MK-5475-013 INSIGNIA-PH-COPD: A Study of the Efficacy and Safety of MK-5475 (an Inhaled sGC Stimulator) in Adults With PH-COPD

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of once daily oral inhalation dose of MK-5475 380 µg in participants 40 to 85 years (inclusive) with Pulmonary Hypertension associated with Chronic Obstructive Pulmonary Disease (PH-COPD). The primary hypothesis of the study is MK-5475, a soluble Guanylate Cyclase (sGC) stimulator is superior to placebo in increasing 6 Minute Walking Distance (6MWD) from baseline at Week 24.

Official Title
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A Phase 2a Randomized, Placebo-Controlled Clinical Study to Evaluate the Efficacy and Safety of MK-5475 in Adults With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease

Conditions
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Pulmonary Hypertension, Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: MK-5475
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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The key inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: Has Group 3.1 pulmonary hypertension chronic obstructive pulmonary disease (PH-COPD) as defined by the Clinical Classification of Pulmonary Hypertension. Has a right heart catheterization (RHC) at screening or historical RHC within 12 months before screening that meets hemodynamic criteria. Has a physician diagnosis of obstructive lung disease on pulmonary function testing (PFT) performed at screening. Has a WHO Functional Class assessment of Class II to IV. If on supplemental oxygen, the regimen must be stable. Has stable and optimized chronic, baseline COPD-specific therapy. If on PDE5 inhibitor, has stable concomitant use (initiated at least 3 months prior to randomization and no change in drug or dosage for at least 3 months prior to randomization) and changes to PDE5 inhibitor dosing is not anticipated during the 24 week Base Period. If on antihypertensives and/or a diuretic regimen has stable concomitant use. If on anticoagulants has stable concomitant use. Is of any sex/gender from 40 to 85 years of age inclusive. Female is not pregnant or breastfeeding, and is not of childbearing potential or uses acceptable contraceptive method or abstains from sexual intercourse, or has a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention, or whose history and sexual activity has been reviewed by the investigator. Exclusion criteria: Has Group 1 pulmonary arterial hypertension (PAH), Groups 2, 4 or 5 pulmonary hypertension (PH). Has non-COPD related Group 3 PH. Has evidence of untreated more than mild obstructive sleep apnea. Has significant left heart disease. Expects to receive a lung and/or heart transplant from screening through the end of the 24 week Base Period. Has evidence of a resting oxygen saturation (SpO2) < 88%. Has experienced a moderate or severe COPD exacerbation within 2 months before randomization. Has experienced right heart failure within 2 months before randomization. Has uncontrolled tachyarrhythmia. Has acute coronary syndrome, undergone coronary artery bypass graft, or percutaneous coronary intervention within 2 months before randomization. Has evidence of significant chronic renal insufficiency. Has evidence of chronic liver disease, portal hypertension, cirrhosis, or hepatic abnormalities. Initiated a pulmonary rehabilitation program within 2 months before randomization. Has impairments that limit the ability to perform 6MWT. Has history of cancer. Is a user of illicit drugs or has a recent history of drug/alcohol abuse or dependence. Has used PAH-specific therapies within 2 months of randomization.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-5475<br>Participants with PH-COPD will receive 380 µg of MK-5475 as an oral inhalation once daily for 24 weeks (base period) and thereafter for 18 months (optional extension period). | Drug: MK-5475<br>* MK-5475 380 µg administered as dry powder inhalation once daily.<br>|
| Placebo Comparator: Placebo<br>Participants with PH-COPD will receive matching placebo as an oral inhalation once daily for 24 weeks (base period) and then 380 µg of MK-5475 as an oral inhalation once daily for 18 months (optional extension period). | Drug: MK-5475<br>* MK-5475 380 µg administered as dry powder inhalation once daily.<br>Drug: Placebo<br>* Placebo administered as dry powder inhalation once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in 6-minute Walk Distance (6MWD) at Week 24 | 6MWD is assessed using the 6-minute walk test (6MWT). | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in 6MWD at Week 12 | 6MWD is assessed using the 6-minute walk test (6MWT). | Baseline and Week 12 | 
| Mean Change From Baseline in N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) at Week 12 | NT-proBNP was measured at baseline and Week 12. | Baseline and Week 12 | 
| Mean Change From Baseline in NT-ProBNP at Week 24 | NT-proBNP was measured at baseline and Week 24 | Baseline and Week 24 | 
| Percentage of Participants Whose World Health Organization-Functional Class (WHO-FC) Does not Worsen Relative to Baseline at Week 12 | Participants are assigned one of four WHO-FC, dependent on limits of physical activity. As WHO-FC increases from I to IV, limits of physical activity increase. | Baseline and Week 12 | 
| Percentage of Participants Whose WHO-FC Does not Worsen Relative to Baseline at Week 24 | Participants are assigned one of four WHO-FC, dependent on limits of physical activity. As WHO-FC increases from I to IV, limits of physical activity increase. | Baseline and Week 24 | 
| Percentage of Participants With One or More Adverse Events (AEs) | An adverse event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. | Up to Week 104 | 
| Percentage of Participants who Discontinued Study Treatment due to an AE | An adverse event (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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinue study treatment due to an AE will be presented. | Up to Week 102 |