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

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05612035
Collaborator
(none)
120
1
2
43.6
2.8

Study Details

Study Description

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 80 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
Double-blind
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Jan 27, 2023
Anticipated Primary Completion Date :
Mar 14, 2025
Anticipated Study Completion Date :
Sep 15, 2026

Arms and Interventions

Arm Intervention/Treatment
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).

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

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).

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

Drug: Placebo
Placebo administered as dry powder inhalation once daily.

Outcome Measures

Primary Outcome Measures

  1. Mean Change From Baseline in 6-minute Walk Distance (6MWD) at Week 24 [Baseline and Week 24]

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

Secondary Outcome Measures

  1. Mean Change From Baseline in 6MWD at Week 12 [Baseline and Week 12]

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

  2. Mean Change From Baseline in N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) at Week 12 [Baseline and Week 12]

    NT-proBNP was measured at baseline and Week 12.

  3. Mean Change From Baseline in NT-ProBNP at Week 24 [Baseline and Week 24]

    NT-proBNP was measured at baseline and Week 24

  4. Percentage of Participants Whose World Health Organization-Functional Class (WHO-FC) Does not Worsen Relative to Baseline at Week 12 [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.

  5. Percentage of Participants Whose WHO-FC Does not Worsen Relative to Baseline at Week 24 [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.

  6. Percentage of Participants With One or More Adverse Events (AEs) [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.

  7. Percentage of Participants who Discontinued Study Treatment due to an AE [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
40 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 evidence 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 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 80 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 history of Group 1 pulmonary arterial hypertension (PAH), Groups 2, 4 or 5 pulmonary hypertension (PH).

  • Has history of non-COPD related Group 3 PH.

  • Has evidence of untreated more than mild obstructive sleep apnea.

  • Has evidence or history of 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) < 90%.

  • 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Lexington VA Medical Center - Cooper Division ( Site 0137) Lexington Kentucky United States 40502

Sponsors and Collaborators

  • Merck Sharp & Dohme LLC

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT05612035
Other Study ID Numbers:
  • 5475-013
  • MK-5475-013
  • 2022-501201-13-00
First Posted:
Nov 10, 2022
Last Update Posted:
Jan 10, 2023
Last Verified:
Jan 1, 2023
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 10, 2023