Ensifentrine for COPD
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Verona Pharma plc
Must be taking: Bronchodilators
Disqualifiers: Asthma, Lung diseases, Cancer, others
No Placebo Group
Prior Safety Data
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?This is a randomized, double-blind, placebo-controlled, two-period cross-over study of nebulized ensifentrine (3 mg) or placebo administered BID for two 8-week Treatment Periods. All participants with receive both ensifentrine and placebo during participation. There are 7 in-clinic visits over a total duration of up to 24 weeks participation.
Will I have to stop taking my current medications?
The trial requires participants to use the study-supplied COPD Maintenance Therapy once daily, but it does not specify if you must stop other medications. It's best to discuss your current medications with the study team to understand any specific requirements.
What data supports the effectiveness of the drug Ensifentrine for COPD?
Ensifentrine has shown to improve lung function and reduce the rate of moderate or severe exacerbations in patients with COPD, as demonstrated in Phase III trials. It also improved symptoms and quality of life in some studies, with a safety profile similar to placebo.
12345Is Ensifentrine safe for humans?
Ensifentrine has been tested in clinical trials for COPD and has shown a satisfactory safety profile, with fewer effects on heart rate and blood pressure compared to some other treatments, and no significant side effects reported.
12367What makes the drug Ensifentrine unique for treating COPD?
Ensifentrine is unique because it is an inhaled drug that acts as a dual inhibitor of phosphodiesterase (PDE) 3 and 4, providing both bronchodilator (helps open airways) and anti-inflammatory effects, which is different from most current COPD treatments that focus mainly on bronchodilation or inflammation separately.
12348Eligibility Criteria
This trial is for COPD patients aged 40-80 who have a history of smoking and moderate to severe lung function impairment. They must be using regular bronchodilator therapy, able to use a nebulizer correctly, and produce sputum samples. Exclusions include significant liver enzyme elevations, recent cancer (except certain skin cancers), immunodeficiency, recent experimental drug/device use or other serious health issues.Inclusion Criteria
COPD Severity: Pre- and Post-albuterol/salbutamol FEV1/FVC ratio of <0.70; Post-albuterol/salbutamol FEV1 ≥30 % and ≤80% of predicted normal calculated using the National Health and Nutrition Examination Survey III.
Regular use of bronchodilator COPD therapy, in any form (e.g., LAMA, LABA, LAMA+LABA), for at least 4 weeks prior to Screening and agrees to use study supplied COPD Maintenance Therapy once daily through the final study visit.
You are between 40 and 80 years old, have smoked at least 10 packs of cigarettes in your life, and have been diagnosed with COPD based on specific guidelines.
+1 more
Exclusion Criteria
Alanine aminotransferase (ALT) ≥ 2 x upper limit of normal (ULN), alkaline phosphatase and/or bilirubin > 1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). HIV infection or other immunodeficiency. History of cancer within the last 5 years, except for well-treated basal cell carcinoma and squamous cell carcinoma of the skin.
Taking prohibited medication. Prior receipt of blinded nebulized study medication in an ensifentrine (RPL554) study. Note: Other ensifentrine formats (e.g., DPI, MPI) are not exclusionary.
Use of an experimental drug within 30 days or 5 half-lives of Screening, whichever is longer, and/or participation in a study treatment-free follow-up phase of a clinical trial within 30 days prior to Screening. Use of an experimental medical device or participation in a follow-up phase of an experimental medical device clinical trial within 30 days prior to Screening. Any other medical history, chronic uncontrolled diseases that the investigator considers clinically significant, examination or laboratory findings or reason that the Investigator considers makes the patient unsuitable to participate at Screening.
+2 more
Trial Timeline
Screening and Run-in
Participants are screened for eligibility to participate in the trial and enter a run-in period to ensure a stable background on a once daily COPD Maintenance Therapy
2-4 weeks
1 visit (in-person)
Treatment Period 1
Participants receive 8 weeks of treatment with blinded, nebulized ensifentrine or placebo + once daily COPD Maintenance Therapy
8 weeks
3 visits (in-person)
Washout
Participants will only take once daily COPD Maintenance Therapy. There will be a follow-up phone call about 1 week after finishing Treatment Period 1
4 weeks
Treatment Period 2
Participants receive 8 weeks of treatment with Study Medication (opposite of Treatment Period 1) + once daily COPD Maintenance Therapy
8 weeks
3 visits (in-person)
Safety Follow-up
Safety follow-up call 1 week after Treatment Period 2
1 week
Participant Groups
The study tests the effect of ensifentrine versus placebo on inflammation in COPD patients. It's a double-blind study where participants receive both treatments across two periods totaling up to 24 weeks with seven clinic visits. Ensifentrine is administered twice daily via nebulization.
2Treatment groups
Experimental Treatment
Group I: Treatment Sequence 2Experimental Treatment2 Interventions
Treatment Period 1 (blinded Placebo) followed by Treatment Period 2 (blinded Ensifentrine)
Group II: Treatment Sequence 1Experimental Treatment2 Interventions
Treatment Period 1 (blinded Ensifentrine) followed by Treatment Period 2 (blinded Placebo)
Ensifentrine is already approved in United States for the following indications:
🇺🇸 Approved in United States as Ohtuvayre for:
- Chronic obstructive pulmonary disease (COPD)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of MichiganAnn Arbor, MI
University of Alabama at BirminghamBirmingham, AL
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Who Is Running the Clinical Trial?
Verona Pharma plcLead Sponsor
University of Alabama at BirminghamCollaborator
References
Ensifentrine (RPL554): an inhaled 'bifunctional' dual PDE3/4 inhibitor for the treatment of asthma and chronic obstructive pulmonary disease. [2019]Ensifentrine (RPL554), an inhaled 'bifunctional' dual phosphodiesterase 3/4 inhibitor that exhibits both bronchodilator and anti-inflammatory activities, provides a new option in the treatment of chronic obstructive pulmonary disease (COPD) and other inflammatory airway diseases that are under clinical development. Ensifentrine appears to be initially under development for the treatment of COPD although it is not yet clear whether it should be understood as an add-on therapy in patients for the treatment of acute exacerbations of COPD or for the regular maintenance treatment of patients either alone, or on top of existing drug classes.
A Dose-Ranging Study of the Novel Inhaled Dual PDE 3 and 4 Inhibitor Ensifentrine in Patients with COPD Receiving Maintenance Tiotropium Therapy. [2023]Ensifentrine is an inhaled dual inhibitor of phosphodiesterase (PDE) 3 and 4 that has shown bronchodilatory effects and symptom improvement in clinical studies in patients with chronic obstructive pulmonary disease (COPD), and anti-inflammatory effects in healthy volunteers in a model of COPD-like inflammation. This manuscript reports on the results of the clinical study examining if ensifentrine provides meaningful improvements in lung function when added on to tiotropium over 4 weeks in patients with COPD who have impaired lung function and symptoms despite treatment with tiotropium.
Inhaled Dual Phosphodiesterase 3/4 Inhibitors for the Treatment of Patients with COPD: A Short Review. [2021]Current pharmacological treatments for chronic obstructive pulmonary disease (COPD) are mostly limited to inhaled bronchodilators and corticosteroids. Azithromycin can contribute to exacerbation prevention. Roflumilast, a phosphodiesterase (PDE) 4 inhibitor administered orally, also prevents exacerbations in selected patients with chronic bronchitis, recurrent exacerbations, severe airflow limitation and concomitant therapy with long-acting inhaled bronchodilators. This outcome likely results from anti-inflammatory effects since PDE4 is expressed by all inflammatory cell types involved in COPD. The use of this agent is, however, limited by side-effects, particularly nausea and diarrhea. To address remaining unmet needs and enrich therapeutic options for patients with COPD, inhaled dual PDE3/4 inhibitors have been developed, with the aim of enhancing bronchodilation through PDE3 inhibition and modulating inflammation and mucus production though PDE4 inhibition, thus producing a potentially synergistic effect on airway calibre. Experimental preclinical data confirmed these effects in vitro and in animal models. At present, RPL554/ensifentrine is the only agent of this family in clinical development. It decreases sputum markers of both neutrophilic and eosinophilic inflammation in patients with COPD. Clinical Phase II trials confirmed its bronchodilator effect and demonstrated clinically meaningful symptom relief and quality of life improvements in these patients. The safety profile appears satisfactory, with less effects on heart rate and blood pressure than salbutamol and no other side effect. Altogether, these data suggest that ensifentrine could have a role in COPD management, especially in addition to inhaled long-acting bronchodilators with or without corticosteroids since experimental studies suggest potentiation of ensifentrine effects by these agents. However, results from ongoing and future Phase III studies are needed to confirm both beneficial effects and favourable safety profile on a larger scale and assess other outcomes including exacerbations, lung function decline, comorbidities and mortality.
Ensifentrine, a Novel Phosphodiesterase 3 and 4 Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease: Randomized, Double-Blind, Placebo-controlled, Multicenter Phase III Trials (the ENHANCE Trials). [2023]Rationale: Ensifentrine is a novel, selective, dual phosphodiesterase (PDE)3 and PDE4 inhibitor with bronchodilator and antiinflammatory effects. Replicate phase III trials of nebulized ensifentrine were conducted (ENHANCE-1 and ENHANCE-2) to assess these effects in patients with chronic obstructive pulmonary disease (COPD). Objectives: To evaluate the efficacy of ensifentrine compared with placebo for lung function, symptoms, quality of life, and exacerbations in patients with COPD. Methods: These phase III, multicenter, randomized, double-blind, parallel-group, placebo-controlled trials were conducted between September 2020 and December 2022 at 250 research centers and pulmonology practices in 17 countries. Patients aged 40-80 years with moderate to severe symptomatic COPD were enrolled. Measurements and Main Results: Totals of 760 (ENHANCE-1) and 789 (ENHANCE-2) patients were randomized and treated, with 69% and 55% receiving concomitant long-acting muscarinic antagonists or long-acting β2-agonists, respectively. Post-bronchodilator FEV1 percentage predicted values were 52% and 51% of predicted normal. Ensifentrine treatment significantly improved average FEV1 area under the curve at 0-12 hours versus placebo (ENHANCE-1, 87 ml [95% confidence interval, 55, 119]; ENHANCE-2, 94 ml [65, 124]; both P < 0.001). Ensifentrine treatment significantly improved symptoms (Evaluating Respiratory Symptoms) and quality of life (St. George's Respiratory Questionnaire) versus placebo at Week 24 in ENHANCE-1 but not in ENHANCE-2. Ensifentrine treatment reduced the rate of moderate or severe exacerbations versus placebo over 24 weeks (ENHANCE-1, rate ratio, 0.64 [0.40, 1.00]; P = 0.050; ENHANCE-2, rate ratio, 0.57 [0.38, 0.87]; P = 0.009) and increased time to first exacerbation (ENHANCE-1, hazard ratio, 0.62 [0.39, 0.97]; P = 0.038; ENHANCE-2, hazard ratio, 0.58 [0.38, 0.87]; P = 0.009). Adverse event rates were similar to those for placebo. Conclusions: Ensifentrine significantly improved lung function in both trials, with results supporting exacerbation rate and risk reduction in a broad COPD population and in addition to other classes of maintenance therapies. Clinical trial registered with www.
Efficacy and safety of a first-in-class inhaled PDE3/4 inhibitor (ensifentrine) vs salbutamol in asthma. [2020]This study aimed to investigate the dose-response and pharmacology of a range of single doses of nebulised ensifentrine (RPL554), an inhaled dual phosphodiesterase (PDE) 3/4 inhibitor in patients with asthma.
The efficacy and safety of cilomilast in COPD. [2021]The aim of this review is to present the clinical data on the efficacy and safety of cilomilast in patients with chronic obstructive pulmonary disease (COPD). Over 6000 COPD patients received cilomilast during an extensive clinical development programme performed by GlaxoSmithKline (GSK).Five phase III randomized, double-blind, placebo-controlled, parallel-group pivotal studies were conducted in poorly reversible patients (
Effects of Roflumilast on Patients with Chronic Obstructive Pulmonary Disease Treated with Inhaled Corticosteroid/Long-Acting β2 Agonist: A Meta-analysis. [2022]Label="Objective" NlmCategory="UNASSIGNED">Roflumilast is a novel therapeutic drug for chronic obstructive pulmonary disease (COPD). This study was designed to evaluate the efficacy and safety of roflumilast combining inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) in treating COPD patients through the meta-analysis.
Ensifentrine as a Novel, Inhaled Treatment for Patients with COPD. [2023]Ensifentrine is a novel, potent, and selective dual inhibitor of phosphodiesterase (PDE)3 and PDE4 designed for delivery by inhalation that combines effects on airway inflammation, bronchodilation and ciliary function in bronchial epithelia. In Phase 2 studies in subjects with COPD, ensifentrine demonstrated clinically meaningful bronchodilation and improvements in symptoms and health-related quality of life when administered alone or in combination with current standard of care therapies. Ensifentrine is currently in late-stage clinical development for the maintenance treatment of patients with COPD. This review summarizes non-clinical data as well as Phase 1 and Phase 2 efficacy and safety results of nebulized ensifentrine relevant to the maintenance treatment of patients with COPD.