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A Study to Evaluate the Efficacy and Safety of Ensifentrine for 24 Weeks in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Ensifentrine
Placebo
Sponsored by
Nuance Pharma (shanghai) Co., Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patient must be 40 to 80 years of age inclusive, at the time of Screening, male or female; Current or former cigarette smokers with a history of cigarette smoking ≥ 10 pack-years; Patients with a clear clinical history of COPD and related symptoms prior to screening; Patients with moderately to severe COPD: Pre- and Post- salbutamol FEV1/FVC ratio < 0.70; and Post-salbutamol FEV1 ≥ 30% and ≤ 70% of predicted A score of ≥2 on the Modified Medical Research Council Dyspnea Scale at screening; Patients on no maintenance/background therapy or patients on stable maintenance as either LAMA or LABA therapy. Short-acting β2 agonists (SABAs) should be withheld for at least 6 hours prior to initiation of any spirometry; Female subjects of childbearing potential must have a negative blood pregnancy test 7 days prior to randomization and not be pregnant or lactating. Female subjects of childbearing potential and male subjects with partners of childbearing potential are required to use at least one effective contraceptive method (such as intrauterine contraceptive device, contraceptives or condom) from the screening period, throughout the study period and for at least 30 days after the last dose of blinded investigational product. Exclusion Criteria: History of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation; Hospitalizations for COPD, pneumonia, or Corona Virus Disease 2019 (COVID-19) in the 12 weeks prior to Screening and/or COPD exacerbation, Newly-occurring pneumonia, a positive COVID-19 test result indicating an active infection before Screening; Patients with lower respiratory tract infection occurred and not resolved within 6 weeks prior to screening and/or prior to randomization; COPD exacerbation requiring oral or parenteral (intravenous, subcutaneous, or intramuscular injection) steroids within 3 months prior to screening; Previous lung resection, OR lung reduction surgery within 1 year of screening; Patients with long term of oxygen use;. Patients with pulmonary rehabilitation; Patients with other respiratory disorders including, but not limited to, current diagnosis of asthma, active tuberculosis, lung cancer, sarcoidosis, pulmonary fibrosis, interstitial lung disease, unstable sleep apnea, known alpha-1 antitrypsin deficiency, cor pulmonale, clinically significant pulmonary hypertension, clinically significant bronchiectasis, or other active pulmonary disease; Major surgery (requiring general anesthesia) within 6 weeks prior to screening; Historical or current evidence of clinically significant cardiovascular disease defined as any disease that in the opinion of the Investigator would put the safety of the patient at risk through participation or which could affect the efficacy or safety analysis if the disease/condition were to exacerbate during the study. Chronic uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, psychiatric, or ophthalmic diseases that the investigator believes are clinically significant; Unstable liver disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices or persistent jaundice, cirrhosis, known biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones); History of malignancy within the past 5 years (except for cured basal cell carcinoma or squamous cell carcinoma of skin, cervical carcinoma in situ), or current potential malignancy under evaluation; Abnormal findings on physical examination that an investigator considers to be clinically significant at screening; Chest X-ray (CXR; posterior-anterior) at screening, or in the 12 months prior to screening with clinically significant abnormalities not attributable to COPD; Electrocardiogram (ECG) finding that is significantly abnormal at Screening; Abnormal lab test result, such as eGFR < 30 mL/min, ALT ≥ 2 × upper limit of normal (ULN), alkaline phosphatase and/or bilirubin > 1.5 × ULN, or any other abnormal hematology, biochemistry, or viral serology deemed by an investigator to be clinically significantly abnormal; Use of an experimental drug within 30 days or 5 half-lives prior to screening (whichever is longer), and/or participation in an interventional clinical trial within 30 days prior to screening; Use of an investigational medical device or participation as a subject in a medical device clinical trial within 30 days prior to screening; Intolerance or hypersensitivity to salbutamol or Ensifentrine (RPL554) or any of its excipients/components; Use of traditional Chinese medicine within 2 weeks prior to first dose of Ensifentrine/ Placebo, which with antispasmodic and anti-asthmatic effects and interfering with respirometry test,that would interfere with the study based on the investigator's discretion; Any other reason that the Investigator considers makes the patient unsuitable to participate.

Sites / Locations

  • 1st Affiliated Hospital of Guangzhou Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ensifentrine

Placebo

Arm Description

Eligible subjects will be randomly assigned in a 5:3 ratio to receive either Ensifentrine or placebo. Doses and methods of administration are as follows: Ensifentrine (RPL554) 3 mg BID or placebo BID will be administered by aerosol inhalation for 24 weeks; each nebulization time wil be approximately 5 minutes.

Eligible subjects will be randomly assigned in a 5:3 ratio to receive either Ensifentrine or placebo. Doses and methods of administration are as follows: Ensifentrine (RPL554) 3 mg BID or placebo BID will be administered by aerosol inhalation for 24 weeks; each nebulization time wil be approximately 5 minutes.

Outcomes

Primary Outcome Measures

Average forced expiratory volume in 1 second (FEV1) area under the curve (AUC)0-12h
Change from baseline of Average forced expiratory volume in 1 second (FEV1) area under the curve (AUC)0-12h

Secondary Outcome Measures

Peak FEV1 over 4 hours post-dose at Week 12
Change from baseline of Peak FEV1 over 4 hours post-dose at Week 12
Peak FEV1 at Week 6 and Week 24
Change from baseline peak FEV1
Morning trough FEV1 at Week 6 and Week 24
Change from baseline morning trough FEV1
Average FEV1 AUC0-4h at Week 6 and Week 24
Change from baseline average FEV1 AUC0-4h
Average FEV1 AUC0-4h at Week 12
Change from baseline average FEV1 AUC0-4h
Morning trough FEV1 at Week 12
Change from baseline of morning trough FEV1 at Week 12
Evening trough FEV1 at Week 12
Change from baseline of evening trough FEV1 at Week 12
Average FEV1 AUC6-12h at Week 12
Change from baseline of Average FEV1 AUC6-12h at Week 12
Rescue medication use at Weeks 6, 12 and 24
Change from baseline of Rescue medication use
Evaluating-Respiratory Symptoms (E-RS) Total Score at Weeks 6, 12 and 24
Change from baseline of Evaluating-Respiratory Symptoms (E-RS) Total Score
SGRQ total score at Weeks 6, 12 and 24
Change from baseline of SGRQ total score
SGRQ responder analysis at Weeks 6, 12 and 24
Change from baseline of SGRQ responder analysis
TDI total score at Weeks 6, 12 and 24
Change from baseline of TDI total score
CAT total score at Weeks 6, 12 and 24
Change from baseline of CAT total score

Full Information

First Posted
February 14, 2023
Last Updated
March 29, 2023
Sponsor
Nuance Pharma (shanghai) Co., Ltd
Collaborators
Laboratory Corporation of America
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1. Study Identification

Unique Protocol Identification Number
NCT05743075
Brief Title
A Study to Evaluate the Efficacy and Safety of Ensifentrine for 24 Weeks in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease
Official Title
A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Study to Evaluate the Efficacy and Safety of Ensifentrine Over 24 Weeks in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 10, 2023 (Actual)
Primary Completion Date
November 1, 2024 (Anticipated)
Study Completion Date
February 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nuance Pharma (shanghai) Co., Ltd
Collaborators
Laboratory Corporation of America

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical study, which aims to evaluate the efficacy, safety, and PK characteristics of Ensifentrine 3 mg twice daily (BID) for 24 weeks treatment of moderate to severe COPD.
Detailed Description
The study is divided into 3 periods, a screening/run-in period (run-in for 28 days), a treatment period (24 weeks), and a follow-up period (1 week after the end-of-treatment visit). The qualified subjects will be randomly assigned to the Ensifentrine group or placebo group in a ratio of 5:3, stratified by maintenance therapy in a stable background long-acting muscarinic antagonist (LAMA) or long-acting β2 agonist (LABA) (yes or no) and smoking status (current or past smokers). The Ensifentrine group will receive Ensifentrine 3mg BID nebulizer, and the placebo group will receive placebo nebulizer. The treatment will be lasted given for 24 weeks in both groups. During treatment, lung function, COPD symptoms, quality of life and other parameters of subjects will be assessed at baseline, week 6, 12, and 24, and the safety will also be assessed over 24-week treatment period and the follow-up period. PK characteristics and dose-response relationship of Ensifentrine will be analyzed for all patients using sparse sampling.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
488 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ensifentrine
Arm Type
Experimental
Arm Description
Eligible subjects will be randomly assigned in a 5:3 ratio to receive either Ensifentrine or placebo. Doses and methods of administration are as follows: Ensifentrine (RPL554) 3 mg BID or placebo BID will be administered by aerosol inhalation for 24 weeks; each nebulization time wil be approximately 5 minutes.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Eligible subjects will be randomly assigned in a 5:3 ratio to receive either Ensifentrine or placebo. Doses and methods of administration are as follows: Ensifentrine (RPL554) 3 mg BID or placebo BID will be administered by aerosol inhalation for 24 weeks; each nebulization time wil be approximately 5 minutes.
Intervention Type
Drug
Intervention Name(s)
Ensifentrine
Intervention Description
A dual PDE3/PDE 4 inhibitor
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo solution
Primary Outcome Measure Information:
Title
Average forced expiratory volume in 1 second (FEV1) area under the curve (AUC)0-12h
Description
Change from baseline of Average forced expiratory volume in 1 second (FEV1) area under the curve (AUC)0-12h
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Peak FEV1 over 4 hours post-dose at Week 12
Description
Change from baseline of Peak FEV1 over 4 hours post-dose at Week 12
Time Frame
12 weeks
Title
Peak FEV1 at Week 6 and Week 24
Description
Change from baseline peak FEV1
Time Frame
6 or 24 weeks
Title
Morning trough FEV1 at Week 6 and Week 24
Description
Change from baseline morning trough FEV1
Time Frame
6 or 24 weeks
Title
Average FEV1 AUC0-4h at Week 6 and Week 24
Description
Change from baseline average FEV1 AUC0-4h
Time Frame
6 or 24 weeks
Title
Average FEV1 AUC0-4h at Week 12
Description
Change from baseline average FEV1 AUC0-4h
Time Frame
12 weeks
Title
Morning trough FEV1 at Week 12
Description
Change from baseline of morning trough FEV1 at Week 12
Time Frame
12 weeks
Title
Evening trough FEV1 at Week 12
Description
Change from baseline of evening trough FEV1 at Week 12
Time Frame
12 weeks
Title
Average FEV1 AUC6-12h at Week 12
Description
Change from baseline of Average FEV1 AUC6-12h at Week 12
Time Frame
12 weeks
Title
Rescue medication use at Weeks 6, 12 and 24
Description
Change from baseline of Rescue medication use
Time Frame
6, 12 or 24 weeks
Title
Evaluating-Respiratory Symptoms (E-RS) Total Score at Weeks 6, 12 and 24
Description
Change from baseline of Evaluating-Respiratory Symptoms (E-RS) Total Score
Time Frame
6, 12 or 24 weeks
Title
SGRQ total score at Weeks 6, 12 and 24
Description
Change from baseline of SGRQ total score
Time Frame
6, 12 or 24 weeks
Title
SGRQ responder analysis at Weeks 6, 12 and 24
Description
Change from baseline of SGRQ responder analysis
Time Frame
6, 12 or 24 weeks
Title
TDI total score at Weeks 6, 12 and 24
Description
Change from baseline of TDI total score
Time Frame
6, 12 or 24 weeks
Title
CAT total score at Weeks 6, 12 and 24
Description
Change from baseline of CAT total score
Time Frame
6, 12 or 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient must be 40 to 80 years of age inclusive, at the time of Screening, male or female; Current or former cigarette smokers with a history of cigarette smoking ≥ 10 pack-years; Patients with a clear clinical history of COPD and related symptoms prior to screening; Patients with moderately to severe COPD: Pre- and Post- salbutamol FEV1/FVC ratio < 0.70; and Post-salbutamol FEV1 ≥ 30% and ≤ 70% of predicted A score of ≥2 on the Modified Medical Research Council Dyspnea Scale at screening; Patients on no maintenance/background therapy or patients on stable maintenance as either LAMA or LABA therapy. Short-acting β2 agonists (SABAs) should be withheld for at least 6 hours prior to initiation of any spirometry; Female subjects of childbearing potential must have a negative blood pregnancy test 7 days prior to randomization and not be pregnant or lactating. Female subjects of childbearing potential and male subjects with partners of childbearing potential are required to use at least one effective contraceptive method (such as intrauterine contraceptive device, contraceptives or condom) from the screening period, throughout the study period and for at least 30 days after the last dose of blinded investigational product. Exclusion Criteria: History of life-threatening COPD including Intensive Care Unit admission and/or requiring intubation; Hospitalizations for COPD, pneumonia, or Corona Virus Disease 2019 (COVID-19) in the 12 weeks prior to Screening and/or COPD exacerbation, Newly-occurring pneumonia, a positive COVID-19 test result indicating an active infection before Screening; Patients with lower respiratory tract infection occurred and not resolved within 6 weeks prior to screening and/or prior to randomization; COPD exacerbation requiring oral or parenteral (intravenous, subcutaneous, or intramuscular injection) steroids within 3 months prior to screening; Previous lung resection, OR lung reduction surgery within 1 year of screening; Patients with long term of oxygen use;. Patients with pulmonary rehabilitation; Patients with other respiratory disorders including, but not limited to, current diagnosis of asthma, active tuberculosis, lung cancer, sarcoidosis, pulmonary fibrosis, interstitial lung disease, unstable sleep apnea, known alpha-1 antitrypsin deficiency, cor pulmonale, clinically significant pulmonary hypertension, clinically significant bronchiectasis, or other active pulmonary disease; Major surgery (requiring general anesthesia) within 6 weeks prior to screening; Historical or current evidence of clinically significant cardiovascular disease defined as any disease that in the opinion of the Investigator would put the safety of the patient at risk through participation or which could affect the efficacy or safety analysis if the disease/condition were to exacerbate during the study. Chronic uncontrolled disease including, but not limited to, endocrine, active hyperthyroidism, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, psychiatric, or ophthalmic diseases that the investigator believes are clinically significant; Unstable liver disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices or persistent jaundice, cirrhosis, known biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones); History of malignancy within the past 5 years (except for cured basal cell carcinoma or squamous cell carcinoma of skin, cervical carcinoma in situ), or current potential malignancy under evaluation; Abnormal findings on physical examination that an investigator considers to be clinically significant at screening; Chest X-ray (CXR; posterior-anterior) at screening, or in the 12 months prior to screening with clinically significant abnormalities not attributable to COPD; Electrocardiogram (ECG) finding that is significantly abnormal at Screening; Abnormal lab test result, such as eGFR < 30 mL/min, ALT ≥ 2 × upper limit of normal (ULN), alkaline phosphatase and/or bilirubin > 1.5 × ULN, or any other abnormal hematology, biochemistry, or viral serology deemed by an investigator to be clinically significantly abnormal; Use of an experimental drug within 30 days or 5 half-lives prior to screening (whichever is longer), and/or participation in an interventional clinical trial within 30 days prior to screening; Use of an investigational medical device or participation as a subject in a medical device clinical trial within 30 days prior to screening; Intolerance or hypersensitivity to salbutamol or Ensifentrine (RPL554) or any of its excipients/components; Use of traditional Chinese medicine within 2 weeks prior to first dose of Ensifentrine/ Placebo, which with antispasmodic and anti-asthmatic effects and interfering with respirometry test,that would interfere with the study based on the investigator's discretion; Any other reason that the Investigator considers makes the patient unsuitable to participate.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mengde Wang
Phone
86-21-32035318
Email
mengde.wang@nuancepharma.cn
Facility Information:
Facility Name
1st Affiliated Hospital of Guangzhou Medical University
City
Guangzhou
State/Province
Guangdong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yumin Zhou, Dr
First Name & Middle Initial & Last Name & Degree
Nanshan Zhong, Prof

12. IPD Sharing Statement

Plan to Share IPD
No

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A Study to Evaluate the Efficacy and Safety of Ensifentrine for 24 Weeks in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease

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