A Phase IIb Ensifentrine-glycopyrrolate Fixed-dose Combination Dose Ranging Study in Subjects With COPD

NCT07016412 | Recruiting Phase 2 FDA Drug

• 1 other identifier: RPL554-CO-212
• Study Type: interventional
• Target: 480
• Locations: 1 country
• Sites: 55

Brief Summary

This study will assess the safety and efficacy of fixed dose combinations of ensifentrine with two different glycopyrrolate dose levels compared to placebo and to the individual components of the fixed dose combinations, each administered twice a day via standard jet nebulizer, in adult subjects with chronic obstructive pulmonary disease (COPD).

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

Chronic Obstructive Pulmonary Disease; COPD; bronchodilator; ensifentrine-glycopyrrolate

Outcome Measures

Primary Outcomes (1)

• Change from baseline in average forced expiry volume in 1 second (FEV1) area under the curve versus time, from time 0 to 4 hours (AUC0-4h)

  Baseline and Days 1, 14, 28, and 29

Secondary Outcomes (12)

• Change from baseline in peak FEV1 measured over 4 hours post-dose

  Baseline and Day 28

• Change from baseline in average FEV1 area under the curve versus time, from time 0 to 12 hours (AUC0-12h)

  Baseline and Day 28

• Change from baseline in morning trough FEV1 on Day 29

  Baseline and Day 29

• Change from baseline in evening trough FEV1 on Day 28

  Baseline and Day 28

• Change from baseline in morning trough FEV1 on Day 28

  Baseline and Day 28

Study Arms (6)

Treatment Arm A: Ensifentrine plus Glycopyrrolate

EXPERIMENTAL

Ensifentrine 3 mg / Glycopyrrolate 42.5 mcg

Drug: Ensifentrine 3 mg; Drug: Glycopyrrolate 42.5 mcg

Treatment Arm B: Ensifentrine plus Glycopyrrolate

EXPERIMENTAL

Ensifentrine 3 mg / Glycopyrrolate 21.25 mcg

Drug: Ensifentrine 3 mg; Drug: Glycopyrrolate 21.25 mcg

Treatment Arm C: Glycopyrrolate

ACTIVE COMPARATOR

Glycopyrrolate monotherapy 42.5 mcg

Drug: Glycopyrrolate 42.5 mcg

Treatment Arm D: Glycopyrrolate

ACTIVE COMPARATOR

Glycopyrrolate monotherapy 21.25 mcg

Drug: Glycopyrrolate 21.25 mcg

Treatment Arm E: Ensifentrine

ACTIVE COMPARATOR

Ensifentrine monotherapy 3 mg

Drug: Ensifentrine 3 mg

Treatment Arm F: Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Glycopyrrolate 42.5 mcg DRUG

Administered by a standard jet nebulizer, twice daily for 28 consecutive days

Treatment Arm A: Ensifentrine plus Glycopyrrolate; Treatment Arm C: Glycopyrrolate

Placebo DRUG

Administered by a standard jet nebulizer, twice daily for 28 consecutive days

Treatment Arm F: Placebo

Glycopyrrolate 21.25 mcg DRUG

Administered by a standard jet nebulizer, twice daily for 28 consecutive days

Treatment Arm B: Ensifentrine plus Glycopyrrolate; Treatment Arm D: Glycopyrrolate

Ensifentrine 3 mg DRUG

Administered by a standard jet nebulizer, twice daily for 28 consecutive days

Treatment Arm A: Ensifentrine plus Glycopyrrolate; Treatment Arm B: Ensifentrine plus Glycopyrrolate; Treatment Arm E: Ensifentrine

Eligibility Criteria

• Age: 40 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 or abstinence, and refrain from donating fresh unwashed semen during the study and for at least 30 days post-study
• Females are eligible to participate if they are not pregnant, breastfeeding and if one of the following conditions apply:
• Not a woman of child-bearing potential OR
• Agrees to follow the contraceptive guidance from screening throughout the study and for at least 30 days post-study
• Agrees not to donate eggs for the purpose of reproduction from screening throughout the study and for at least 30 days post-study
• Current of former cigarette smokers with a history of smoking ≥ 10 pack years at the time of signing informed consent \[number of pack years = (number of cigarettes per day / 20) × number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)\]. 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 signing informed consent. Smoking cessation programs are permitted during the study
• Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines with symptoms compatible with COPD
• A score of ≥ 2 on the Modified Medical Research Council (mMRC) Dyspnea Scale at the Screening Visit
• Post-bronchodilator (4 puffs of albuterol) spirometry during the Screening Period demonstrating both the following:
• FEV1/forced vital capacity (FVC) ratio of \< 0.70 AND
• FEV1 ≥ 30 % and ≤ 70% of predicted normal
• A posterior-anterior chest x-ray (CXR) during the Screening Period or within 12 months of signing the Informed Consent Form (ICF) showing no clinically significant abnormalities unrelated to COPD. If a CXR within the past 12 months is not available but a computed tomography (CT) scan within the same time period is available, the CT scan may be reviewed in place of a CXR
• Subjects on no maintenance/background therapy or subjects on stable maintenance as either long-acting β2-agonist (LABA) or long-acting β2-agonist/Inhaled corticosteroid (LABA/ICS) therapy are eligible. Subjects taking maintenance therapy must demonstrate regular use of maintenance therapy, in any form, for at least 60 days prior to signing informed consent and agree to continue use of their current permitted LABA or LABA/ICS medication for the duration of the screening and treatment period
• Capable of withholding from short-acting bronchodilators for 4 hours prior to spirometry testing. Subjects receiving maintenance therapy with a LABA or LABA/ICS must be capable of withholding twice-daily maintenance therapy for 24 hours and once-daily maintenance therapy for 48 hours prior to initiation of any spirometry
• Capable of using the study jet nebulizer correctly

You may not qualify if:

• Concomitant clinically significant pulmonary disease other than COPD (i.e., asthma, tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, sleep apnea (unless controlled with stable continuous positive airway pressure \[CPAP\] use), known alpha-1 antitrypsin deficiency, core pulmonale or other non-specific pulmonary disease
• Within 6 months prior to randomization, a COPD exacerbation requiring hospitalization
• Within 3 months prior to randomization, use of oral or systemic therapies for COPD exacerbations (for example, oral, intravenous, or intramuscular glucocorticoids, antibiotics, theophylline, and roflumilast)
• History of life-threatening COPD, including Intensive Care Unit admission and/or requiring intubation
• Severe comorbidities including
• unstable cardiac disease (myocardial infarction within 1 year prior to randomization, unstable angina within 6 months prior to randomization, unstable or life-threatening arrhythmia requiring intervention within 3 months prior to randomization, diagnosis of New York Heart Association (NYHA) class III or IV heart disease, or
• any other clinically significant medical conditions including uncontrolled diseases (e.g., endocrine, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, psychiatric \[e.g. untreated significant depression, anxiety or history of suicidality\], or ophthalmic diseases) that would, in the opinion of the Investigator, preclude the subject from safely completing the required tests or the study, or is likely to result in disease progression that would require withdrawal of the subject
• History of or clinically significant on-going bladder outflow obstruction or history of catheterization for relief of bladder outflow obstruction within 6 months prior to randomization
• History of narrow angle glaucoma
• History of hypersensitivity or intolerance to aerosol medications, albuterol, ensifentrine, or glycopyrrolate or any of its excipients/components, anticholinergic agents, or sympathomimetic amines
• History of or current malignancy of any organ system, treated or untreated within the 5 years prior to randomization, except for localized basal or squamous cell carcinoma of the skin
• Other significant psychiatric disease that would likely result in the subject not being able to complete the study, in the opinion of the Investigator
• Findings on physical examination that an investigator considers to be clinically significant or abnormal during the Screening Period including hematology, biochemistry, viral serology, and ECG
• Prior or current use of Ohtuvayre (ensifentrine)
• Previous lung resection or lung reduction surgery within 1-year of randomization

Sponsors & Collaborators

• Verona Pharma plc: lead

Study Sites (55)

SEC Clinical Research, LLC

Dothan, Alabama, 36305-7375, United States

RECRUITING

Elite Clinical Studies, LLC

Phoenix, Arizona, 85018, United States

RECRUITING

Downtown LA Research Center Inc - ClinEdge

Los Angeles, California, 90017, United States

RECRUITING

California Medical Research Associates, Inc.

Northridge, California, 91324-6200, United States

RECRUITING

Northern California Research Corp

Sacramento, California, 95821-2640, United States

RECRUITING

Clinical Research of West Florida Inc

Clearwater, Florida, 33765, United States

RECRUITING

Fleming Island Center For Clinical Research

Fleming Island, Florida, 32003, United States

RECRUITING

Florida Institute For Clinical Research LLC

Orlando, Florida, 32825-4454, United States

RECRUITING

Ormond Beach Clinical Research

Ormond Beach, Florida, 32174-8196, United States

RECRUITING

Progressive Medical Research

Port Orange, Florida, 32127-5169, United States

RECRUITING

Clinical Research of West Florida Inc - Tampa

Tampa, Florida, 33606, United States

RECRUITING

Centricity Research Columbus Georgia Multispecialty - PPDS

Columbus, Georgia, 31904, United States

RECRUITING

Southeast Lung Associates Research

Rincon, Georgia, 31326, United States

WITHDRAWN

ASHA Clinical Research - Hammond

Hammond, Indiana, 46324, United States

RECRUITING

Velocity Clinical Research - Valparaiso

Valparaiso, Indiana, 46383, United States

RECRUITING

Velocity Clinical Research (Rockville - Maryland) - PPDS

Rockville, Maryland, 20854-2960, United States

RECRUITING

Revive Research Institute, Inc

Southfield, Michigan, 48075, United States

RECRUITING

Midwest Chest Consultants PC

Saint Charles, Missouri, 63301, United States

RECRUITING

Midwest Clinical Research LLC

St Louis, Missouri, 63141-7051, United States

RECRUITING

The Clinical Research Center LLC - CRN

St Louis, Missouri, 63141, United States

RECRUITING

Sierra Clinical Research

Las Vegas, Nevada, 89106, United States

TERMINATED

Trialfinity Clinical Research Center

Hamilton, New Jersey, 08619, United States

RECRUITING

Horizon Family Medical Group - New Windsor Primary Care

New Windsor, New York, 12553-7754, United States

RECRUITING

American Health Research Inc

Charlotte, North Carolina, 28277, United States

RECRUITING

Clinical Research of Gastonia

Gastonia, North Carolina, 28054-7481, United States

RECRUITING

Stern Research Partners, LLC

Huntersville, North Carolina, 28078, United States

RECRUITING

Monroe Biomedical Research -343 Venus St

Monroe, North Carolina, 28112-4025, United States

RECRUITING

Carolina Research Center, Inc

Shelby, North Carolina, 28150-3803, United States

RECRUITING

Remington Davis Clinical Research

Columbus, Ohio, 43215, United States

RECRUITING

Advance Clinical Research

Kettering, Ohio, 45439, United States

RECRUITING

Clinical Research Associates of Central PA

DuBois, Pennsylvania, 15801-2277, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Velocity Clinical Research - Anderson - PPDS

Anderson, South Carolina, 29621-4822, United States

RECRUITING

Pharmacorp Clinical Trials Incorporated

Charleston, South Carolina, 29412, United States

RECRUITING

Piedmont Research Partners LLC

Fort Mill, South Carolina, 29707-4514, United States

RECRUITING

Velocity Clinical Research - Gaffney - PPDS

Gaffney, South Carolina, 29340-4737, United States

RECRUITING

Lowcountry Lung and Critical Care PA

North Charleston, South Carolina, 29406, United States

RECRUITING

Monroe Biomedical Research Charleston

North Charleston, South Carolina, 29406, United States

RECRUITING

Clinical Research of Rock Hill

Rock Hill, South Carolina, 29732, United States

RECRUITING

Spartanburg Medical Research

Spartanburg, South Carolina, 29303-4755, United States

RECRUITING

Velocity Clinical Research

Spartanburg, South Carolina, 29303, United States

RECRUITING

Velocity Clinical Research - Union - PPDS

Union, South Carolina, 29379, United States

RECRUITING

Chattanooga Research & Medicine, PLLC

Chattanooga, Tennessee, 37404, United States

RECRUITING

ClinSearch - Chattanooga

Chattanooga, Tennessee, 37421, United States

RECRUITING

Clinical Trials Center of Middle Tennessee

Franklin, Tennessee, 37067-5665, United States

RECRUITING

MultiSpecialty Clinical Research, Inc

Johnson City, Tennessee, 37604, United States

RECRUITING

Inquest Clinical Research

Baytown, Texas, 77521, United States

RECRUITING

Corsicana Medical Research

Corsicana, Texas, 75110-2471, United States

RECRUITING

Horizon CR: Houston Pulmonary Sleep & Allergy Associates - Cypress - ClinEdge - PPDS

Cypress, Texas, 77429, United States

RECRUITING

Greater Heights Memorial Pulmonary and Sleep

Houston, Texas, 77008, United States

RECRUITING

Houston Pulmonary Medicine Associates, PA - Biopharma Informatic - PPDS

Houston, Texas, 77089, United States

RECRUITING

Huntsville Research Institute LLC

Huntsville, Texas, 77340, United States

RECRUITING

Element Research Group

San Antonio, Texas, 78258, United States

RECRUITING

Sherman Clinical Research - 403 N. Highland Ave

Sherman, Texas, 75092, United States

RECRUITING

Tranquil Clinical Research

Webster, Texas, 77598-4085, United States

RECRUITING

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

ensifentrine; Glycopyrrolate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

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

Study Record Dates

• First Submitted: June 3, 2025
• First Posted: June 11, 2025
• Study Start: July 31, 2025
• Primary Completion (Estimated): July 29, 2026
• Study Completion (Estimated): July 29, 2026
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (55)