A Phase II Study of Ensifentrine in Non-Cystic Fibrosis Bronchiectasis

NCT ID: NCT06559150

Last Updated: 2025-10-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

180 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-11

Study Completion Date

2026-09-30

Brief Summary

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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).

Detailed Description

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The primary objective of this study is to assess the effect of ensifentrine vs placebo in addition to standard of care on pulmonary exacerbations, symptoms and quality of life in participants with NCFBE. The study is designed as a pulmonary exacerbation event-driven study where participants will be treated for ≥ 24 weeks and until at least 120 subjects have experienced at least 1 protocol-defined pulmonary exacerbation. Participants will be randomized to receive either ensifentrine suspension or placebo via standard jet nebulizer during the treatment period and neither participants nor study staff will know which a participant is receiving.

Conditions

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Non-cystic Fibrosis Bronchiectasis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Treatment Arm 1: Ensifentrine

Group Type EXPERIMENTAL

Nebulized Ensifentrine Suspension; 3 mg

Intervention Type DRUG

Administered by a standard jet nebulizer, twice daily for a minimum of 24 weeks and up to a maximum of 156 weeks (3 years)

Treatment Arm 2: Placebo

Group Type PLACEBO_COMPARATOR

Nebulized Placebo Solution

Intervention Type DRUG

Administered by a standard jet nebulizer, twice daily for a minimum of 24 weeks and up to a maximum of 156 weeks (3 years)

Interventions

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Nebulized Ensifentrine Suspension; 3 mg

Administered by a standard jet nebulizer, twice daily for a minimum of 24 weeks and up to a maximum of 156 weeks (3 years)

Intervention Type DRUG

Nebulized Placebo Solution

Administered by a standard jet nebulizer, twice daily for a minimum of 24 weeks and up to a maximum of 156 weeks (3 years)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Males are eligible to participate if they agree to use contraception as described in the contraceptive guidance from Screening and throughout the study and for at least 30 days after the last dose of blinded study medication
* Females are eligible to participate if they are not pregnant, not breastfeeding, and 1 of the following conditions apply:

1. Not a woman of childbearing potential (WOCBP) OR
2. A WOCBP who agrees to follow the contraceptive guidance from Screening throughout the study and for at least 30 days after the last dose of blinded study medication
* Clinical history consistent with bronchiectasis (cough, chronic sputum production, and/or recurrent respiratory infections) confirmed by chest CT demonstrating bronchiectasis affecting 1 or more lobes. Confirmation may be based on prior chest CT within the prior 5 years; subjects whose past CT image records are not available will require chest CT scan during screening Notes: If a subject has no clinical history consistent with bronchiectasis, they may not be re-screened
* Current sputum producer with a history of chronic expectoration and able to provide sputum sample spontaneously at the clinic during screening
* ≥ 1 documented pulmonary exacerbation defined by an antibiotic prescription by a physician for the signs and symptoms of respiratory infections in the past 12 months before screening
* Capable of using the study nebulizer correctly
* Ability to perform acceptable spirometry in accordance with American Thoracic Society and European Respiratory Society guidelines

Exclusion Criteria

* A diagnosis of COPD or a primary diagnosis of asthma, as judged by the investigator
* Bronchiectasis due to cystic fibrosis, hypogammaglobulinemia common variable immunodeficiency, severe immunodeficiency, or requirement for treatment with intravenous immunoglobulin
* Current smoker defined as by the Centers for Disease Control and Prevention (CDC)
* Former cigarette smokers with a history of cigarette smoking ≥ 10 pack years at Screening \[number of pack years = (number of cigarettes per day / 20) × number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)\]. Pipe and/or cigar use cannot be used to calculate pack-year history. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Screening
* A diagnosis of primary ciliary dyskinesia
* Current treatment for nontuberculous mycobacterial lung infection, allergic bronchopulmonary aspergillosis, or tuberculosis
* Presence of acute exacerbation or acute infection that required acute treatment within 28 days of randomization
* Use of the following prohibited medications within the designated time periods:

1. Immunomodulatory agents for any indication (including but not limited to the following: methotrexate, systemic corticosteroids, see adalimumab, azathioprine, dupilumab, cyclosporine) within 90 days prior to signing the ICF
2. CFTR modulators (e.g., ivacaftor, lumacaftor, tezacaftor) within 1 week prior to signing the ICF
3. Theophylline and PDE4 inhibitors (e.g., roflumilast, apremilast, crisaborole) within 48 hours prior to signing the ICF
4. Brensocatib within 3 months or 5 half-lives, whichever is longer, prior to signing the ICF
5. Ohtuvayre at any time prior to signing the ICF
* Initiated or altered therapy within 90 days of randomization with:

1. oral or inhaled antibiotics as chronic treatment
2. Cyclic antibiotics: defined as prescribed regular cycles of on antibiotic treatment and off antibiotic treatment (for example, but not limited to, 28 days on an antibiotic and 28 days off an antibiotic). Note: Subjects on cyclic antibiotics must be actively taking antibiotics for at least 7 days prior to randomization and through the day of randomization
* Initiated or altered therapy with ICS within 4 weeks prior to randomization
* Unable to withhold short-acting beta-agonists or short-acting muscarinic antagonists for ≥ 4 hours prior to spirometry
* Significant hemoptysis (≥ 300 mL or requiring blood transfusion) within 6 weeks prior to randomization
* Currently participating in or scheduled to participate in an intensive pulmonary rehabilitation program (a maintenance rehabilitation program is allowed if their schedule and procedure will be consistent for the duration of the study)
* Current or chronic history of unstable liver disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices or persistent jaundice, cirrhosis, or known hepatic or biliary abnormalities except for a diagnosis of Gilbert syndrome or asymptomatic gallstones Note: Chronic stable hepatitis B and C is not exclusionary if the subject otherwise meets study entry criteria
* History of or current malignancy of any organ system, treated or untreated within the past 5 years, except for localized basal or squamous cell carcinoma of the skin
* Estimated glomerular filtration rate (eGFR) \< 30 mL/min
* Alanine aminotransferase (ALT) ≥ 2 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≥ 2 × ULN, alkaline phosphatase and/or bilirubin \> 1.5 × ULN (isolated bilirubin \> 1.5 × ULN is acceptable only in subjects with a diagnosis of Gilbert's syndrome)
* Participation in any other interventional, clinical studies (drugs or devices) within 30 days before Day 1, or 5 half-lives, whichever is longer
* Intolerance of or hypersensitivity to ensifentrine or any of its excipients/components
* Current or history of drug or alcohol abuse within the past 5 years
* Significantly abnormal ECG finding
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Verona Pharma plc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Kirklin Clinic of UAB Hospital

Birmingham, Alabama, United States

Site Status RECRUITING

So Cal Institute for Respiratory Diseases, Inc.

Los Angeles, California, United States

Site Status RECRUITING

University of California Davis Medical Center

Sacramento, California, United States

Site Status RECRUITING

National Jewish Health Main Campus

Denver, Colorado, United States

Site Status RECRUITING

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status RECRUITING

University of Miami

Miami, Florida, United States

Site Status RECRUITING

Emory University at Saint Joseph Pulmonary Clinic

Atlanta, Georgia, United States

Site Status RECRUITING

Augusta University

Augusta, Georgia, United States

Site Status RECRUITING

ASHA Clinical Research

Hammond, Indiana, United States

Site Status RECRUITING

University of Iowa

Iowa City, Iowa, United States

Site Status RECRUITING

University of Kansas Medical Center-Kansas City

Kansas City, Kansas, United States

Site Status RECRUITING

Massachusetts General Hospital- 55 Fruit St

Boston, Massachusetts, United States

Site Status RECRUITING

University of Michigan Hospital

Ann Arbor, Michigan, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

NYU Langone Health Pulmonary and Critical Care Associates, P.C. - BRANY - PPDS

New York, New York, United States

Site Status RECRUITING

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Accellacare of Wilmington

Wilmington, North Carolina, United States

Site Status TERMINATED

Southeastern Research Center

Winston-Salem, North Carolina, United States

Site Status RECRUITING

Oregon Health and Science University

Portland, Oregon, United States

Site Status RECRUITING

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Medical University of South Carolina (MUSC) - PPDS

Charleston, South Carolina, United States

Site Status RECRUITING

Velocity Clinical Research - Spartanburg - PPDS

Spartanburg, South Carolina, United States

Site Status RECRUITING

Velocity Clinical Research - Union - PPDS

Union, South Carolina, United States

Site Status RECRUITING

Clinical Trials Center of Middle Tennessee

Franklin, Tennessee, United States

Site Status RECRUITING

The Respire Institute

Houston, Texas, United States

Site Status RECRUITING

UT Texas Health Science at Tyler

Tyler, Texas, United States

Site Status RECRUITING

TPMG Clinical Research

Williamsburg, Virginia, United States

Site Status RECRUITING

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Bologna, Bologna, Italy

Site Status RECRUITING

Fondazione IRCCS San Gerardo dei Tintori

Monza, Lombardi, Italy

Site Status RECRUITING

Istituto Clinico Humanitas

Rozzano, Lombardy, Italy

Site Status RECRUITING

Fondazione IRCCS Policlinico San Matteo

Pavia, Pavia, Italy

Site Status RECRUITING

AOU Policlinico Gaspare Rodolico-San Marco Presidio Ospedaliero Gaspare Rodolico

Catania, Sicily, Italy

Site Status RECRUITING

Hospital Universitario A Coruña

A Coruña, A Coruña, Spain

Site Status RECRUITING

Hospital del Mar

Barcelona, Barcelona, Spain

Site Status RECRUITING

Hospital Clinic de Barcelona

Barcelona, Barcelona, Spain

Site Status RECRUITING

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, Barcelona, Spain

Site Status RECRUITING

Hospital Universitario de Bellvitge

Barcelona, Barcelona, Spain

Site Status RECRUITING

Hospital General Universitario Gregorio Marañon

Madrid, Madrid, Spain

Site Status RECRUITING

Hospital Universitario La Paz - PPDS

Madrid, Madrid, Spain

Site Status RECRUITING

Hospital Universitario Quironsalud Madrid

Madrid, , Spain

Site Status RECRUITING

Ninewells Hospital - PPDS

Dundee, Dundee, United Kingdom

Site Status RECRUITING

Queen Elizabeth University Hospital - PPDS

Glasgow, Glasgow, United Kingdom

Site Status RECRUITING

Birmingham Heartlands Hospital

Birmingham, West Midlands, United Kingdom

Site Status RECRUITING

Queens Hospital Belfast

Belfast, , United Kingdom

Site Status RECRUITING

Royal Papworth Hospital

Cambridge, , United Kingdom

Site Status RECRUITING

Royal Infirmary of Edinburgh - PPDS

Edinburgh, , United Kingdom

Site Status RECRUITING

Liverpool Heart and Chest Hospital - PPDS

Liverpool, , United Kingdom

Site Status RECRUITING

Royal Brompton Hospital

London, , United Kingdom

Site Status RECRUITING

Freeman Hospital

Newcastle-under-Lyme, , United Kingdom

Site Status RECRUITING

Countries

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United States Italy Spain United Kingdom

Central Contacts

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Verona Pharma Clinical Trials

Role: CONTACT

Please reach out by email

Other Identifiers

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2024-514845-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RPL554-NCFB-220

Identifier Type: -

Identifier Source: org_study_id

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