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A Phase 2a Study to Assess Safety, Daily Symptoms, PK, and Biomarkers of YPL-001 in COPD Patients

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

YPL-001 80 mg

YPL-001 160 mg

Placebo

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring COPD

Eligibility Criteria

30 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

UAB Lung Health Center
Florida Pulmonary Research Institute, LLC
Aventiv Research Inc.
Temple Lung Center, Temple University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Treatment A

Treatment B

Treatment C

Arm Description

Multiple oral YPL-001 80 mg doses (1 x 80 mg tablet + 1 x 1 YPL-001 80 mg matching placebo tablet) are administered approximately every 12 hours under fasting conditions for 55 consecutive days.

Multiple oral YPL-001 160 mg doses (2 x 80 mg tablets) are administered approximately every 12 hours under fasting conditions for 55 consecutive days.

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.

Outcomes

Primary Outcome Measures

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.

Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events

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.

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.

Secondary Outcome Measures

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.

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 Breathlessness(Dyspnea) Screen: 0(None)-10(Extreme): 0: better condition, 10: worse condition Sputum Quantity Screen: None(better)-greater than 1/4 cup(worse) Sputum Color Screen: White(better)-Brown(condition) Sputum Consistency Screen: Watery(better)-Thick(worse) Peak Flow Measurement Screen: 60(better)-800(worse) Symptoms Screen: (Temperature over 100F / Cough/Wheeze/Sore Throat/ Nasal Congestion) 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)

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)

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.

Full Information

NCT ID

NCT02272634

First Posted

October 12, 2014

Last Updated

July 11, 2023

Sponsor

Yungjin Pharm. Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT02272634

Brief Title

A Phase 2a Study to Assess Safety, Daily Symptoms, PK, and Biomarkers of YPL-001 in COPD Patients

Official Title

A Randomized, Double-Blind, Placebo Controlled, Multicenter 2a Study to Assess Safety, Daily Respiratory Symptoms, PK, and Biomarker Variations After Administration of Either YPL-001, or Placebo in Patients With Moderate-to-Severe COPD.

Study Type

Interventional

2. Study Status

Record Verification Date

June 2021

Overall Recruitment Status

Completed

Study Start Date

June 4, 2015 (Actual)

Primary Completion Date

November 8, 2017 (Actual)

Study Completion Date

November 8, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yungjin Pharm. Co., Ltd.

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Obstructive Pulmonary Disease

Keywords

COPD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

61 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment A

Arm Type

Experimental

Arm Description

Multiple oral YPL-001 80 mg doses (1 x 80 mg tablet + 1 x 1 YPL-001 80 mg matching placebo tablet) are administered approximately every 12 hours under fasting conditions for 55 consecutive days.

Arm Title

Treatment B

Arm Type

Experimental

Arm Description

Multiple oral YPL-001 160 mg doses (2 x 80 mg tablets) are administered approximately every 12 hours under fasting conditions for 55 consecutive days.

Arm Title

Treatment C

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

YPL-001 80 mg

Other Intervention Name(s)

Treatment A

Intervention Description

twice daily [BID]

Intervention Type

Drug

Intervention Name(s)

YPL-001 160 mg

Other Intervention Name(s)

Treatment B

Intervention Description

twice daily [BID]

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

twice daily [BID]

Primary Outcome Measure Information:

Title

Treatment-Emergent Adverse Event Frequency by Treatment - Number of Patients Reporting Events

Description

Time Frame

Up to Day 56

Title

Treatment-Emergent Adverse Event Frequency by Treatment - Adverse Events

Description

Time Frame

Up to Day 56

Title

Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Number of Patients Reporting Events

Description

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

Title

Treatment-Emergent Adverse Event Frequency by Treatment, Severity, and Relationship to Drug - Adverse Events

Description

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

Secondary Outcome Measure Information:

Title

Change From Baseline in Main Peak Expiratory Flow (PEF) Measured Daily

Description

Time Frame

Baseline to Day 55

Title

Change From Baseline of Symptom Severity Score for Symptoms of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

Description

Time Frame

Baseline to Day 55

Title

Change From Baseline in Dyspnea (Modified Borg Dyspnea Scale)

Description

Time Frame

Baseline to Day 55

Title

Change From Baseline of Calculated Score From Duke Activity Status Index (DASI)

Description

Time Frame

Baseline to Day 55

Other Pre-specified Outcome Measures:

Title

Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)

Description

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

Title

Change From Baseline in Inspiratory Capacity (IC)

Description

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

Title

Change From Baseline in Forced Expiratory Volume in 1 Second/Forced Vital Capacity (FEV1/FVC) Ratio

Description

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

Title

Transition Dyspnea Index (TDI) Focal Score

Description

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

Title

Change From Baseline in Chronic Obstructive Pulmonary Disease Assessment Test (CAT)

Description

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

Title

Change in Percentage of Total Cells in Bronchoalveolar Lavage (BAL)

Description

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

Title

Change in Concentrations of Inflammatory Marker in Bronchoalveolar Lavage (BAL)

Description

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

Title

Change in Percentage of Total Cells in Blood

Description

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

Title

Change in Concentrations of Inflammatory Marker in Plasma/Blood

Description

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

Title

Number of Participants With COPD Exacerbation

Description

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

Title

Change From Baseline in Forced Vital Capacity (FVC)

Description

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gerard J Criner, MD

Organizational Affiliation

Temple University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Mark T Dransfield, MD

Organizational Affiliation

The Kirklin Clinic of UAB Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

UAB Lung Health Center

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35249

Country

United States

Facility Name

Florida Pulmonary Research Institute, LLC

City

Winter Park

State/Province

Florida

ZIP/Postal Code

32789

Country

United States

Facility Name

Aventiv Research Inc.

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43213

Country

United States

Facility Name

Temple Lung Center, Temple University Hospital

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

191140

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

29496167

Citation

Lee SU, Lee S, Ro H, Choi JH, Ryu HW, Kim MO, Yuk HJ, Lee J, Hong ST, Oh SR. Piscroside C inhibits TNF-alpha/NF-kappaB pathway by the suppression of PKCdelta activity for TNF-RSC formation in human airway epithelial cells. Phytomedicine. 2018 Feb 1;40:148-157. doi: 10.1016/j.phymed.2018.01.012. Epub 2018 Jan 31.

Results Reference

derived

PubMed Identifier

28011397

Citation

Ryu HW, Lee SU, Lee S, Song HH, Son TH, Kim YU, Yuk HJ, Ro H, Lee CK, Hong ST, Oh SR. 3-Methoxy-catalposide inhibits inflammatory effects in lipopolysaccharide-stimulated RAW264.7 macrophages. Cytokine. 2017 Mar;91:57-64. doi: 10.1016/j.cyto.2016.12.006. Epub 2016 Dec 21.

Results Reference

derived

PubMed Identifier

26318254

Citation

Lee SU, Sung MH, Ryu HW, Lee J, Kim HS, In HJ, Ahn KS, Lee HJ, Lee HK, Shin DH, Lee Y, Hong ST, Oh SR. Verproside inhibits TNF-alpha-induced MUC5AC expression through suppression of the TNF-alpha/NF-kappaB pathway in human airway epithelial cells. Cytokine. 2016 Jan;77:168-75. doi: 10.1016/j.cyto.2015.08.262. Epub 2015 Aug 28.

Results Reference

derived

Learn more about this trial

A Phase 2a Study to Assess Safety, Daily Symptoms, PK, and Biomarkers of YPL-001 in COPD Patients

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