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

NCT05743075 | Completed Phase 3 FDA Drug

• 1 other identifier: RPL554-CPC001
• Study Type: interventional
• Target: 526
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Obstructive Pulmonary Disease

Outcome Measures

Primary Outcomes (1)

• 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

  12 weeks

Secondary Outcomes (14)

• Peak FEV1 over 4 hours post-dose at Week 12

  12 weeks

• Peak FEV1 at Week 6 and Week 24

  6 or 24 weeks

• Morning trough FEV1 at Week 6 and Week 24

  6 or 24 weeks

• Average FEV1 AUC0-4h at Week 6 and Week 24

  6 or 24 weeks

• Average FEV1 AUC0-4h at Week 12

  12 weeks

Study Arms (2)

Ensifentrine

EXPERIMENTAL

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.

Drug: Ensifentrine

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Ensifentrine DRUG

A dual PDE3/PDE 4 inhibitor

Ensifentrine

Placebo DRUG

Placebo solution

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Nuance Pharma (shanghai) Co., Ltd: lead
• Laboratory Corporation of America: collaborator

Study Sites (1)

1st Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

ensifentrine

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2023
• First Posted: February 24, 2023
• Study Start: March 10, 2023
• Primary Completion: December 6, 2024
• Study Completion: March 7, 2025
• Last Updated: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)