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

NCT06559150 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: RPL554-NCFB-2202024-514845-12
• Study Type: interventional
• Target: 284
• Locations: 4 countries
• Sites: 51

Brief Summary

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).

Conditions

Non-cystic Fibrosis Bronchiectasis

Outcome Measures

Primary Outcomes (1)

• Rate of protocol-defined pulmonary exacerbations (number of events per subject-year)

  Through study completion (approximately 52 weeks)

Secondary Outcomes (11)

• Time to the onset of the first protocol-defined pulmonary exacerbation

  Through study completion (approximately 52 weeks)

• Change from Baseline in Evaluating Respiratory Symptoms (E-RS) Cough and Sputum Domain score

  Baseline, Week 6, Week 12, and Week 24

• Change from Baseline in Saint George's Respiratory Questionnaire (SGRQ) total score

  Baseline, Week 6, Week 12, and Week 24

• Change from Baseline in quality of life - bronchiectasis questionnaire (QOL-B) Respiratory Symptoms Domain score

  Baseline, Week 6, Week 12, and Week 24

• Change from Baseline in Chronic Airways Assessment Test (CAAT) total score

  Baseline, Week 6, Week 12, and Week 24

Study Arms (2)

Treatment Arm 1: Ensifentrine

EXPERIMENTAL

Drug: Nebulized Ensifentrine Suspension; 3 mg

Treatment Arm 2: Placebo

PLACEBO COMPARATOR

Drug: Nebulized Placebo Solution

Interventions

Nebulized Ensifentrine Suspension; 3 mg DRUG

Administered by a standard jet nebulizer, twice daily for a minimum of 24 weeks and up to a maximum of 52 weeks

Treatment Arm 1: Ensifentrine

Nebulized Placebo Solution DRUG

Administered by a standard jet nebulizer, twice daily for a minimum of 24 weeks and up to a maximum of 52 weeks

Treatment Arm 2: Placebo

Eligibility Criteria

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

You may qualify if:

• 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:
• Not a woman of childbearing potential (WOCBP) OR
• 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 antimicrobial prescription (i.e., antibiotic or antiviral) 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 as assessed by the Investigator

You may not qualify if:

• A diagnosis of COPD or a primary diagnosis of asthma, as judged by the investigator
• Bronchiectasis due to cystic fibrosis, primary 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)
• Meets both of the following
• 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 AND
• Evidence within 1 year prior to randomization of obstructed lung function as shown by forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio of \< 0.70
• 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:
• Chronic, systemic immunomodulatory agents for any chronic indication (including but not limited to the following: methotrexate, systemic corticosteroids, see adalimumab, azathioprine, dupilumab, cyclosporine, hydroxychloroquine, etc.) within 90 days prior to signing the ICF
• CFTR modulators (e.g., ivacaftor, lumacaftor, tezacaftor) within 1 week prior to signing the ICF
• Theophylline and oral PDE4 inhibitors (e.g., roflumilast, apremilast, crisaborole) within 48 hours prior to signing the ICF
• Ohtuvayre at any time prior to signing the ICF
• Initiated or altered therapy within 90 days prior to randomization with:
• oral or inhaled antibiotics as chronic treatment (including macrolides)

Sponsors & Collaborators

• Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA: lead

Study Sites (51)

Kirklin Clinic of UAB Hospital

Birmingham, Alabama, 35233, United States

RECRUITING

So Cal Institute for Respiratory Diseases, Inc.

Los Angeles, California, 90048, United States

RECRUITING

University of California Davis Medical Center

Sacramento, California, 95817, United States

RECRUITING

National Jewish Health Main Campus

Denver, Colorado, 80206, United States

RECRUITING

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

RECRUITING

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Emory University at Saint Joseph Pulmonary Clinic

Atlanta, Georgia, 30342, United States

RECRUITING

Augusta University

Augusta, Georgia, 30912, United States

RECRUITING

ASHA Clinical Research

Hammond, Indiana, 46324, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

University of Kansas Medical Center-Kansas City

Kansas City, Kansas, 66160, United States

RECRUITING

Massachusetts General Hospital- 55 Fruit St

Boston, Massachusetts, 02114, United States

RECRUITING

University of Michigan Hospital

Ann Arbor, Michigan, 48109, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

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

New York, New York, 10016, United States

RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

RECRUITING

Accellacare of Wilmington

Wilmington, North Carolina, 28401, United States

TERMINATED

Southeastern Research Center

Winston-Salem, North Carolina, 27103, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43221, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

RECRUITING

Medical University of South Carolina (MUSC) - PPDS

Charleston, South Carolina, 29425, United States

RECRUITING

Velocity Clinical Research - Spartanburg - PPDS

Spartanburg, South Carolina, 29303, United States

RECRUITING

Velocity Clinical Research - Union - PPDS

Union, South Carolina, 29379, United States

RECRUITING

Clinical Trials Center of Middle Tennessee

Franklin, Tennessee, 37067, United States

RECRUITING

The Respire Institute

Houston, Texas, 77094, United States

RECRUITING

UT Texas Health Science at Tyler

Tyler, Texas, 75708, United States

RECRUITING

TPMG Clinical Research

Williamsburg, Virginia, 23188, United States

RECRUITING

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Bologna, Bologna, 40138, Italy

RECRUITING

Fondazione IRCCS San Gerardo dei Tintori

Monza, Lombardi, 20900, Italy

RECRUITING

Istituto Clinico Humanitas

Rozzano, Lombardy, 20122, Italy

RECRUITING

Fondazione IRCCS Policlinico San Matteo

Pavia, Pavia, 27100, Italy

RECRUITING

AOU Policlinico Gaspare Rodolico-San Marco Presidio Ospedaliero Gaspare Rodolico

Catania, Sicily, 95123, Italy

RECRUITING

Hospital Universitario A Coruña

A Coruña, A Coruña, 15006, Spain

RECRUITING

Hospital del Mar

Barcelona, Barcelona, 08003, Spain

RECRUITING

Hospital Clinic de Barcelona

Barcelona, Barcelona, 08036, Spain

RECRUITING

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, Barcelona, 08036, Spain

RECRUITING

Hospital Universitario de Bellvitge

Barcelona, Barcelona, 08907, Spain

RECRUITING

Hospital General Universitario Gregorio Marañon

Madrid, Madrid, 28009, Spain

RECRUITING

Hospital Universitario La Paz - PPDS

Madrid, Madrid, 28046, Spain

RECRUITING

Hospital Universitario Quironsalud Madrid

Madrid, 28223, Spain

RECRUITING

Ninewells Hospital - PPDS

Dundee, Dundee, DD1 9SY, United Kingdom

RECRUITING

Queen Elizabeth University Hospital - PPDS

Glasgow, Glasgow, G12 0YN, United Kingdom

RECRUITING

Birmingham Heartlands Hospital

Birmingham, West Midlands, B9 5SS, United Kingdom

RECRUITING

Queens Hospital Belfast

Belfast, BT9 7AB, United Kingdom

RECRUITING

Royal Papworth Hospital

Cambridge, CB2 0AY, United Kingdom

RECRUITING

Royal Infirmary of Edinburgh - PPDS

Edinburgh, EH16 4SA, United Kingdom

RECRUITING

Liverpool Heart and Chest Hospital - PPDS

Liverpool, L14 3PE, United Kingdom

RECRUITING

Royal Brompton Hospital

London, SW3 6HP, United Kingdom

RECRUITING

Freeman Hospital

Newcastle-under-Lyme, NE7 7DN, United Kingdom

RECRUITING

Central Study Contacts

Verona Pharma Clinical Trials

CONTACT

Please reach out by email; clinicaltrials@veronapharma.com

Study Design

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

Study Record Dates

• First Submitted: August 14, 2024
• First Posted: August 19, 2024
• Study Start: September 11, 2024
• Primary Completion (Estimated): September 24, 2027
• Study Completion (Estimated): September 24, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (8); GB (9); US (29); IT (5)