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

• ClinicalTrials.gov Identifier: NCT05612035
• Recruitment Status: Recruiting
• First Posted: November 10, 2022
• Last Update Posted: May 6, 2024
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: November 3, 2022
• First Posted Date: November 10, 2022
• Last Update Posted Date: May 6, 2024
• Actual Study Start Date: March 16, 2023
• Estimated Primary Completion Date: April 7, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 3, 2022)

Mean Change From Baseline in 6-minute Walk Distance (6MWD) at Week 24 [ Time Frame: Baseline and Week 24 ]

6MWD is assessed using the 6-minute walk test (6MWT).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 3, 2022)

• Mean Change From Baseline in 6MWD at Week 12 [ Time Frame: Baseline and Week 12 ]
  6MWD is assessed using the 6-minute walk test (6MWT).
• Mean Change From Baseline in N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) at Week 12 [ Time Frame: Baseline and Week 12 ]
  NT-proBNP was measured at baseline and Week 12.
• Mean Change From Baseline in NT-ProBNP at Week 24 [ Time Frame: Baseline and Week 24 ]
  NT-proBNP was measured at baseline and Week 24
• Percentage of Participants Whose World Health Organization-Functional Class (WHO-FC) Does not Worsen Relative to Baseline at Week 12 [ Time Frame: Baseline and 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.
• Percentage of Participants Whose WHO-FC Does not Worsen Relative to Baseline at Week 24 [ Time Frame: Baseline and 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.
• Percentage of Participants With One or More Adverse Events (AEs) [ Time Frame: Up to Week 104 ]
  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.
• Percentage of Participants who Discontinued Study Treatment due to an AE [ Time Frame: Up to Week 102 ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

Double-blind

Primary Purpose: Treatment

Condition

• Pulmonary Hypertension
• Chronic Obstructive Pulmonary Disease

Intervention

• Drug: MK-5475
  MK-5475 380 µg administered as dry powder inhalation once daily.
• Drug: Placebo
  Placebo administered as dry powder inhalation once daily.

Study Arms

• Experimental: MK-5475
  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).
  Intervention: Drug: MK-5475
• Placebo Comparator: Placebo
  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).
  Interventions:

  • Drug: MK-5475
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 3, 2022): 120
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 23, 2028
• Estimated Primary Completion Date: April 7, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Toll Free Number; 1-888-577-8839; Trialsites@merck.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Colombia, France, Germany, Israel, Italy, Korea, Republic of, Mexico, Peru, South Africa, Spain, Switzerland, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05612035
• Other Study ID Numbers: 5475-013; MK-5475-013 ( Other Identifier: Merck ); 2022-501201-13-00 ( Registry Identifier: EU CT )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: May 2024