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)

NCT07874815 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 5 other identifiers: 5884-0312026-526255-61-00U1111-1337-6442MK-5884-031RPL554
• Study Type: interventional
• Target: 2,136
• Locations: 0 countries
• Sites: N/A

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• 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.

  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)

  Baseline and Week 12

• Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score Responder Status

  Baseline and Week 24

• Annualized Rate of Adjudicated Severe COPD Exacerbations

  Up to 52 Weeks

• Number of Participants with at Least One Adverse Event (AE)

  Up to 53 weeks

• Number of Participants who Discontinued Study Intervention Due to an Adverse Event

  Up to 52 Weeks

Study Arms (2)

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.

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.

Other: Placebo; Drug: Standard of Care (SOC)

Interventions

Ensifentrine DRUG

Delivered twice daily by oral inhalation via a standard jet nebulizer

Also known as: MK-5884, RPL554

Ensifentrine

Placebo OTHER

Placebo matched to ensifentrine delivered twice daily by oral inhalation via a standard jet nebulizer

Placebo

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

Ensifentrine; Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

ensifentrine; Standard of Care

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)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2026
• First Posted: October 15, 2026
• Study Start (Estimated): October 23, 2026
• Primary Completion (Estimated): April 29, 2029
• Study Completion (Estimated): April 29, 2029
• Last Updated: October 15, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will share