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

Phase 2

Recruiting

• Conditions: Pulmonary Hypertension; Chronic Obstructive Pulmonary Disease
• Interventions: Drug: Frespaciguat; Drug: Placebo

• Registration Number: NCT05612035
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-11-03
• Study First Submitted QC: 2022-11-03
• Study First Posted: 2022-11-10
• Study Start: 2023-03-16
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-14
• Last Update Posted: 2025-05-18
• Primary Completion: 2026-04-07
• Study Completion: 2029-10-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

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.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Frespaciguat	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).
Placebo	Frespaciguat	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).
Placebo	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).

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Mean Change From Baseline in 6MWD at Week 12	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	Baseline and Week 12	NT-proBNP was measured at baseline and Week 12.
Mean Change From Baseline in NT-ProBNP at Week 24	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	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	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)	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.
Percentage of Participants who Discontinued Study Treatment due to an AE	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.

Trial Locations

Locations (84)

UCSF Helen Diller Medical Center at Parnassus Heights ( Site 0110); 🇺🇸 San Francisco, California, United States

University of Colorado Anschutz Medical Campus-University of Colorado Hospital Cardiac and Vascular ( Site 0101); 🇺🇸 Aurora, Colorado, United States

Clinovation Intl. Corp. ( Site 0108); 🇺🇸 Sebring, Florida, United States

Alexian Brothers Medical Center-Pulmonary ( Site 0109); 🇺🇸 Elk Grove Village, Illinois, United States

University of Iowa ( Site 0103); 🇺🇸 Iowa City, Iowa, United States

University of Kansas Medical Center-IM-Pulmonary and Critical Care Medicine ( Site 0102); 🇺🇸 Kansas City, Kansas, United States

Lexington VA Medical Center - Cooper Division ( Site 0137); 🇺🇸 Lexington, Kentucky, United States

Corewell Health ( Site 0133); 🇺🇸 Grand Rapids, Michigan, United States

Mayo Clinic in Rochester, Minnesota ( Site 0131); 🇺🇸 Rochester, Minnesota, United States

Creighton University Clinical Research Office ( Site 0123); 🇺🇸 Omaha, Nebraska, United States

University of New Mexico Hospital ( Site 0146); 🇺🇸 Albuquerque, New Mexico, United States

UNC Health - Eastowne Medical Office-Clinical Trials Unit ( Site 0147); 🇺🇸 Chapel Hill, North Carolina, United States

Temple University Hospital ( Site 0104); 🇺🇸 Philadelphia, Pennsylvania, United States

UPMC Montefiore University Hospital-Department of Medicine ( Site 0149); 🇺🇸 Pittsburgh, Pennsylvania, United States

UT Southwestern Medical Center ( Site 0114); 🇺🇸 Dallas, Texas, United States

The University of Texas Health Science Center at Houston ( Site 0105); 🇺🇸 Houston, Texas, United States

Intermountain Medical Center-Division of Pulmonary & Critical Care Medicine ( Site 0140); 🇺🇸 Murray, Utah, United States

University of Virginia Health System-Division of Pulmonary and Critical Care Medicine ( Site 0111); 🇺🇸 Charlottesville, Virginia, United States

Fundación Respirar ( Site 0305); 🇦🇷 Caba, Buenos Aires, Argentina

Centro Medico Capital ( Site 0301); 🇦🇷 La PLata, Buenos Aires, Argentina

Instituto de Cardiologia de Tucuman-Area de Investigacion Clinica ( Site 0303); 🇦🇷 San Miguel de Tucumán, Tucuman, Argentina

Hospital Britanico de Buenos Aires ( Site 0307); 🇦🇷 Caba, Argentina

Hospital Privado Universitario de Córdoba-Clinical Cardiology Department ( Site 0302); 🇦🇷 Cordoba, Argentina

Royal Prince Alfred Hospital-Department of Respiratory Medicine ( Site 0903); 🇦🇺 Camperdown, New South Wales, Australia

Westmead Hospital ( Site 0902); 🇦🇺 Westmead, New South Wales, Australia

WESLEY RESEARCH INSTITUTE Limited ( Site 0906); 🇦🇺 Auchenflower, Queensland, Australia

The Prince Charles Hospital ( Site 0904); 🇦🇺 Brisbane, Queensland, Australia

Mater Misericordiae Limited ( Site 0905); 🇦🇺 South Brisbane, Queensland, Australia

Medizinische Universität Graz-Klinische Abteilung für Pulmonologie ( Site 1201); 🇦🇹 Graz, Steiermark, Austria

Medizinische Universitaet Innsbruck ( Site 1202); 🇦🇹 Innsbruck, Tirol, Austria

Université Libre de Bruxelles - Hôpital Erasme ( Site 1302); 🇧🇪 Brussels, Bruxelles-Capitale, Region De, Belgium

UZ Leuven ( Site 1301); 🇧🇪 Leuven, Vlaams-Brabant, Belgium

Clinica Cardio VID ( Site 0504); 🇨🇴 Medellín, Antioquia, Colombia

Ciensalud Ips S A S ( Site 0508); 🇨🇴 Barranquilla, Atlantico, Colombia

Fundación Valle del Lili ( Site 0509); 🇨🇴 Cali, Valle Del Cauca, Colombia

Centro de Investigaciones Clinicas SAS ( Site 0505); 🇨🇴 Cali, Valle Del Cauca, Colombia

C.H.U Hôpital Nord ( Site 1503); 🇫🇷 Marseille, Bouches-du-Rhone, France

Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois ( Site 1502); 🇫🇷 Vandoeuvre lès Nancy, Lorraine, France

CHU Angers ( Site 1506); 🇫🇷 Angers, Maine-et-Loire, France

Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre-Pneumologie ( Site 1501); 🇫🇷 Le Kremlin-Bicêtre, Paris, France

Centre Hospitalier Universitaire de Poitiers ( Site 1505); 🇫🇷 Poitiers, Vienne, France

Thoraxklinik-Heidelberg gGmbH-Zentrum für Pulmonale Hypertonie ( Site 1603); 🇩🇪 Heidelberg, Baden-Wurttemberg, Germany

UKGM Gießen/Marburg ( Site 1604); 🇩🇪 Gießen, Hessen, Germany

Medizinische Hochschule Hannover ( Site 1602); 🇩🇪 Hannover, Niedersachsen, Germany

Universitaetsklinikum Carl Gustav Carus Dresden ( Site 1601); 🇩🇪 Dresden, Sachsen, Germany

Universitätsklinikum Schleswig-Holstein-Pneumologie ( Site 1605); 🇩🇪 Luebeck, Schleswig-Holstein, Germany

Unidad De Diagnostico Cardiologico-Unidad de Diagnostico Cardiologico ( Site 0605); 🇬🇹 Guatemala City, Guatemala

Private Practice - Dr. Jeremias Guerra Mejia ( Site 0603); 🇬🇹 Guatemala City, Guatemala

MEDI-K ( Site 0607); 🇬🇹 Guatemala, Guatemala

Clinica Medica ( Site 0601); 🇬🇹 Guatemala, Guatemala

Rambam Health Care Campus ( Site 1701); 🇮🇱 Haifa, Israel

Rabin Medical Center ( Site 1702); 🇮🇱 Petah Tikva, Israel

Cattinara Hospital ( Site 1801); 🇮🇹 Trieste, Friuli-Venezia Giulia, Italy

Ospedale San Gerardo-ASST Monza-Cardio Vasolare- Clinica pneumologica ( Site 1802); 🇮🇹 Monza, Lombardia, Italy

ISMETT Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione ( Site 1804); 🇮🇹 Palermo, Italy

Gachon University Gil Medical Center ( Site 1101); 🇰🇷 Namdong-gu, Incheon, Korea, Republic of

Seoul National University Hospital ( Site 1103); 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center ( Site 1102); 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center ( Site 1104); 🇰🇷 Seoul, Korea, Republic of

Centro Médico Nacional Siglo XXI ( Site 0708); 🇲🇽 Mexico City, Distrito Federal, Mexico

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0704); 🇲🇽 Mexico City, Distrito Federal, Mexico

INVECORDIS S.C. ( Site 0703); 🇲🇽 Hacienda De Las Palmas, Mexico

Instituto Nacional de Cardiologia Ignacio Chavez ( Site 0701); 🇲🇽 Mexico, Mexico

Unidad de Investigacon de la Clinica Internacional ( Site 0804); 🇵🇪 Cercado De Lima, Lima, Peru

Clinica Ricardo Palma-Centro de Investigacion de Enfermedades Respiratorias Thorax ( Site 0806); 🇵🇪 San Isidro, Lima, Peru

Clínica Providencia ( Site 0803); 🇵🇪 San Miguel, Lima, Peru

Charlotte Maxeke Johannesburg Academic Hospital ( Site 2108); 🇿🇦 Johannesburg, Gauteng, South Africa

Netcare Milpark Hospital ( Site 2103); 🇿🇦 Johannesburg, Gauteng, South Africa

Netcare St Augustine's Hospital ( Site 2105); 🇿🇦 Durban, Kwazulu-Natal, South Africa

TREAD Research ( Site 2101); 🇿🇦 Cape Town, Western Cape, South Africa

Hospital Universitario Marqués de Valdecilla-Pneumology ( Site 2003); 🇪🇸 Santander, Cantabria, Spain

HOSPITAL CLÍNIC DE BARCELONA ( Site 2001); 🇪🇸 Barcelona, Cataluna, Spain

Parc de Salut Mar - Hospital del Mar ( Site 2006); 🇪🇸 Barcelona, Spain

Hospital Universitari Vall d'Hebron ( Site 2002); 🇪🇸 Barcelona, Spain

HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO ( Site 2005); 🇪🇸 Sevilla, Spain

University Hospital Basel ( Site 2205); 🇨🇭 Basel, Basel-Stadt, Switzerland

UniversitätsSpital Zürich ( Site 2201); 🇨🇭 Zürich, Zurich, Switzerland

Cantonal Hospital St.Gallen ( Site 2203); 🇨🇭 Sankt Gallen, Switzerland

Hacettepe Universite Hastaneleri ( Site 2301); 🇹🇷 Ankara, Turkey

Ankara Bilkent Şehir Hastanesi. ( Site 2307); 🇹🇷 Ankara, Turkey

Eskisehir Osmangazi University-Cardiology ( Site 2304); 🇹🇷 Eskisehir, Turkey

Istanbul Universitesi Istanbul Tıp Fakultesi Hastanesi-Chest Disease ( Site 2302); 🇹🇷 Istanbul, Turkey

Hammersmith Hospital-Department of Cardiology ( Site 2401); 🇬🇧 London, London, City Of, United Kingdom

Sheffield Teaching Hospitals NHS Foundation Trust-Clinical Research Facility ( Site 2405); 🇬🇧 Sheffield, United Kingdom