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

A Phase II, Randomized, Double-Blind, Placebo- Controlled Study of Ensifentrine in Subjects With Non-Cystic Fibrosis Bronchiectasis

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).

Study Overview

• Status: Recruiting
• Conditions: Non-cystic Fibrosis Bronchiectasis
• Intervention / Treatment: Drug: Nebulized Ensifentrine Suspension; 3 mg; Drug: Nebulized Placebo Solution

Detailed Description

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 Treatment Period for each subject will begin with the first dose of study medication and will continue for at least 24 weeks and up to 52 weeks. Subjects will end their Treatment Period at the Week 52 visit or when all active subjects in the study have completed through at least the Week 24 visit, whichever occurs first.

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.

• Study Type: Interventional
• Enrollment (Estimated): 284
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway Toll Free Number; Phone Number: 1-888-577-8839 Reach out by phone or email; Email: Trialsites@msd.com

Study Locations

• Italy
  • Bologna
    • Bologna, Bologna, Italy, 40138
      • Recruiting
      • IRCCS Azienda Ospedaliero-Universitaria di Bologna
  • Lombardi
    • Monza, Lombardi, Italy, 20900
      • Recruiting
      • Fondazione IRCCS San Gerardo dei Tintori
  • Lombardy
    • Rozzano, Lombardy, Italy, 20122
      • Recruiting
      • Istituto Clinico Humanitas
  • Pavia
    • Pavia, Pavia, Italy, 27100
      • Recruiting
      • Fondazione IRCCS Policlinico San Matteo
  • Sicily
    • Catania, Sicily, Italy, 95123
      • Recruiting
      • AOU Policlinico Gaspare Rodolico-San Marco Presidio Ospedaliero Gaspare Rodolico
• Spain
  • Madrid, Spain, 28223
    • Recruiting
    • Hospital Universitario Quironsalud Madrid
  • A Coruña
    • A Coruña, A Coruña, Spain, 15006
      • Recruiting
      • Hospital Universitario A Coruña
  • Barcelona
    • Barcelona, Barcelona, Spain, 08036
      • Recruiting
      • Hospital Clinic De Barcelona
    • Barcelona, Barcelona, Spain, 08003
      • Recruiting
      • Hospital del Mar
    • Barcelona, Barcelona, Spain, 08907
      • Recruiting
      • Hospital Universitario de Bellvitge
    • Barcelona, Barcelona, Spain, 08036
      • Recruiting
      • Hospital Universitario Vall d'Hebron - PPDS
  • Madrid
    • Madrid, Madrid, Spain, 28009
      • Recruiting
      • Hospital General Universitario Gregorio Marañón
    • Madrid, Madrid, Spain, 28046
      • Recruiting
      • Hospital Universitario La Paz - PPDS
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Recruiting
    • Queens Hospital Belfast
  • Cambridge, United Kingdom, CB2 0AY
    • Recruiting
    • Royal Papworth Hospital
  • Edinburgh, United Kingdom, EH16 4SA
    • Recruiting
    • Royal Infirmary of Edinburgh - PPDS
  • Liverpool, United Kingdom, L14 3PE
    • Recruiting
    • Liverpool Heart and Chest Hospital - PPDS
  • London, United Kingdom, SW3 6HP
    • Recruiting
    • Royal Brompton Hospital
  • Newcastle-under-Lyme, United Kingdom, NE7 7DN
    • Recruiting
    • Freeman Hospital
  • Dundee
    • Dundee, Dundee, United Kingdom, DD1 9SY
      • Recruiting
      • Ninewells Hospital - PPDS
  • Glasgow
    • Glasgow, Glasgow, United Kingdom, G12 0YN
      • Recruiting
      • Queen Elizabeth University Hospital - PPDS
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B9 5SS
      • Recruiting
      • Birmingham Heartlands Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • Kirklin Clinic of UAB Hospital
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • So Cal Institute for Respiratory Diseases, Inc.
    • Sacramento, California, United States, 95817
      • Recruiting
      • University of California Davis Medical Center
  • Colorado
    • Denver, Colorado, United States, 80206
      • Recruiting
      • National Jewish Health Main Campus
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Recruiting
      • MedStar Georgetown University Hospital
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Recruiting
      • Emory University at Saint Joseph Pulmonary Clinic
    • Augusta, Georgia, United States, 30912
      • Recruiting
      • Augusta University
  • Indiana
    • Hammond, Indiana, United States, 46324
      • Recruiting
      • ASHA Clinical Research
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • University of Kansas Medical Center-Kansas City
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital- 55 Fruit St
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health Pulmonary and Critical Care Associates, P.C. - BRANY - PPDS
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Recruiting
      • University of North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Terminated
      • Accellacare of Wilmington
    • Winston-Salem, North Carolina, United States, 27103
      • Recruiting
      • Southeastern Research Center
  • Ohio
    • Columbus, Ohio, United States, 43221
      • Recruiting
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Recruiting
      • Temple University Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina (MUSC) - PPDS
    • Spartanburg, South Carolina, United States, 29303
      • Recruiting
      • Velocity Clinical Research - Spartanburg - PPDS
    • Union, South Carolina, United States, 29379
      • Recruiting
      • Velocity Clinical Research - Union - PPDS
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Recruiting
      • Clinical Trials Center of Middle Tennessee
  • Texas
    • Houston, Texas, United States, 77094
      • Recruiting
      • The Respire Institute
    • Tyler, Texas, United States, 75708
      • Recruiting
      • UT Texas Health Science at Tyler
  • Virginia
    • Williamsburg, Virginia, United States, 23188
      • Recruiting
      • TPMG Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 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

Exclusion Criteria:

• 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

  1. 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
  2. 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
• A diagnosis of primary ciliary dyskinesia (PCD) is not exclusionary. Subjects with a diagnosis of PCD are permitted to be enrolled, but the proportion of subjects with PCD enrolled in the study may be limited
• 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. 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
  2. CFTR modulators (e.g., ivacaftor, lumacaftor, tezacaftor) within 1 week prior to signing the ICF
  3. Theophylline and oral PDE4 inhibitors (e.g., roflumilast, apremilast, crisaborole) within 48 hours prior to signing the ICF
  4. Ohtuvayre at any time prior to signing the ICF

• Initiated or altered therapy within 90 days prior to randomization with:

  1. oral or inhaled antibiotics as chronic treatment (including macrolides)
  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 through the day of randomization
  3. Dipeptidyl peptidase 1 (DPP1) or cathepsin C (CatC) inhibitor (e.g., brensocatib)
• 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 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, or 5 half-lives, whichever is longer, prior to signing the ICF
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm 1: Ensifentrine	Drug: 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 52 weeks
Placebo Comparator: Treatment Arm 2: Placebo	Drug: Nebulized Placebo Solution; Administered by a standard jet nebulizer, twice daily for a minimum of 24 weeks and up to a maximum of 52 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of protocol-defined pulmonary exacerbations (number of events per subject-year)	Through study completion (approximately 52 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK Sub-study only: Ensifentrine area under the curve from time 0 to 12 hours (AUC 0 -12)		Week 12, Week 18, and Week 24
PK Sub-study only: Ensifentrine maximum plasma drug concentration (Cmax)		Week 12, Week 18, and Week 24
Pharmacokinetic (PK) Sub-study only: Ensifentrine time to Cmax (tmax) post morning dose		Week 12, Week 18, and Week 24
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	The E-RS is a patient reported outcome that is derived from the EXAcerbation of Chronic Pulmonary Disease Tool (EXACT)-PRO in the participants e-diary, to quantify the severity of symptoms. The score ranges from 0 to 40 with a higher score representing more severe symptoms.	Baseline, Week 6, Week 12, and Week 24
Change from Baseline in Saint George's Respiratory Questionnaire (SGRQ) total score	SGRQ scores range from 0 to 100, with a higher score representing worse health.	Baseline, Week 6, Week 12, and Week 24
Change from Baseline in quality of life - bronchiectasis questionnaire (QOL-B) Respiratory Symptoms Domain score	The QOL-B Respiratory Symptoms Domain score ranges from 0 to 100, with higher scores representing better functioning.	Baseline, Week 6, Week 12, and Week 24
Change from Baseline in Chronic Airways Assessment Test (CAAT) total score	CAAT scores range from 0-40 with a higher score representing worse health.	Baseline, Week 6, Week 12, and Week 24
Change from Baseline in Percent of the predicted forced expiratory volume over 1 second (FEV1)		Baseline, Week 12, and Week 24
Change from Baseline of forced vital capacity (FVC)		Baseline, Week 12, and Week 24
Incidence of Adverse Events		Through study completion (approximately 52 weeks)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2024
• Primary Completion (Estimated): September 24, 2027
• Study Completion (Estimated): September 24, 2027

Study Registration Dates

• First Submitted: August 14, 2024
• First Submitted That Met QC Criteria: August 14, 2024
• First Posted (Actual): August 19, 2024

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Bronchial Diseases; Fibrosis; Bronchiectasis
• Other Study ID Numbers: RPL554-NCFB-220; 2024-514845-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No