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

NCT05612035 | Active Not Recruiting Phase 2 FDA Drug

• 4 other identifiers: 5475-013MK-5475-0132022-501201-13-00U1111-1279-8512
• Study Type: interventional
• Target: 129
• Locations: 18 countries
• Sites: 80

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.

Conditions

Chronic Obstructive Pulmonary Disease; Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Mean Change From Baseline in 6MWD at Week 12

  Baseline and Week 12

• Mean Change From Baseline in N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) at Week 12

  Baseline and Week 12

• Mean Change From Baseline in NT-ProBNP at 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

  Baseline and Week 12

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

  Baseline and Week 24

Study Arms (2)

Frespaciguat

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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: Frespaciguat; Drug: Placebo

Interventions

Frespaciguat DRUG

Frespaciguat 380 µg administered as dry powder inhalation once daily.

Also known as: MK-5475

Frespaciguat; Placebo

Placebo DRUG

Placebo administered as dry powder inhalation once daily.

Placebo

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (85)

UCSF Helen Diller Medical Center at Parnassus Heights ( Site 0110)

San Francisco, California, 94143, United States

Location

University of Colorado Anschutz Medical Campus-University of Colorado Hospital Cardiac and Vascular ( Site 0101)

Aurora, Colorado, 80045, United States

Location

Clinovation Intl. Corp. ( Site 0108)

Sebring, Florida, 33870, United States

Location

Alexian Brothers Medical Center-Pulmonary ( Site 0109)

Elk Grove Village, Illinois, 60007, United States

Location

University of Iowa ( Site 0103)

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center-IM-Pulmonary and Critical Care Medicine ( Site 0102)

Kansas City, Kansas, 66160, United States

Location

Lexington VA Medical Center - Cooper Division ( Site 0137)

Lexington, Kentucky, 40502, United States

Location

Corewell Health ( Site 0133)

Grand Rapids, Michigan, 49546, United States

Location

Mayo Clinic in Rochester, Minnesota ( Site 0131)

Rochester, Minnesota, 55905, United States

Location

Creighton University Clinical Research Office ( Site 0123)

Omaha, Nebraska, 68124, United States

Location

University of New Mexico Hospital ( Site 0146)

Albuquerque, New Mexico, 87106, United States

Location

UNC Health - Eastowne Medical Office-Clinical Trials Unit ( Site 0147)

Chapel Hill, North Carolina, 27514, United States

Location

Temple University Hospital ( Site 0104)

Philadelphia, Pennsylvania, 19140, United States

Location

UPMC Montefiore University Hospital-Department of Medicine ( Site 0149)

Pittsburgh, Pennsylvania, 15213, United States

Location

UT Southwestern Medical Center ( Site 0114)

Dallas, Texas, 75390, United States

Location

The University of Texas Health Science Center at Houston ( Site 0105)

Houston, Texas, 77030, United States

Location

Intermountain Medical Center-Division of Pulmonary & Critical Care Medicine ( Site 0140)

Murray, Utah, 84107, United States

Location

University of Virginia Health System-Division of Pulmonary and Critical Care Medicine ( Site 0111)

Charlottesville, Virginia, 22908, United States

Location

Fundación Respirar ( Site 0305)

CABA, Buenos Aires, C1426ABP, Argentina

Location

Centro Medico Capital ( Site 0301)

La Plata, Buenos Aires, 1904, Argentina

Location

Instituto de Cardiologia de Tucuman-Area de Investigacion Clinica ( Site 0303)

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

Hospital Britanico de Buenos Aires ( Site 0307)

CABA, C1280AEB, Argentina

Location

Hospital Privado Universitario de Córdoba-Clinical Cardiology Department ( Site 0302)

Córdoba, X5016KEH, Argentina

Location

Royal Prince Alfred Hospital-Department of Respiratory Medicine ( Site 0903)

Camperdown, New South Wales, 2050, Australia

Location

Westmead Hospital ( Site 0902)

Westmead, New South Wales, 2145, Australia

Location

WESLEY RESEARCH INSTITUTE Limited ( Site 0906)

Auchenflower, Queensland, 4066, Australia

Location

The Prince Charles Hospital ( Site 0904)

Brisbane, Queensland, 4032, Australia

Location

Mater Misericordiae Limited ( Site 0905)

South Brisbane, Queensland, 4101, Australia

Location

Medizinische Universität Graz-Klinische Abteilung für Pulmonologie ( Site 1201)

Graz, Styria, 8036, Austria

Location

Medizinische Universitaet Innsbruck ( Site 1202)

Innsbruck, Tyrol, 6020, Austria

Location

Université Libre de Bruxelles - Hôpital Erasme ( Site 1302)

Brussels, Bruxelles-Capitale, Region de, 1070, Belgium

Location

UZ Leuven ( Site 1301)

Leuven, Vlaams-Brabant, 3000, Belgium

Location

Clinica Cardio VID ( Site 0504)

Medellín, Antioquia, 050034, Colombia

Location

Ciensalud Ips S A S ( Site 0508)

Barranquilla, Atlántico, 080001, Colombia

Location

Fundación Valle del Lili ( Site 0509)

Cali, Valle del Cauca Department, 760032, Colombia

Location

Centro de Investigaciones Clinicas SAS ( Site 0505)

Cali, Valle del Cauca Department, 760036, Colombia

Location

C.H.U Hôpital Nord ( Site 1503)

Marseille, Bouches-du-Rhone, 13915, France

Location

Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois ( Site 1502)

Vandœuvre-lès-Nancy, Lorraine, 54511, France

Location

CHU Angers ( Site 1506)

Angers, Maine-et-Loire, 49933, France

Location

Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre-Pneumologie ( Site 1501)

Le Kremlin-Bicêtre, Paris, 94270, France

Location

Centre Hospitalier Universitaire de Poitiers ( Site 1505)

Poitiers, Vienne, 86021, France

Location

Thoraxklinik-Heidelberg gGmbH-Zentrum für Pulmonale Hypertonie ( Site 1603)

Heidelberg, Baden-Wurttemberg, 69126, Germany

Location

UKGM Gießen/Marburg ( Site 1604)

Giessen, Hesse, 35392, Germany

Location

Medizinische Hochschule Hannover ( Site 1602)

Hanover, Lower Saxony, 30625, Germany

Location

Universitaetsklinikum Carl Gustav Carus Dresden ( Site 1601)

Dresden, Saxony, 01307, Germany

Location

Universitätsklinikum Schleswig-Holstein-Pneumologie ( Site 1605)

Lübeck, Schleswig-Holstein, 23538, Germany

Location

Unidad De Diagnostico Cardiologico-Unidad de Diagnostico Cardiologico ( Site 0605)

Guatemala City, 01001, Guatemala

Location

MEDI-K ( Site 0607)

Guatemala City, 01009, Guatemala

Location

Clinica Medica ( Site 0601)

Guatemala City, 01010, Guatemala

Location

Private Practice - Dr. Jeremias Guerra Mejia ( Site 0603)

Guatemala City, 01010, Guatemala

Location

Rambam Health Care Campus ( Site 1701)

Haifa, 3109601, Israel

Location

Rabin Medical Center ( Site 1702)

Petah Tikva, 4941 492, Israel

Location

Cattinara Hospital ( Site 1801)

Trieste, Friuli Venezia Giulia, 34149, Italy

Location

Ospedale San Gerardo-ASST Monza-Cardio Vasolare- Clinica pneumologica ( Site 1802)

Monza, Lombardy, 20900, Italy

Location

ISMETT Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione ( Site 1804)

Palermo, 90127, Italy

Location

Centro Médico Nacional Siglo XXI ( Site 0708)

Mexico City, Mexico City, 06760, Mexico

Location

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0704)

Mexico City, Mexico City, 14080, Mexico

Location

INVECORDIS S.C. ( Site 0703)

Hacienda de Las Palmas, State of Mexico, 52787, Mexico

Location

Instituto Nacional de Cardiologia Ignacio Chavez ( Site 0701)

México, 14080, Mexico

Location

Unidad de Investigacon de la Clinica Internacional ( Site 0804)

Lima Cercado, Lima region, 15001, Peru

Location

Clinica Ricardo Palma-Centro de Investigacion de Enfermedades Respiratorias Thorax ( Site 0806)

San Isidro, Lima region, 15036, Peru

Location

Clínica Providencia ( Site 0803)

San Miguel, Lima region, 15088, Peru

Location

Charlotte Maxeke Johannesburg Academic Hospital ( Site 2108)

Johannesburg, Gauteng, 2193, South Africa

Location

Netcare Milpark Hospital ( Site 2103)

Johannesburg, Gauteng, 2193, South Africa

Location

Netcare St Augustine's Hospital ( Site 2105)

Durban, KwaZulu-Natal, 4001, South Africa

Location

TREAD Research ( Site 2101)

Cape Town, Western Cape, 7500, South Africa

Location

Gachon University Gil Medical Center ( Site 1101)

Namdong-gu, Incheon, 21565, South Korea

Location

Seoul National University Hospital ( Site 1103)

Seoul, 03080, South Korea

Location

Asan Medical Center ( Site 1102)

Seoul, 05505, South Korea

Location

Samsung Medical Center ( Site 1104)

Seoul, 06355, South Korea

Location

Hospital Universitario Marqués de Valdecilla-Pneumology ( Site 2003)

Santander, Cantabria, 39008, Spain

Location

HOSPITAL CLÍNIC DE BARCELONA ( Site 2001)

Barcelona, Catalonia, 08036, Spain

Location

Parc de Salut Mar - Hospital del Mar ( Site 2006)

Barcelona, 08003, Spain

Location

Hospital Universitari Vall d'Hebron ( Site 2002)

Barcelona, 08035, Spain

Location

HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO ( Site 2005)

Seville, 41013, Spain

Location

University Hospital Basel ( Site 2205)

Basel, Canton of Basel-City, 4031, Switzerland

Location

UniversitätsSpital Zürich ( Site 2201)

Zurich, Canton of Zurich, 8091, Switzerland

Location

Cantonal Hospital St.Gallen ( Site 2203)

Sankt Gallen, 9007, Switzerland

Location

Hacettepe Universite Hastaneleri ( Site 2301)

Ankara, 06230, Turkey (Türkiye)

Location

Ankara Bilkent Şehir Hastanesi. ( Site 2307)

Ankara, 06800, Turkey (Türkiye)

Location

Ankara University Health Practice and Research Hospitals ( Site 2310)

Ankara, 6100, Turkey (Türkiye)

Location

Eskisehir Osmangazi University-Cardiology ( Site 2304)

Eskişehir, 26480, Turkey (Türkiye)

Location

Istanbul Universitesi Istanbul Tıp Fakultesi Hastanesi-Chest Disease ( Site 2302)

Istanbul, 34093, Turkey (Türkiye)

Location

Hammersmith Hospital-Department of Cardiology ( Site 2401)

London, London, City of, W12 OHS, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust-Clinical Research Facility ( Site 2405)

Sheffield, S10 2JF, United Kingdom

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Hypertension, Pulmonary; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Lung Diseases, Obstructive; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2022
• First Posted: November 10, 2022
• Study Start: March 16, 2023
• Primary Completion: April 9, 2026
• Study Completion (Estimated): October 8, 2029
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

AR (5); US (18); CO (4); DE (5); ME (4); KR (4); ES (5); CH (3); BE (2); IL (2); ZA (4); AU (2); TU (5); IT (3); FR (5); GU (4); PE (3); GB (2)