Effect of Ensifentrine on Sputum Markers of Inflammation in COPD

NCT05270525 | Recruiting Phase 2 FDA Drug

• 1 other identifier: RPL554-CO-207
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

COPD

Outcome Measures

Primary Outcomes (1)

• The change from baseline in sputum neutrophils at Week 8 (absolute change in cell numbers)

  To measure the effect of nebulized ensifentrine on sputum absolute neutrophil count after twice daily dosing.

  Week 8

Secondary Outcomes (13)

• The change from baseline in sputum cell counts at Week 8 (absolute change in cell numbers)

  Week 8

• The percent change from baseline in sputum cell counts at Week 8

  Week 8

• The percent change from baseline in sputum markers of inflammation at Week 8

  Week 8

• The change from baseline in FEV1 after 4 weeks

  Week 4

• The change from baseline in FEV1 after 8 weeks (post-dose)

  Week 8

Other Outcomes (5)

• Exploratory: change from baseline in blood markers of inflammation after 4 weeks

  Week 4

• Exploratory: change from baseline in blood markers of inflammation after 8 weeks

  Week 8

• Exploratory: The percent change from baseline in sputum AcPGP at week 8

  Week 8

Study Arms (2)

Treatment Sequence 1

EXPERIMENTAL

Treatment Period 1 (blinded Ensifentrine) followed by Treatment Period 2 (blinded Placebo)

Drug: Ensifentrine; Drug: Placebo

Treatment Sequence 2

EXPERIMENTAL

Treatment Period 1 (blinded Placebo) followed by Treatment Period 2 (blinded Ensifentrine)

Drug: Ensifentrine; Drug: Placebo

Interventions

Ensifentrine DRUG

Ensifentrine twice daily administered with jet nebulizer for 8 weeks

Treatment Sequence 1; Treatment Sequence 2

Placebo DRUG

Placebo ensifentrine twice daily administered with jet nebulizer for 8 weeks

Treatment Sequence 1; Treatment Sequence 2

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients 40-80 years of age with a history of cigarette smoking ≥10 pack years and an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines with symptoms compatible with COPD.
• 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, LAMA+LABA+ICS), for at least 4 weeks prior to Screening and agrees to use study supplied COPD Maintenance Therapy once daily through the final study visit.
• Capable of using the jet nebulizer correctly and complying with all study restrictions and procedures. Ability to perform acceptable spirometry in accordance with ATS/ERS guidelines. Ability to produce sputum samples during the induced sputum procedure.

You may not qualify if:

• Any clinically diagnosed lung disease other than COPD such as current asthma, diffuse interstitial lung diseases, cystic fibrosis, or clinically significant bronchiectasis as determined by the Investigator. Hospitalizations for COPD, pneumonia, or Corona Virus Disease 2019 (COVID-19) in the 12 weeks prior to Screening; or a positive COVID-19 test result indicating an active infection at Screening.\*Note: Patients with a positive COVID-19 antibody test from a past exposure who do not exhibit symptoms of an active COVID-19 infection are eligible to participate in the study. \*A COVID-19 test may be performed at the visit or within 7 days prior to the visit (or as required locally). Asymptomatic patients with a positive COVID-19 test result indicating an active infection \< 30 days prior to Screening or at Screening may be re-screened for eligibility after 30 days (or in accordance with local requirements).
• 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.
• Any clinically significant 12-lead electrocardiogram abnormalities at screening or baseline, including corrected QT interval by Fridericia's correction method \>450 ms for males or \>480 ms for females or history of significant cardiac dysrhythmia, including long QT syndrome.
• Known history of poor outcomes with sputum induction. Known hypersensitivity to ensifentrine or other medications used in the study (e.g., albuterol or salmeterol). Not suitable for study supplied once daily COPD Maintenance Therapy per label warnings and contraindications.
• 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.

Sponsors & Collaborators

• Verona Pharma plc: lead
• University of Alabama at Birmingham: collaborator

Study Sites (3)

University of Alabama at Birmingham

Birmingham, Alabama, 35205, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

ensifentrine

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2022
• First Posted: March 8, 2022
• Study Start: May 27, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)