Ensifentrine for Bronchiectasis

Recruiting at 51 trial locations

Overseen By Verona Pharma Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Verona Pharma plc

Must not be taking: Immunomodulators, CFTR modulators, PDE4 inhibitors, others

Disqualifiers: COPD, Asthma, Smoking, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: ≥ 24 weeks

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new inhalation treatment called ensifentrine to determine its effectiveness for individuals with non-cystic fibrosis bronchiectasis, a lung condition that causes coughing and mucus buildup. The goal is to assess whether ensifentrine can improve symptoms and ensure its safety over 24 weeks. Participants will receive either the ensifentrine treatment or a placebo (a harmless substance with no therapeutic effect) to compare results. This study suits those with a history of bronchiectasis, symptoms like chronic coughing and mucus production, and who have required antibiotics for lung infections in the past year. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial requires stopping certain medications before joining. You must stop using immunomodulatory agents 3 months prior, CFTR modulators 1 week prior, cyclic antibiotics 90 days prior, theophylline and PDE4 inhibitors 48 hours prior, and brensocatib 3 months or 5 half-lives prior. Other medications may also need to be stopped or adjusted, so it's best to discuss with the trial team.

Is there any evidence suggesting that ensifentrine is likely to be safe for humans?

Research shows that ensifentrine is generally safe. Studies have found that it improves lung function in people with Chronic Obstructive Pulmonary Disease (COPD). Most participants in these studies tolerated ensifentrine well, experiencing no serious side effects. The most common side effects were mild, such as back pain.

Evidence for ensifentrine's safety comes from its use in other breathing conditions, like COPD, indicating it has been tested and deemed safe for these patients. However, individual experiences can vary. Discuss potential risks with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ensifentrine is unique because it combines bronchodilator and anti-inflammatory effects in a single treatment, which is not common among current options for bronchiectasis. Most treatments for this condition, like antibiotics and mucolytics, focus on managing symptoms or treating infections rather than addressing the underlying inflammation and airway constriction. Ensifentrine works differently by inhibiting enzymes called phosphodiesterases, which helps relax the airway muscles and reduces inflammation. Researchers are excited about Ensifentrine because it has the potential to improve lung function and reduce the frequency of exacerbations, offering a more comprehensive approach to managing bronchiectasis.

What evidence suggests that ensifentrine might be an effective treatment for non-cystic fibrosis bronchiectasis?

Research shows that ensifentrine, which participants in this trial may receive, acts effectively as a bronchodilator, opening up the airways. This benefits people with asthma and chronic obstructive pulmonary disease (COPD). In studies, patients using ensifentrine experienced better lung function and improved quality of life. Its anti-inflammatory properties also help reduce airway swelling. Importantly, these benefits come with few side effects, making it a promising treatment for those with breathing problems. While this study focuses on non-cystic fibrosis bronchiectasis, its previous success in similar lung conditions suggests potential effectiveness. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with non-cystic fibrosis bronchiectasis who produce sputum, have had at least one lung infection in the past year, and can use a nebulizer correctly. Women must agree to follow contraceptive guidance if of childbearing potential. Those without a history or CT scan evidence of bronchiectasis are excluded.

Inclusion Criteria

I can use the study's nebulizer correctly.

My chest CT shows I have bronchiectasis.

I can successfully complete a lung function test.

Exclusion Criteria

I have not had any cancer except for certain types in the last 5 years.

I have been diagnosed with primary ciliary dyskinesia.

Current or history of drug or alcohol abuse within the past 5 years

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ensifentrine or placebo via nebulizer for at least 24 weeks

≥ 24 weeks

Visits at Baseline, Week 6, Week 12, and Week 24

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ensifentrine

Trial Overview The study tests Ensifentrine inhalation suspension (3 mg) against a placebo solution, both delivered twice daily via nebulizer over 24 weeks. It's randomized and double-blind, meaning participants and researchers don't know who gets the real treatment or placebo.

How Is the Trial Designed?

Group I: Treatment Arm 1: Ensifentrine Experimental Treatment 1 Intervention

Group II: Treatment Arm 2: Placebo Placebo Group 1 Intervention

Ensifentrine is already approved in United States for the following indications:

Approved in United States as Ohtuvayre for:

• Chronic obstructive pulmonary disease (COPD)

Who Is Running the Clinical Trial?

Verona Pharma plc

Lead Sponsor

Trials

16

Recruited

3,000+

Published Research Related to This Trial

Ensifentrine (RPL554) is an inhaled medication that acts as a dual inhibitor of phosphodiesterase 3 and 4, providing both bronchodilation and anti-inflammatory effects, making it a promising treatment for chronic obstructive pulmonary disease (COPD).

Currently under clinical development, it is uncertain whether ensifentrine will serve as an add-on therapy for acute COPD exacerbations or as a standalone maintenance treatment, indicating the need for further research to clarify its optimal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ensifentrine (RPL554): an inhaled 'bifunctional' dual PDE3/4 inhibitor for the treatment of asthma and chronic obstructive pulmonary disease. Cazzola, M., Page, C., Calzetta, L., et al.[2019]

In a 1-year study involving 196 patients with bronchiectasis, OM-85 BV did not significantly reduce the number of acute exacerbations compared to placebo, indicating it may not be effective for preventing exacerbations in this population.

The safety profile of OM-85 BV was good, with most adverse events being mild, suggesting it is safe for use even though it did not show efficacy in reducing exacerbations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of OM-85 BV on reducing bronchiectasis exacerbation in Chinese patients: the iPROBE study. Gao, J., Li, L., Jiang, N., et al.[2022]

Nebulised ensifentrine showed a clear dose-response relationship in improving lung function (FEV1) in asthma patients, outperforming placebo and demonstrating effectiveness comparable to salbutamol, a standard asthma treatment.

All doses of ensifentrine were well tolerated with no significant adverse effects on heart rate or potassium levels, unlike salbutamol, which caused dose-related reductions in potassium and increased heart rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a first-in-class inhaled PDE3/4 inhibitor (ensifentrine) vs salbutamol in asthma. Bjermer, L., Abbott-Banner, K., Newman, K.[2020]

In the ORBIT-4 trial, inhaled liposomal ciprofloxacin (ARD-3150) significantly increased the median time to the first pulmonary exacerbation in patients with non-cystic fibrosis bronchiectasis compared to placebo, with a difference of 72 days (230 days vs. 158 days).

The safety profile of ARD-3150 was comparable to placebo, with similar rates of adverse events in both treatment groups across the trials, indicating that it is a safe option for patients with chronic Pseudomonas aeruginosa lung infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled liposomal ciprofloxacin in patients with non-cystic fibrosis bronchiectasis and chronic lung infection with Pseudomonas aeruginosa (ORBIT-3 and ORBIT-4): two phase 3, randomised controlled trials. Haworth, CS., Bilton, D., Chalmers, JD., et al.[2020]

In a double-blind, placebo-controlled trial with 88 patients suffering from bronchiectasis, bromhexine showed significant improvements in expectoration, sputum quantity, and lung function (FEV1), indicating its efficacy during clinical exacerbations.

Bromhexine was well-tolerated by patients, and both patients and investigators reported it as an effective treatment, suggesting it could be a beneficial addition to standard care for bronchiectasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of bromhexine in exacerbations of bronchiectasis. Double-blind randomized multicenter study versus placebo. Olivieri, D., Ciaccia, A., Marangio, E., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12181703/

Efficacy and safety of ensifentrine in treatment of COPD Ensifentrine has a significant impact on improving pulmonary function and quality of life with minimal side effects.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2949789225000777

Lung Function and Safety Outcomes in Patients With ... With respect to COPD severity, 57.5% and 53.5% of patients in the ensifentrine and placebo groups were classified as having moderate COPD, ...

3. withpower.com withpower.com/trial/phase-2-non-cystic-fibrosis-bronchiectasis-8-2024-a96f8

Ensifentrine for Bronchiectasis Ensifentrine has shown effectiveness as a bronchodilator (helps open airways) and anti-inflammatory agent in treating asthma and chronic obstructive pulmonary ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT07016412

A Phase IIb Ensifentrine-glycopyrrolate Fixed-dose ... This study will assess the safety and efficacy of fixed dose combinations of ensifentrine with two different glycopyrrolate dose levels compared to placebo ...

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2024/217389Orig1s000IntegratedR.pdf

217389Orig1s000 INTEGRATED REVIEW - accessdata.fda.gov Similar to the results of Trial 301, the bronchodilatory effect of ensifentrine ... ensifentrine PK incorporating data from phase 3 study RPL554- ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05743075

A Study to Evaluate the Efficacy and Safety of Ensifentrine ... 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 ...

7. icer.org icer.org/wp-content/uploads/2024/04/COPD_Draft-Report_For-Publication_04102024.pdf

Ensifentrine for the Treatment of Chronic Obstructive ... We sought and reviewed evidence on patient-important outcomes (e.g., changes in COPD exacerbations, respiratory symptoms, quality of life, etc.) ...