Chronic Obstructive Pulmonary DiseasePhase 3NCT05743075
A Study to Evaluate the Efficacy and Safety of Ensifentrine for 24 Weeks in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease
A Phase 3 study testing Ensifentrine in people with Chronic Obstructive Pulmonary Disease, run by Nuance Pharma (shanghai) Co., Ltd at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- Ensifentrine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 526 participants
- Where
- 1 siteChina
- Study dates
- 10 Mar 2023to 7 Mar 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Show all 9Show fewer
- 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.
Who cannot join
- 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;.
Show all 22Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
1st Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong
About this study
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
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.
Read the 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.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- Ensifentrine, Placebo
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnsifentrineDrug
A dual PDE3/PDE 4 inhibitor
PlaceboDrug
Placebo solution
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 weeks
Secondary outcomes (14)
Peak FEV1 over 4 hours post-dose at Week 12
Change from baseline of Peak FEV1 over 4 hours post-dose at Week 12
Measured: 12 weeks
Peak FEV1 at Week 6 and Week 24
Change from baseline peak FEV1
Measured: 6 or 24 weeks
Morning trough FEV1 at Week 6 and Week 24
Change from baseline morning trough FEV1
Measured: 6 or 24 weeks
Average FEV1 AUC0-4h at Week 6 and Week 24
Change from baseline average FEV1 AUC0-4h
Measured: 6 or 24 weeks
Average FEV1 AUC0-4h at Week 12
Change from baseline average FEV1 AUC0-4h
Measured: 12 weeks
Morning trough FEV1 at Week 12
Change from baseline of morning trough FEV1 at Week 12
Measured: 12 weeks
Evening trough FEV1 at Week 12
Change from baseline of evening trough FEV1 at Week 12
Measured: 12 weeks
Average FEV1 AUC6-12h at Week 12
Change from baseline of Average FEV1 AUC6-12h at Week 12
Measured: 12 weeks
Rescue medication use at Weeks 6, 12 and 24
Change from baseline of Rescue medication use
Measured: 6, 12 or 24 weeks
Evaluating-Respiratory Symptoms (E-RS) Total Score at Weeks 6, 12 and 24
Change from baseline of Evaluating-Respiratory Symptoms (E-RS) Total Score
Measured: 6, 12 or 24 weeks
SGRQ total score at Weeks 6, 12 and 24
Change from baseline of SGRQ total score
Measured: 6, 12 or 24 weeks
SGRQ responder analysis at Weeks 6, 12 and 24
Change from baseline of SGRQ responder analysis
Measured: 6, 12 or 24 weeks
TDI total score at Weeks 6, 12 and 24
Change from baseline of TDI total score
Measured: 6, 12 or 24 weeks
CAT total score at Weeks 6, 12 and 24
Change from baseline of CAT total score
Measured: 6, 12 or 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2023
- Study start10 Mar 2023
- Primary completion6 Dec 2024
- Study completion7 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 526 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nuance Pharma (shanghai) Co., Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Laboratory Corporation of America
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05743075
- Sponsor's protocol ID
- RPL554-CPC001
- Status last verified
- May 2025
- First submitted
- 14 Feb 2023
- Last updated
- 4 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zhou Y, Chen C, Wang Z, Wu F, Tian D, Xiao Z, Cao J, Xu F, Gao J, Chen J, Peng L, Dai Y, Dong L, Hu Y, Yang T, Liu C, Wang L, Liu X, Yang T, Yang G, Zhu D, Wei Z, Gu W, Ran P, Zhong N; ENHANCE-CHINA Investigators. Efficacy and Safety of Ensifentrine in Chinese Participants With COPD: The ENHANCE-CHINA Randomized Clinical Trial. Chest. 2026 Jul;170(1):88-100. doi: 10.1016/j.chest.2026.02.035. Epub 2026 Mar 25.
PubMed 41895581
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05743075
- Acronym / sponsor ID
- RPL554-CPC001
- Conditions
- Chronic Obstructive Pulmonary Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 526 participants (actual)
- Lead sponsor
- Nuance Pharma (shanghai) Co., LtdIndustry (pharma, biotech, devices)
- Collaborators
- Laboratory Corporation of America
- Study start
- 10 Mar 2023 (actual)
- Primary completion
- 6 Dec 2024 (actual)
- Study completion
- 7 Mar 2025 (actual)
- First posted
- 24 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ensifentrine | Experimental | Drug: EnsifentrineEligible 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. |
| Placebo | Placebo comparator | Drug: PlaceboEligible 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. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (22 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EnsifentrineA dual PDE3/PDE 4 inhibitor | Drug | Ensifentrine |
| PlaceboPlacebo solution | Drug | Placebo |
Primary outcome
Average forced expiratory volume in 1 second (FEV1) area under the curve (AUC)0-12h
Time frame: 12 weeks
Change from baseline of Average forced expiratory volume in 1 second (FEV1) area under the curve (AUC)0-12h
14 secondary outcomes
Peak FEV1 over 4 hours post-dose at Week 12
Time frame: 12 weeks
Peak FEV1 at Week 6 and Week 24
Time frame: 6 or 24 weeks
Morning trough FEV1 at Week 6 and Week 24
Time frame: 6 or 24 weeks
Average FEV1 AUC0-4h at Week 6 and Week 24
Time frame: 6 or 24 weeks
Average FEV1 AUC0-4h at Week 12
Time frame: 12 weeks
Morning trough FEV1 at Week 12
Time frame: 12 weeks
Evening trough FEV1 at Week 12
Time frame: 12 weeks
Average FEV1 AUC6-12h at Week 12
Time frame: 12 weeks
Rescue medication use at Weeks 6, 12 and 24
Time frame: 6, 12 or 24 weeks
Evaluating-Respiratory Symptoms (E-RS) Total Score at Weeks 6, 12 and 24
Time frame: 6, 12 or 24 weeks
SGRQ total score at Weeks 6, 12 and 24
Time frame: 6, 12 or 24 weeks
SGRQ responder analysis at Weeks 6, 12 and 24
Time frame: 6, 12 or 24 weeks
TDI total score at Weeks 6, 12 and 24
Time frame: 6, 12 or 24 weeks
CAT total score at Weeks 6, 12 and 24
Time frame: 6, 12 or 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2025.
- Derived from this study: PubMed 41895581Zhou Y, Chen C, Wang Z, Wu F, Tian D, Xiao Z, Cao J, Xu F, Gao J, Chen J, Peng L, Dai Y, Dong L, Hu Y, Yang T, Liu C, Wang L, Liu X, Yang T, Yang G, Zhu D, Wei Z, Gu W, Ran P, Zhong N; ENHANCE-CHINA Investigators. Efficacy and Safety of Ensifentrine in Chinese Participants With COPD: The ENHANCE-CHINA Randomized Clinical Trial. Chest. 2026 Jul;170(1):88-100. doi: 10.1016/j.chest.2026.02.035. Epub 2026 Mar 25.
- Individual participant dataSharing planned: No
Related trials for Chronic Obstructive Pulmonary Disease
Active, not recruiting
Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS
COPD, Smoking
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruiting
The Aim of the Study is to Decipher the Alterations in Signalling Pathways of Skeletal Muscle Stem Cells (Satellite Cells (SCs)) in Individuals With COPD, as Well as to Examine the Effect of Exercise Training on SCs.
COPD (Chronic Obstructive Pulmonary Disease), Sarcopenia in Elderly
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Belumosudil Compared With Best Available Therapy in Participants Aged 12 Years or Older With Chronic Graft-versus-host Disease
Chronic Graft Versus Host Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ensifentrine in people with Chronic Obstructive Pulmonary Disease, run by Nuance Pharma (shanghai) Co., Ltd at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average forced expiratory volume in 1 second (FEV1) area under the curve (AUC)0-12h (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05743075, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2025.