Pulmonary Disease, Chronic ObstructivePhase 3ENHANCE-3NCT07874815
Ensifentrine (MK-5884) Study for the Prevention of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations in Adults With a History of Moderate or Severe Exacerbations While Receiving Standard of Care (SOC) (MK-5884-031/RPL554/ENHANCE-3)
A Phase 3 study testing Ensifentrine in people with Pulmonary Disease, Chronic Obstructive, run by Merck Sharp & Dohme LLC at 7 sites in United States.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of ensifentrine (MK-5884) compared with placebo for the prevention of moderate and severe COPD exacerbation in adults with COPD and a history of exacerbations while receiving SOC treatment. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- Ensifentrine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,136 participants
- Where
- 7 sitesUnited States
- Study dates
- 2 Nov 2026to 29 Apr 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has a diagnosis of Chronic Obstructive Pulmonary Disease (COPD) that was made ≥12 months prior to randomization
- Has been on the stable treatment with the same standard of care (SOC) with long-acting muscarinic antagonist (LAMA)/long-acting beta-2 agonist (LABA)/inhaled corticosteroid (ICS) or LAMA/LABA (if ICS is not appropriate), for at least 2 months prior to Screening
- Has a documented history of ≥1 moderate or severe COPD exacerbation while on standard of care (SOC) within 1 year of Screening
- Is a current or former cigarette smoker with a history of cigarette smoking ≥10 packyears 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, cigar, and/or e-cigarette/vape use cannot be used to calculate pack-year history.
- Has post-bronchodilator forced expiratory volume 1 (FEV1) ≥25% and <70% of Predicted Normal Value
Who cannot join
- Has a history of intubation for respiratory failure within 1 year of Screening
- Is receiving long-term oxygen therapy defined as >15 hours per day
- Uses chronic bilevel positive airway pressure for treatment of respiratory condition unless for treatment of sleep apnea at a stable pressure for at least 3 months
- Is currently using or has used a biologic therapy (e.g., dupilumab, mepolizumab, or tozorakimab) within 6 months prior to Screening Visit
- Has 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.
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
United States7 sites, 7 recruiting
- Recruiting
Lowcountry Lung & Critical Care, PA ( Site 4413)
Charleston, South Carolina, 29406
Study Coordinator, 843-572-8545
- Recruiting
M3 Wake Research, Inc. ( Site 4440)
Chattanooga, Tennessee, 37421
Study Coordinator, 423-698-4584
- Recruiting
Family First Medical Research Center ( Site 4458)
Hialeah Gardens, Florida, 33016
Study Coordinator, 786-665-9374
- Recruiting
Advanced Pulmonary Research Institute ( Site 4427)
Loxahatchee Groves, Florida, 33470
Study Coordinator, 561-603-6688
- Recruiting
CHEAR Center LLC ( Site 4407)
The Bronx, New York, 10455
Study Coordinator, 347-270-1111
- Recruiting
Velocity Clinical Research ( Site 4464)
Valparaiso, Indiana, 46383
Study Coordinator, 219-464-8302
- Recruiting
Victoria Clinical Research Group ( Site 4430)
Victoria, Texas, 77901
Study Coordinator, 361-210-7869
About this study
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ensifentrine (MK-5884) Versus Placebo for the Prevention of COPD Exacerbations in Adults With a History of Moderate or Severe Exacerbations While Receiving Standard of Care (ENHANCE-3)
The purpose of this study is to evaluate the efficacy and safety of ensifentrine (MK-5884) compared with placebo for the prevention of moderate and severe COPD exacerbation in adults with COPD and a history of exacerbations while receiving SOC treatment. The study will also evaluate the efficacy of ensifentrine compared with placebo in improving lung function, improving health related quality of life, and preventing severe exacerbations.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- Ensifentrine, Placebo, Standard of Care (SOC)
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnsifentrineDrug
Also called MK-5884, RPL554
Delivered twice daily by oral inhalation via a standard jet nebulizer
PlaceboOther
Placebo matched to ensifentrine delivered twice daily by oral inhalation via a standard jet nebulizer
Standard of Care (SOC)Drug
Background treatment of LAMA/LABA/ICS or LAMA/LABA (if ICS is not appropriate) administered per product approved label delivered by oral inhalation as part of standard of care
| Study group | Role | What they receive |
|---|---|---|
| Ensifentrine | Experimental | Participants, who meet the criteria of being on standard of care (SOC) background treatment receive ensifentrine twice a day (bid) by oral inhalation via a standard jet nebulizer for up to 52 weeks. Receives: Drug: Ensifentrine; Drug: Standard of Care (SOC) |
| Placebo | Placebo comparator | Participants, who meet the criteria of being on SOC background treatment receive placebo bid by oral inhalation via a standard jet nebulizer for up to 52 weeks. Receives: Other: Placebo; Drug: Standard of Care (SOC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annualized Rate of Adjudicated Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
The annualized rate of moderate or severe exacerbations over 52 weeks will be reported.
Measured: Up to 52 Weeks
Secondary outcomes (5)
Change From Baseline in Forced Expiratory Volume in One Second Area Under the Curve From 0-4 Hours (FEV1 AUC0-4h)
FEV1 measures the volume of air exhaled during the first second of a forced exhalation maneuver from the point of maximal inspiration. FEV1 AUC0-4h represents the bronchodilator response over the 4-hour period following administration of study intervention. Spirometry will be performed to determine the FEV1. Change from baseline in average FEV1 AUC0-4h on Week 12 will be reported.
Measured: Baseline and Week 12
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score Responder Status
The SGRQ is a 50-item patient-reported outcome (PRO) questionnaire used to evaluate health-related quality of life (HRQOL) in patients with COPD. The questionnaire contains 3 domains: Symptoms (frequency and severity of respiratory symptoms), Activity (effect of disease on common daily physical activities), and Impacts (psychological effects of the disease). The recall period of the questionnaire is over the past 4 weeks. The total score ranges from 0 to 100, with lower scores indicating better health status. A clinically meaningful improvement in HRQOL, as measured by the SGRQ, is defined as a ≥4.0-point decrease in SGRQ total score. HRQOL, as measured by the percentage of SGRQ responders (≥4-point decrease) at Week 24 will be reported.
Measured: Baseline and Week 24
Annualized Rate of Adjudicated Severe COPD Exacerbations
The annualized rate of adjudicated severe COPD exacerbations over 52 weeks will be reported.
Measured: Up to 52 Weeks
Number of Participants with at Least One Adverse Event (AE)
An AE is any untoward medical occurrence in a subject, temporally associated with the use of the study medication, whether or not considered related to the study medication. Number of participants who experience at least one AE will be reported.
Measured: Up to 53 weeks
Number of Participants who Discontinued Study Intervention Due to an Adverse Event
An AE is any untoward medical occurrence in a subject, temporally associated with the use of the study medication, whether or not considered related to the study medication. Number of participants who discontinue study intervention due to an AE will be reported.
Measured: Up to 52 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2026
- Study start2 Nov 2026
- Primary completion29 Apr 2029 (estimated)
- Study completion29 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 2,136 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07874815
- Sponsor's protocol ID
- 5884-031
- Other IDs
- 2026-526255-61-00, U1111-1337-6442, MK-5884-031, RPL554
- Acronym
- ENHANCE-3
- Status last verified
- Nov 2026
- First submitted
- 30 Sep 2026
- Last updated
- 6 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ensifentrine (MK-5884) Versus Placebo for the Prevention of COPD Exacerbations in Adults With a History of Moderate or Severe Exacerbations While Receiving Standard of Care (ENHANCE-3)
- ClinicalTrials.gov ID
- NCT07874815
- Acronym / sponsor ID
- ENHANCE-3 / 5884-031
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,136 participants (estimated)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 2 Nov 2026 (actual)
- Primary completion
- 29 Apr 2029 (estimated)
- Study completion
- 29 Apr 2029 (estimated)
- First posted
- 15 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy and safety of ensifentrine (MK-5884) compared with placebo for the prevention of moderate and severe COPD exacerbation in adults with COPD and a history of exacerbations while receiving SOC treatment. The study will also evaluate the efficacy of ensifentrine compared with placebo in improving lung function, improving health related quality of life, and preventing severe exacerbations.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ensifentrine | Experimental | Drug: Ensifentrine, Drug: Standard of Care (SOC)Participants, who meet the criteria of being on standard of care (SOC) background treatment receive ensifentrine twice a day (bid) by oral inhalation via a standard jet nebulizer for up to 52 weeks. |
| Placebo | Placebo comparator | Other: Placebo, Drug: Standard of Care (SOC)Participants, who meet the criteria of being on SOC background treatment receive placebo bid by oral inhalation via a standard jet nebulizer for up to 52 weeks. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Has a diagnosis of Chronic Obstructive Pulmonary Disease (COPD) that was made ≥12 months prior to randomization
- Has been on the stable treatment with the same standard of care (SOC) with long-acting muscarinic antagonist (LAMA)/long-acting beta-2 agonist (LABA)/inhaled corticosteroid (ICS) or LAMA/LABA (if ICS is not appropriate), for at least 2 months prior to Screening
- Has a documented history of ≥1 moderate or severe COPD exacerbation while on standard of care (SOC) within 1 year of Screening
- Is a current or former cigarette smoker with a history of cigarette smoking ≥10 packyears 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, cigar, and/or e-cigarette/vape use cannot be used to calculate pack-year history.
- Has post-bronchodilator forced expiratory volume 1 (FEV1) ≥25% and <70% of Predicted Normal Value
Key exclusion criteria (5 listed)
- Has a history of intubation for respiratory failure within 1 year of Screening
- Is receiving long-term oxygen therapy defined as >15 hours per day
- Uses chronic bilevel positive airway pressure for treatment of respiratory condition unless for treatment of sleep apnea at a stable pressure for at least 3 months
- Is currently using or has used a biologic therapy (e.g., dupilumab, mepolizumab, or tozorakimab) within 6 months prior to Screening Visit
- Has 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EnsifentrineAlso: MK-5884, RPL554Delivered twice daily by oral inhalation via a standard jet nebulizer | Drug | Ensifentrine |
| PlaceboPlacebo matched to ensifentrine delivered twice daily by oral inhalation via a standard jet nebulizer | Other | Placebo |
| Standard of Care (SOC)Background treatment of LAMA/LABA/ICS or LAMA/LABA (if ICS is not appropriate) administered per product approved label delivered by oral inhalation as part of standard of care | Drug | Ensifentrine, Placebo |
Primary outcome
Annualized Rate of Adjudicated Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
Time frame: Up to 52 Weeks
The annualized rate of moderate or severe exacerbations over 52 weeks will be reported.
5 secondary outcomes
Change From Baseline in Forced Expiratory Volume in One Second Area Under the Curve From 0-4 Hours (FEV1 AUC0-4h)
Time frame: Baseline and Week 12
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score Responder Status
Time frame: Baseline and Week 24
Annualized Rate of Adjudicated Severe COPD Exacerbations
Time frame: Up to 52 Weeks
Number of Participants with at Least One Adverse Event (AE)
Time frame: Up to 53 weeks
Number of Participants who Discontinued Study Intervention Due to an Adverse Event
Time frame: Up to 52 Weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Medical Director study director
Merck Sharp & Dohme LLC
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ensifentrine in people with Pulmonary Disease, Chronic Obstructive, run by Merck Sharp & Dohme LLC at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Toll Free Number (1-888-577-8839, Trialsites@msd.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Annualized Rate of Adjudicated Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Exacerbations (time frame: Up to 52 Weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.