Baseline (Screen) to Day 55
Population: Analysis population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Change From Baseline in Forced Vital Capacity (FVC) | -0.087 L | Standard Deviation 0.3475 |
| Treatment B | Change From Baseline in Forced Vital Capacity (FVC) | 0.007 L | Standard Deviation 0.229 |
| Treatment C | Change From Baseline in Forced Vital Capacity (FVC) | -0.105 L | Standard Deviation 0.3117 |
Other Pre-specified
Change From Baseline in Inspiratory Capacity (IC)
Inspiratory capacity (IC) is the maximum volume of air that can be inhaled into the lungs from the normal resting position after breathing out normally. IC is measured by spirometry performed at approximately the same time of day on each visit to avoid diurnal variation.
Time frame: Baseline (Screening) to Day 55
Population: Analysis population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Change From Baseline in Inspiratory Capacity (IC) | -0.158 L | Standard Deviation 0.3148 |
| Treatment B | Change From Baseline in Inspiratory Capacity (IC) | -0.097 L | Standard Deviation 0.4357 |
| Treatment C | Change From Baseline in Inspiratory Capacity (IC) | -0.304 L | Standard Deviation 0.4709 |
Other Pre-specified
Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL)
The bronchoalveolar lavage (BAL) samples are collected at baseline and again at the completion of the study for pharmacodynamics (PD) assessments of biomarkers. BAL samples are analyzed for concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-8, IL-13, Myeloperoxidase (MPO), neutrophil elastase (ELA2), monocyte chemotactic protein-1 (MCP-1), myeloperoxidase(MPO), and matrix metalloproteinase-9 (MMP-9).
Time frame: Baseline (Day -1) and Day 55
Population: All patients who received at least one dose of YPL-001 or placebo and provide at least one post-baseline PD measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | MCP-1 | 90.05 % change from baseline | Standard Deviation 224.213 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-5 | 49.97 % change from baseline | Standard Deviation 161.255 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | MPO | 64.14 % change from baseline | Standard Deviation 243.237 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-8 | 50.61 % change from baseline | Standard Deviation 178.116 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-6 | -7.41 % change from baseline | Standard Deviation 79.289 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | ELA2(neutrophil elastage) | 46.36 % change from baseline | Standard Deviation 154.476 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-1ß | 79.65 % change from baseline | Standard Deviation 216.674 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-13 | 34.47 % change from baseline | Standard Deviation 187.126 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | MMP-9 | 28.38 % change from baseline | Standard Deviation 201.899 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-4 | 11.12 % change from baseline | Standard Deviation 101.995 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | TNF-a | 14.04 % change from baseline | Standard Deviation 114.456 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-6 | 130.15 % change from baseline | Standard Deviation 354.531 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | ELA2(neutrophil elastage) | 714.18 % change from baseline | Standard Deviation 1864.367 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-13 | 321.42 % change from baseline | Standard Deviation 1168.485 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-1ß | 223.62 % change from baseline | Standard Deviation 618.896 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-4 | 121.13 % change from baseline | Standard Deviation 258.496 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-5 | 220.88 % change from baseline | Standard Deviation 523.979 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-8 | 173.57 % change from baseline | Standard Deviation 600.987 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | MCP-1 | 155.50 % change from baseline | Standard Deviation 601.606 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | MMP-9 | 565.88 % change from baseline | Standard Deviation 2067.142 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | MPO | 275.50 % change from baseline | Standard Deviation 693.932 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | TNF-a | 268.19 % change from baseline | Standard Deviation 863.815 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | MPO | 62.14 % change from baseline | Standard Deviation 199.545 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | MCP-1 | 252.95 % change from baseline | Standard Deviation 816.196 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-1ß | 45.43 % change from baseline | Standard Deviation 207.504 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | ELA2(neutrophil elastage) | 155.57 % change from baseline | Standard Deviation 523.538 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | MMP-9 | 43.31 % change from baseline | Standard Deviation 242.912 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-13 | 160.25 % change from baseline | Standard Deviation 243.317 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-6 | 53.48 % change from baseline | Standard Deviation 153.791 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-5 | 213.86 % change from baseline | Standard Deviation 341.157 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | TNF-a | 124.20 % change from baseline | Standard Deviation 266.423 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-8 | 45.40 % change from baseline | Standard Deviation 222.303 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL) | IL-4 | 155.36 % change from baseline | Standard Deviation 276.287 |
Other Pre-specified
Change in Concentrations of Inflammatory Marker in Plasma/Blood
The blood samples are collected at the the time points of the study for pharmacodynamics (PD) assessments of biomarkers. The blood samples are analyzed for concentrations of C-reactive protein (CRP), fibrinogen, TNF-α, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-13, MCP-1, and MMP-9. Baseline is Day 1 predose measurement.
Time frame: Baseline to Day 55
Population: All patients who received at least one dose of YPL-001 or placebo and provide at least one post-baseline PD measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | Change in Concentrations of Inflammatory Marker in Plasma/Blood | CRP | -12.087 % change from baseline | Standard Deviation 102.3304 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Plasma/Blood | MMP9 | -10.922 % change from baseline | Standard Deviation 52.3542 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-6 | -26.0682 % change from baseline | Standard Deviation 36.92257 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-1ß | 44.9813 % change from baseline | Standard Deviation 149.88595 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Plasma/Blood | MCP1 | 20.019 % change from baseline | Standard Deviation 86.8398 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-8 | 26.916 % change from baseline | Standard Deviation 47.0832 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Plasma/Blood | ELA2 | -7.13 % change from baseline | Standard Deviation 30.726 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-13 | 5.158 % change from baseline | Standard Deviation 45.4151 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Plasma/Blood | TNF-α | -10.499 % change from baseline | Standard Deviation 24.7753 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-4 | 68.849 % change from baseline | Standard Deviation 280.7619 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Plasma/Blood | Fibrinogen | 0.5 % change from baseline | Standard Deviation 15.39 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Plasma/Blood | MPO | -6.051 % change from baseline | Standard Deviation 21.3202 |
| Treatment A | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-5 | 73.36 % change from baseline | Standard Deviation 214.724 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-8 | 6.986 % change from baseline | Standard Deviation 54.7421 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Plasma/Blood | ELA2 | -17.01 % change from baseline | Standard Deviation 33.05 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-13 | 10.197 % change from baseline | Standard Deviation 53.7029 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-1ß | 32.7901 % change from baseline | Standard Deviation 121.71539 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-4 | 22.678 % change from baseline | Standard Deviation 98.3923 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-5 | 20.57 % change from baseline | Standard Deviation 257.416 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-6 | -35.8383 % change from baseline | Standard Deviation 82.30541 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Plasma/Blood | MCP1 | -13.923 % change from baseline | Standard Deviation 31.9128 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Plasma/Blood | MMP9 | -9.087 % change from baseline | Standard Deviation 39.4842 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Plasma/Blood | MPO | -9.661 % change from baseline | Standard Deviation 26.7605 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Plasma/Blood | TNF-α | -16.184 % change from baseline | Standard Deviation 25.6551 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Plasma/Blood | CRP | 29.028 % change from baseline | Standard Deviation 345.0216 |
| Treatment B | Change in Concentrations of Inflammatory Marker in Plasma/Blood | Fibrinogen | -0.4 % change from baseline | Standard Deviation 13.88 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Plasma/Blood | MMP9 | -27.524 % change from baseline | Standard Deviation 34.844 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-4 | -19.865 % change from baseline | Standard Deviation 35.6127 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Plasma/Blood | CRP | -61.732 % change from baseline | Standard Deviation 40.0405 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Plasma/Blood | MPO | -14.232 % change from baseline | Standard Deviation 26.6217 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-1ß | 4.7453 % change from baseline | Standard Deviation 72.39394 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Plasma/Blood | ELA2 | -26.33 % change from baseline | Standard Deviation 30.972 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Plasma/Blood | TNF-α | -1.585 % change from baseline | Standard Deviation 27.552 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-8 | 57.464 % change from baseline | Standard Deviation 176.8141 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-6 | -48.4230 % change from baseline | Standard Deviation 51.59468 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-13 | -1.622 % change from baseline | Standard Deviation 5.5691 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Plasma/Blood | MCP1 | 51.441 % change from baseline | Standard Deviation 173.5531 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Plasma/Blood | IL-5 | -5.30 % change from baseline | Standard Deviation 99.117 |
| Treatment C | Change in Concentrations of Inflammatory Marker in Plasma/Blood | Fibrinogen | -7.7 % change from baseline | Standard Deviation 22.38 |
Other Pre-specified
Change in Percentage of Total Cells in Blood
The blood samples are collected at the the time points of the study for pharmacodynamics (PD) assessments of biomarkers. The blood samples are analyzed for inflammatory markers (total and differential cell counts as absolute and percentage for neutrophils, macrophages, eosinophils and lymphocytes).
Time frame: Baseline to Day 55
Population: All patients who received at least one dose of YPL-001 or placebo and provide at least one post-baseline PD measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | Change in Percentage of Total Cells in Blood | Monocytes | 0.05858 % change from baseline | Standard Deviation 24.446709 |
| Treatment A | Change in Percentage of Total Cells in Blood | Lymphocytes | 10.21926 % change from baseline | Standard Deviation 35.449159 |
| Treatment A | Change in Percentage of Total Cells in Blood | WBC | 5.229 % change from baseline | Standard Deviation 23.1568 |
| Treatment A | Change in Percentage of Total Cells in Blood | Eosinophils | 7.61728 % change from baseline | Standard Deviation 78.203389 |
| Treatment A | Change in Percentage of Total Cells in Blood | Neutrophils | 1.62215 % change from baseline | Standard Deviation 24.058407 |
| Treatment B | Change in Percentage of Total Cells in Blood | Lymphocytes | -1.58746 % change from baseline | Standard Deviation 23.45521 |
| Treatment B | Change in Percentage of Total Cells in Blood | WBC | -2.289 % change from baseline | Standard Deviation 22.8687 |
| Treatment B | Change in Percentage of Total Cells in Blood | Eosinophils | 20.06903 % change from baseline | Standard Deviation 91.240833 |
| Treatment B | Change in Percentage of Total Cells in Blood | Monocytes | 30.65211 % change from baseline | Standard Deviation 65.329419 |
| Treatment B | Change in Percentage of Total Cells in Blood | Neutrophils | 0.13700 % change from baseline | Standard Deviation 10.8890617 |
| Treatment C | Change in Percentage of Total Cells in Blood | Neutrophils | -3.29570 % change from baseline | Standard Deviation 10.559662 |
| Treatment C | Change in Percentage of Total Cells in Blood | Monocytes | 1.67563 % change from baseline | Standard Deviation 46.936967 |
| Treatment C | Change in Percentage of Total Cells in Blood | WBC | -5.572 % change from baseline | Standard Deviation 21.1569 |
| Treatment C | Change in Percentage of Total Cells in Blood | Lymphocytes | 14.24407 % change from baseline | Standard Deviation 26.363322 |
| Treatment C | Change in Percentage of Total Cells in Blood | Eosinophils | 57.36857 % change from baseline | Standard Deviation 226.50576 |
Other Pre-specified
Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL)
The bronchoalveolar lavage (BAL) samples were collected at baseline and again at the completion of the study for pharmacodynamics (PD) assessments of biomarkers. BAL samples are at analyzed for total cell count (cells/mL) of white blood cell, macrophages, lymphocytes, neutrophils, and eosinophils as a percentage of total cells.
Time frame: Baseline (Day -1) and Day 55
Population: All patients who received at least one dose of YPL-001 or placebo and provide at least one post-baseline PD measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A | Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | Macrophages | 45.9 percent change from baseline | Standard Deviation 136.88 |
| Treatment A | Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | Lymphocytes | 37.8 percent change from baseline | Standard Deviation 111.26 |
| Treatment A | Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | WBC | 5.2 percent change from baseline | Standard Deviation 23.16 |
| Treatment A | Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | Eosinohils | -50.8 percent change from baseline | Standard Deviation 49.25 |
| Treatment A | Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | Neutrophils | 57.0 percent change from baseline | Standard Deviation 152.7 |
| Treatment B | Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | Lymphocytes | 2.7 percent change from baseline | Standard Deviation 75.89 |
| Treatment B | Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | WBC | -2.3 percent change from baseline | Standard Deviation 22.87 |
| Treatment B | Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | Eosinohils | 38.3 percent change from baseline | Standard Deviation 150.97 |
| Treatment B | Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | Macrophages | 9.3 percent change from baseline | Standard Deviation 55.48 |
| Treatment B | Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | Neutrophils | 83.5 percent change from baseline | Standard Deviation 252.98 |
| Treatment C | Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | Neutrophils | 1.1 percent change from baseline | Standard Deviation 106.19 |
| Treatment C | Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | Macrophages | 59.8 percent change from baseline | Standard Deviation 124.05 |
| Treatment C | Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | WBC | -5.6 percent change from baseline | Standard Deviation 21.16 |
| Treatment C | Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | Lymphocytes | 19.4 percent change from baseline | Standard Deviation 121.45 |
| Treatment C | Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL) | Eosinohils | 61.2 percent change from baseline | Standard Deviation 261.73 |
Other Pre-specified
Number of Participants With COPD Exacerbation
Number of COPD exacerbation during 8-week treatment. COPD exacerbations are defined as a new onset or worsening of at least one respiratory symptom (i.e. dyspnea, cough, sputum purulence or volume, or wheeze) present for at least 3 consecutive days, documented change or increase in COPD-related treatment due to worsening symptoms or documented COPD-related hospitalizations or emergency room visits.
Time frame: Baseline to Day 56
Population: Analysis population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A | Number of Participants With COPD Exacerbation | 3 Participants |
| Treatment B | Number of Participants With COPD Exacerbation | 2 Participants |
| Treatment C | Number of Participants With COPD Exacerbation | 5 Participants |
Other Pre-specified
Transition Dyspnea Index (TDI) Focal Score
Dyspnea at baseline (Day -1) will be assessed with the Baseline Dyspnea Index (BDI). This instrument has 3 domains (functional impairment, magnitude of task and magnitude of effort) with the values added for a combined focal score. Functional impairment determines the impact of breathlessness on the ability to carry out activities; magnitude of task determines the type of task that causes breathlessness, magnitude of effort establishes the level of effort that results in breathlessness. The BDI scores range from 0 (very severe impairment) to 4 (no impairment) for each domain with the baseline focal score consisting of the sum of each domain (0 to 12). Dyspnea throughout the study will be performed at the time points. The change from baseline is measured by the Transition Dyspnea Index (TDI) score which ranges from -3 (major deterioration) to +3 (major improvement) for each domain with the TDI focal score consisting in the sum of each domain (-9 to +9).
Time frame: Baseline to Day 55
Population: Analysis population included data obtained from all the subjects who were enrolled in the study and received at least one dose of the investigational drug and had primary efficacy endpoint after administration of the investigational drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Transition Dyspnea Index (TDI) Focal Score | 2.2 units on a scale | Standard Deviation 2.68 |
| Treatment B | Transition Dyspnea Index (TDI) Focal Score | 1.1 units on a scale | Standard Deviation 2.75 |
| Treatment C | Transition Dyspnea Index (TDI) Focal Score | 2.9 units on a scale | Standard Deviation 2.84 |