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

April 30, 2026 updated by: Merck Sharp & Dohme LLC

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

Researchers are looking for ways to treat pulmonary hypertension (PH) caused by chronic obstructive pulmonary disease (COPD). The goal of the study is to learn if people who take frespaciguat can walk farther in 6 minutes at Week 24 compared to people who take placebo.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

129

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • CABA, Argentina, C1280AEB
        • Hospital Britanico de Buenos Aires ( Site 0307)
      • Córdoba, Argentina, X5016KEH
        • Hospital Privado Universitario de Córdoba-Clinical Cardiology Department ( Site 0302)
    • Buenos Aires
      • CABA, Buenos Aires, Argentina, C1426ABP
        • Fundación Respirar ( Site 0305)
      • La Plata, Buenos Aires, Argentina, 1904
        • Centro Medico Capital ( Site 0301)
    • Tucumán Province
      • San Miguel de Tucumán, Tucumán Province, Argentina, 4000
        • Instituto de Cardiologia de Tucuman-Area de Investigacion Clinica ( Site 0303)
  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Royal Prince Alfred Hospital-Department of Respiratory Medicine ( Site 0903)
      • Westmead, New South Wales, Australia, 2145
        • Westmead Hospital ( Site 0902)
    • Queensland
      • Auchenflower, Queensland, Australia, 4066
        • WESLEY RESEARCH INSTITUTE Limited ( Site 0906)
      • Brisbane, Queensland, Australia, 4032
        • The Prince Charles Hospital ( Site 0904)
      • South Brisbane, Queensland, Australia, 4101
        • Mater Misericordiae Limited ( Site 0905)
  • Austria
    • Styria
      • Graz, Styria, Austria, 8036
        • Medizinische Universität Graz-Klinische Abteilung für Pulmonologie ( Site 1201)
    • Tyrol
      • Innsbruck, Tyrol, Austria, 6020
        • Medizinische Universitaet Innsbruck ( Site 1202)
  • Belgium
    • Bruxelles-Capitale, Region de
      • Brussels, Bruxelles-Capitale, Region de, Belgium, 1070
        • Université Libre de Bruxelles - Hôpital Erasme ( Site 1302)
    • Vlaams-Brabant
      • Leuven, Vlaams-Brabant, Belgium, 3000
        • UZ Leuven ( Site 1301)
  • Colombia
    • Antioquia
      • Medellín, Antioquia, Colombia, 050034
        • Clinica Cardio VID ( Site 0504)
    • Atlántico
      • Barranquilla, Atlántico, Colombia, 080001
        • Ciensalud Ips S A S ( Site 0508)
    • Valle del Cauca Department
      • Cali, Valle del Cauca Department, Colombia, 760032
        • Fundación Valle del Lili ( Site 0509)
      • Cali, Valle del Cauca Department, Colombia, 760036
        • Centro de Investigaciones Clinicas SAS ( Site 0505)
  • France
    • Bouches-du-Rhone
      • Marseille, Bouches-du-Rhone, France, 13915
        • C.H.U Hôpital Nord ( Site 1503)
    • Lorraine
      • Vandœuvre-lès-Nancy, Lorraine, France, 54511
        • Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois ( Site 1502)
    • Maine-et-Loire
      • Angers, Maine-et-Loire, France, 49933
        • CHU Angers ( Site 1506)
    • Paris
      • Le Kremlin-Bicêtre, Paris, France, 94270
        • Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre-Pneumologie ( Site 1501)
    • Vienne
      • Poitiers, Vienne, France, 86021
        • Centre Hospitalier Universitaire de Poitiers ( Site 1505)
  • Germany
    • Baden-Wurttemberg
      • Heidelberg, Baden-Wurttemberg, Germany, 69126
        • Thoraxklinik-Heidelberg gGmbH-Zentrum für Pulmonale Hypertonie ( Site 1603)
    • Hesse
      • Giessen, Hesse, Germany, 35392
        • UKGM Gießen/Marburg ( Site 1604)
    • Lower Saxony
      • Hanover, Lower Saxony, Germany, 30625
        • Medizinische Hochschule Hannover ( Site 1602)
    • Saxony
      • Dresden, Saxony, Germany, 01307
        • Universitaetsklinikum Carl Gustav Carus Dresden ( Site 1601)
    • Schleswig-Holstein
      • Lübeck, Schleswig-Holstein, Germany, 23538
        • Universitätsklinikum Schleswig-Holstein-Pneumologie ( Site 1605)
  • Guatemala
      • Guatemala City, Guatemala, 01001
        • Unidad De Diagnostico Cardiologico-Unidad de Diagnostico Cardiologico ( Site 0605)
      • Guatemala City, Guatemala, 01009
        • MEDI-K ( Site 0607)
      • Guatemala City, Guatemala, 01010
        • Clinica Medica ( Site 0601)
      • Guatemala City, Guatemala, 01010
        • Private Practice - Dr. Jeremias Guerra Mejia ( Site 0603)
  • Israel
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus ( Site 1701)
      • Petah Tikva, Israel, 4941 492
        • Rabin Medical Center ( Site 1702)
  • Italy
      • Palermo, Italy, 90127
        • ISMETT Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione ( Site 1804)
    • Friuli Venezia Giulia
      • Trieste, Friuli Venezia Giulia, Italy, 34149
        • Cattinara Hospital ( Site 1801)
    • Lombardy
      • Monza, Lombardy, Italy, 20900
        • Ospedale San Gerardo-ASST Monza-Cardio Vasolare- Clinica pneumologica ( Site 1802)
  • Mexico
      • México, Mexico, 14080
        • Instituto Nacional de Cardiologia Ignacio Chavez ( Site 0701)
    • Mexico City
      • Mexico City, Mexico City, Mexico, 06760
        • Centro Médico Nacional Siglo XXI ( Site 0708)
      • Mexico City, Mexico City, Mexico, 14080
        • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0704)
    • State of Mexico
      • Hacienda de Las Palmas, State of Mexico, Mexico, 52787
        • INVECORDIS S.C. ( Site 0703)
  • Peru
    • Lima region
      • Lima Cercado, Lima region, Peru, 15001
        • Unidad de Investigacon de la Clinica Internacional ( Site 0804)
      • San Isidro, Lima region, Peru, 15036
        • Clinica Ricardo Palma-Centro de Investigacion de Enfermedades Respiratorias Thorax ( Site 0806)
      • San Miguel, Lima region, Peru, 15088
        • Clínica Providencia ( Site 0803)
  • South Africa
    • Gauteng
      • Johannesburg, Gauteng, South Africa, 2193
        • Charlotte Maxeke Johannesburg Academic Hospital ( Site 2108)
      • Johannesburg, Gauteng, South Africa, 2193
        • Netcare Milpark Hospital ( Site 2103)
    • KwaZulu-Natal
      • Durban, KwaZulu-Natal, South Africa, 4001
        • Netcare St Augustine's Hospital ( Site 2105)
    • Western Cape
      • Cape Town, Western Cape, South Africa, 7500
        • TREAD Research ( Site 2101)
  • South Korea
      • Seoul, South Korea, 03080
        • Seoul National University Hospital ( Site 1103)
      • Seoul, South Korea, 05505
        • Asan Medical Center ( Site 1102)
      • Seoul, South Korea, 06355
        • Samsung Medical Center ( Site 1104)
    • Incheon
      • Namdong-gu, Incheon, South Korea, 21565
        • Gachon University Gil Medical Center ( Site 1101)
  • Spain
      • Barcelona, Spain, 08003
        • Parc de Salut Mar - Hospital del Mar ( Site 2006)
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron ( Site 2002)
      • Seville, Spain, 41013
        • HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO ( Site 2005)
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Hospital Universitario Marqués de Valdecilla-Pneumology ( Site 2003)
    • Catalonia
      • Barcelona, Catalonia, Spain, 08036
        • HOSPITAL CLÍNIC DE BARCELONA ( Site 2001)
  • Switzerland
      • Sankt Gallen, Switzerland, 9007
        • Cantonal Hospital St.Gallen ( Site 2203)
    • Canton of Basel-City
      • Basel, Canton of Basel-City, Switzerland, 4031
        • University Hospital Basel ( Site 2205)
    • Canton of Zurich
      • Zurich, Canton of Zurich, Switzerland, 8091
        • UniversitätsSpital Zürich ( Site 2201)
  • Turkey (Türkiye)
      • Ankara, Turkey (Türkiye), 06230
        • Hacettepe Universite Hastaneleri ( Site 2301)
      • Ankara, Turkey (Türkiye), 06800
        • Ankara Bilkent Şehir Hastanesi. ( Site 2307)
      • Ankara, Turkey (Türkiye), 6100
        • Ankara University Health Practice and Research Hospitals ( Site 2310)
      • Eskişehir, Turkey (Türkiye), 26480
        • Eskisehir Osmangazi University-Cardiology ( Site 2304)
      • Istanbul, Turkey (Türkiye), 34093
        • Istanbul Universitesi Istanbul Tıp Fakultesi Hastanesi-Chest Disease ( Site 2302)
  • United Kingdom
      • Sheffield, United Kingdom, S10 2JF
        • Sheffield Teaching Hospitals NHS Foundation Trust-Clinical Research Facility ( Site 2405)
    • London, City of
      • London, London, City of, United Kingdom, W12 OHS
        • Hammersmith Hospital-Department of Cardiology ( Site 2401)
  • United States
    • California
      • San Francisco, California, United States, 94143
        • UCSF Helen Diller Medical Center at Parnassus Heights ( Site 0110)
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Anschutz Medical Campus-University of Colorado Hospital Cardiac and Vascular ( Site 0101)
    • Florida
      • Sebring, Florida, United States, 33870
        • Clinovation Intl. Corp. ( Site 0108)
    • Illinois
      • Elk Grove Village, Illinois, United States, 60007
        • Alexian Brothers Medical Center-Pulmonary ( Site 0109)
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa ( Site 0103)
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center-IM-Pulmonary and Critical Care Medicine ( Site 0102)
    • Kentucky
      • Lexington, Kentucky, United States, 40502
        • Lexington VA Medical Center - Cooper Division ( Site 0137)
    • Michigan
      • Grand Rapids, Michigan, United States, 49546
        • Corewell Health ( Site 0133)
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester, Minnesota ( Site 0131)
    • Nebraska
      • Omaha, Nebraska, United States, 68124
        • Creighton University Clinical Research Office ( Site 0123)
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico Hospital ( Site 0146)
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • UNC Health - Eastowne Medical Office-Clinical Trials Unit ( Site 0147)
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University Hospital ( Site 0104)
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC Montefiore University Hospital-Department of Medicine ( Site 0149)
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center ( Site 0114)
      • Houston, Texas, United States, 77030
        • The University of Texas Health Science Center at Houston ( Site 0105)
    • Utah
      • Murray, Utah, United States, 84107
        • Intermountain Medical Center-Division of Pulmonary & Critical Care Medicine ( Site 0140)
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Health System-Division of Pulmonary and Critical Care Medicine ( Site 0111)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 frespaciguat as an oral inhalation once daily for up to 42 months (optional extension period).
Drug: Placebo
Placebo administered as dry powder inhalation once daily.
Drug: Frespaciguat
Frespaciguat 380 µg administered as dry powder inhalation once daily.
Other Names:
  • MK-5475
Experimental: Frespaciguat
Participants with PH-COPD will receive 380 µg of frespaciguat as an oral inhalation once daily for 24 weeks (base period) and thereafter for up to 42 months (optional extension period).
Drug: Frespaciguat
Frespaciguat 380 µg administered as dry powder inhalation once daily.
Other Names:
  • MK-5475

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Baseline and Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Baseline and Week 12
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.
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
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.
Baseline and Week 12
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.
Baseline and Week 24
Percentage of Participants With One or More Adverse Events (AEs)
Time Frame: Up to Week 206
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 206
Percentage of Participants who Discontinued Study Treatment due to an AE
Time Frame: Up to Week 204
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 204

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 16, 2023

Primary Completion (Actual)

April 9, 2026

Study Completion (Estimated)

October 8, 2029

Study Registration Dates

First Submitted

November 3, 2022

First Submitted That Met QC Criteria

November 3, 2022

First Posted (Actual)

November 10, 2022

Study Record Updates

Last Update Posted (Actual)

May 1, 2026

Last Update Submitted That Met QC Criteria

April 30, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5475-013
  • MK-5475-013 (Other Identifier: MSD)
  • 2022-501201-13-00 (Registry Identifier: EU CT)
  • U1111-1279-8512 (Registry Identifier: UTN)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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