Ensifentrine for Bronchiectasis

Recruiting at19 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Verona Pharma plc

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

Disqualifiers: COPD, Asthma, Smoking, others

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This study is a randomized, double-blind, placebo-controlled study designed to assess the efficacy and safety of ensifentrine inhalation suspension (3 mg) delivered twice daily via standard jet nebulizer over at least 24 weeks, compared to placebo, in subjects with non-cystic fibrosis bronchiectasis (NCFBE).

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.

What data supports the effectiveness of the drug Ensifentrine for treating bronchiectasis?

Ensifentrine has shown effectiveness as a bronchodilator (helps open airways) and anti-inflammatory agent in treating asthma and chronic obstructive pulmonary disease (COPD), which are conditions involving airway inflammation similar to bronchiectasis. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Ensifentrine (Bronchodilator)

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.

Participant Groups

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

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

Who Is Running the Clinical Trial?

Verona Pharma plc

Lead Sponsor

Trials

16

Recruited

3,000+

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Ensifentrine (RPL554): an inhaled 'bifunctional' dual PDE3/4 inhibitor for the treatment of asthma and chronic obstructive pulmonary disease. [2019]

2. China pubmed.ncbi.nlm.nih.gov

Effect of OM-85 BV on reducing bronchiectasis exacerbation in Chinese patients: the iPROBE study. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a first-in-class inhaled PDE3/4 inhibitor (ensifentrine) vs salbutamol in asthma. [2020]

4. England 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. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Role of bromhexine in exacerbations of bronchiectasis. Double-blind randomized multicenter study versus placebo. [2018]