Effect of Ensifentrine (MK-5884/RPL554) on Sputum Markers of Inflammation in Chronic Obstructive Pulmonary Disease (COPD) (MK-5884-023/RPL554-CO-207)

October 29, 2026 updated by: Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA

A Randomized, Double-Blind, Placebo-Controlled, Two-period Cross-over Study of the Effect of Ensifentrine on Sputum Markers of Inflammation in Subjects With COPD

Researchers are looking for new ways to treat chronic obstructive pulmonary disease (COPD). COPD is a long-lasting swelling of the airways that makes it hard to breathe. Researchers want to learn if a trial medicine called ensifentrine can help treat sputum caused by COPD. In this trial, researchers will compare a trial medicine called ensifentrine to a placebo. A placebo looks like the trial medicine but has no medicine in it. Using a placebo helps researchers better understand the effects of a trial medicine.

The goal of this trial is to learn about the effect of ensifentrine on a substance found in mucus (sputum) from the lungs that may be a sign of inflammation in participants with COPD.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
70

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35205
        • University of Alabama at Birmingham
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Participants with a history of cigarette smoking ≥10 pack years and an established clinical history of chronic obstructive pulmonary disease (COPD) as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines with symptoms compatible with COPD. 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]
  • COPD Severity: Pre- and Post-albuterol/salbutamol Forced expiratory volume in 1 second/Forced vital capacity (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., [Long-acting muscarinic antagonist] LAMA, [Long-acting β2-agonist] LABA, LAMA+LABA, LAMA+LABA+ [Inhaled corticosteroid(s)] 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 American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines
  • Ability to produce sputum samples during the induced sputum procedure

Exclusion Criteria:

  • 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 exacerbation, pneumonia, or other respiratory infection in the 12 weeks prior to Screening.
  • 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%)
  • Human immunodeficiency virus (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
  • Taking prohibited medication
  • Prior receipt of Ohtuvayre or blinded nebulized study medication in an ensifentrine (RPL554) study. Note: Other ensifentrine formats (e.g., DPI, MPI) are not exclusionary
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Ensifentrine Sequence 1

In treatment period 1 participants will receive 3 mg ensifentrine twice daily administered via a standard jet nebulizer for 8 weeks followed by treatment period 2 during which participants will receive placebo matching ensifentrine twice daily administered via a standard jet nebulizer for 8 weeks. Throughout treatment sequence 1 participants will receive LABA/LAMA background therapy.
Drug: Ensifentrine

Ensifentrine administered twice daily by oral inhalation via a standard jet nebulizer.

Drug: Placebo

Placebo matching ensifentrine administered twice daily by oral inhalation via a standard jet nebulizer.

Drug: LABA/LAMA

Background treatment of LAMA/LABA administered per product approved label delivered by oral inhalation.

Other Names:
  • Anoro®
Experimental: Ensifentrine Sequence 2

In treatment period 1 participants will receive placebo matching ensifentrine twice daily administered via a standard jet nebulizer for 8 weeks followed by treatment period 2 during which participants will receive 3 mg ensifentrine twice daily administered via a standard jet nebulizer for 8 weeks. Throughout treatment sequence 2 participants will receive LABA/LAMA background therapy.
Drug: Ensifentrine

Ensifentrine administered twice daily by oral inhalation via a standard jet nebulizer.

Drug: Placebo

Placebo matching ensifentrine administered twice daily by oral inhalation via a standard jet nebulizer.

Drug: LABA/LAMA

Background treatment of LAMA/LABA administered per product approved label delivered by oral inhalation.

Other Names:
  • Anoro®

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The Absolute Change From Baseline in Sputum Neutrophil Cell Numbers
Time Frame: Baseline and 8 Weeks

The Absolute change from baseline in sputum neutrophil cell numbers will be reported.
Baseline and 8 Weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Absolute Change in Cell Numbers From Baseline in Sputum Cell Counts
Time Frame: Baseline and 8 Weeks

Absolute change in cell numbers from baseline in sputum cell counts (eosinophils, basophils, macrophages, lymphocytes, total cells) will be reported.
Baseline and 8 Weeks
Percent Change From Baseline in Sputum Cell Counts
Time Frame: Baseline and 8 Weeks

Percent change from baseline in sputum cell counts (neutrophils, eosinophils, basophils, macrophages, lymphocytes, and total cells) will be reported.
Baseline and 8 Weeks
Percent Change From Baseline in Cytokines
Time Frame: Baseline and 8 Weeks

Percent Change From Baseline in Cytokines will be reported.
Baseline and 8 Weeks
Percent Change From Baseline in Proteases
Time Frame: Baseline and 8 Weeks

Percent Change From Baseline in Proteases will be reported.
Baseline and 8 Weeks
Percent Change From Baseline in Markers of Inflammation
Time Frame: Baseline and 8 Weeks

Percent Change From Baseline in Markers of Inflammation will be reported.
Baseline and 8 Weeks
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at 4 Weeks
Time Frame: Baseline and 4 Weeks

Change from baseline in FEV1 at 4 weeks during the treatment period (predose and 2 hours postdose) will be reported.
Baseline and 4 Weeks
Change From Baseline in FEV1 at 8 Weeks
Time Frame: Baseline and 8 Weeks

Change from baseline in FEV1 at 8 weeks during the treatment period (postdose) will be reported.
Baseline and 8 Weeks
Change From Baseline in Forced Vital Capacity (FVC) at 4 Weeks
Time Frame: Baseline and 4 Weeks

Change from baseline in FVC at 4 weeks during the treatment period (predose and 2 hours postdose) will be reported.
Baseline and 4 Weeks
Change From Baseline in FVC at 8 Weeks
Time Frame: Baseline and 8 Weeks

Change from baseline in FVC at 8 weeks during the treatment period (postdose) will be reported.
Baseline and 8 Weeks
Change From Baseline in Residual Volume (RV) at 4 Weeks
Time Frame: Baseline and 4 Weeks

Change from baseline in RV at 4 weeks during the treatment period (predose and 2 hours postdose) will be reported.
Baseline and 4 Weeks
Change From Baseline in RV at 8 Weeks
Time Frame: Baseline and 8 Weeks

Change from baseline in RV at 8 weeks (postdose) during the treatment period will be reported.
Baseline and 8 Weeks
Change From Baseline in Functional Residual Capacity (FRC) at 4 Weeks
Time Frame: Baseline and 4 Weeks

Change from baseline in FRC at 4 weeks during the treatment period (predose and 2 hours postdose) will be reported.
Baseline and 4 Weeks
Change From Baseline in FRC at 8 Weeks
Time Frame: Baseline and 8 Weeks

Change from baseline in FRC at 8 weeks (postdose) during the treatment period will be reported.
Baseline and 8 Weeks
Change From Baseline in Total Lung Capacity (TLC) at 4 Weeks
Time Frame: Baseline and 4 Weeks

Change from baseline in TLC at 4 weeks during the treatment period (predose and 2 hours postdose) will be reported.
Baseline and 4 Weeks
Change From Baseline in TLC at 8 Weeks
Time Frame: Baseline and 8 Weeks

Change from baseline in TLC at 8 weeks (postdose) during the treatment period will be reported.
Baseline and 8 Weeks
Number of Participants Who Experience One or More Adverse Events (AEs)
Time Frame: Up to approximately 8 Weeks

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Number of participants who experience one or more adverse events will be reported.
Up to approximately 8 Weeks
Change From Baseline in Systolic Blood Pressure
Time Frame: Baseline and 8 Weeks

Change from baseline in systolic blood pressure will be reported.
Baseline and 8 Weeks
Change From Baseline in Diastolic Blood Pressure
Time Frame: Baseline and 8 Weeks

Change from baseline in diastolic blood pressure will be reported.
Baseline and 8 Weeks
Change From Baseline in Heart Rate
Time Frame: Baseline and 8 Weeks

Change from baseline in heart rate will be reported.
Baseline and 8 Weeks
Change From Baseline in QRS Duration
Time Frame: Baseline and 8 Weeks

Change from baseline in QRS duration will be reported.
Baseline and 8 Weeks
Change From Baseline in QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF)
Time Frame: Baseline and 8 Weeks

Change from baseline in QTcF will be reported.
Baseline and 8 Weeks
Change From Baseline in QT Interval
Time Frame: Baseline and 8 Weeks

Change from baseline for in QT interval will be reported.
Baseline and 8 Weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Absolute Blood Cell Counts at 4 Weeks
Time Frame: Baseline and 4 Weeks

Change from baseline in absolute blood cell counts at 4 weeks will be reported.
Baseline and 4 Weeks
Change From Baseline in Cytokines at 4 Weeks
Time Frame: Baseline and 4 Weeks

Change From Baseline in Cytokines at 4 Weeks will be reported.
Baseline and 4 Weeks
Change From Baseline in Proteases at 4 Weeks
Time Frame: Baseline and 4 Weeks

Change From Baseline in Proteases at 4 Weeks will be reported.
Baseline and 4 Weeks
Change From Baseline in Markers of Inflammation at 4 Weeks
Time Frame: Baseline and 4 Weeks

Change From Baseline in Markers of Inflammation at 4 Weeks will be reported.
Baseline and 4 Weeks
Change From Baseline in Absolute Blood Cell Counts at 8 Weeks
Time Frame: Baseline and 8 Weeks

Change from baseline in absolute blood cell counts at 8 weeks will be reported.
Baseline and 8 Weeks
Change From Baseline in Cytokines at 8 Weeks
Time Frame: Baseline and 8 Weeks

Change from baseline in cytokines at 8 weeks will be reported.
Baseline and 8 Weeks
Change From Baseline in Proteases at 8 Weeks
Time Frame: Baseline and 8 Weeks

Change from baseline in proteases at 8 weeks will be reported.
Baseline and 8 Weeks
Change From Baseline in Blood Markers of Inflammation at 8 Weeks
Time Frame: Baseline and 8 Weeks

Change from baseline in blood markers of inflammation at 8 weeks will be reported.
Baseline and 8 Weeks
Percent Change From Baseline in Sputum Acetylated Proline-Glycine-Proline (AcPGP) at 8 Weeks
Time Frame: Baseline and 8 Weeks

Percent change from baseline in sputum Acetylated Proline-Glycine-Proline (AcPGP) at 8 weeks will be reported.
Baseline and 8 Weeks
Percent Change From Baseline in Sputum Proline-Glycine-Proline (PGP) at 8 Weeks
Time Frame: Baseline and 8 Weeks

Percent change from baseline in sputum PGP at 8 weeks will be reported.
Baseline and 8 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Verona Pharma, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Alabama at Birmingham

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 27, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 8, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 22, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 8, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 29, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RPL554-CO-207
  • MK-5884-023 (Other Identifier: MSD)
  • RPL554-CO-207 (Other Identifier: VeronaPharma)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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