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
Overview
- Phase
- Phase 3
- Intervention
- Ensifentrine
- Conditions
- Chronic Obstructive Pulmonary Disease
- Sponsor
- Nuance Pharma (shanghai) Co., Ltd
- Enrollment
- 526
- Locations
- 1
- Primary Endpoint
- Average forced expiratory volume in 1 second (FEV1) area under the curve (AUC)0-12h
- Status
- Completed
- Last Updated
- 11 months ago
Overview
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.
Investigators
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.
Arms & Interventions
Ensifentrine
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: Ensifentrine
Placebo
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: Placebo
Outcomes
Primary Outcomes
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
Secondary Outcomes
- 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)
- Evening trough FEV1 at Week 12(12 weeks)
- Peak FEV1 at Week 6 and Week 24(6 or 24 weeks)
- Rescue medication use at Weeks 6, 12 and 24(6, 12 or 24 weeks)
- SGRQ total score at Weeks 6, 12 and 24(6, 12 or 24 weeks)
- Peak FEV1 over 4 hours post-dose at Week 12(12 weeks)
- Average FEV1 AUC0-4h at Week 12(12 weeks)
- Morning trough FEV1 at Week 12(12 weeks)
- Evaluating-Respiratory Symptoms (E-RS) Total Score at Weeks 6, 12 and 24(6, 12 or 24 weeks)
- SGRQ responder analysis at Weeks 6, 12 and 24(6, 12 or 24 weeks)
- TDI total score at Weeks 6, 12 and 24(6, 12 or 24 weeks)
- Average FEV1 AUC6-12h at Week 12(12 weeks)
- CAT total score at Weeks 6, 12 and 24(6, 12 or 24 weeks)