Clinical trial NCT05612035: Frespaciguat (MK-5475) INSIGNIA-PH-COPD: A Study of the Efficacy and Safety of Frespaciguat (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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pulmonary Hypertension
Chronic Obstructive Pulmonary Disease
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-11-10
Enrollment: 120
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Mean Change From Baseline in 6-minute Walk Distance (6MWD) at Week 24
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Mean Change From Baseline in 6MWD at Week 12
timeFrame: Baseline and Week 12
measure: Mean Change From Baseline in N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) at Week 12
timeFrame: Baseline and Week 12
measure: Mean Change From Baseline in NT-ProBNP at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants Whose World Health Organization-Functional Class (WHO-FC) Does not Worsen Relative to Baseline at Week 12
timeFrame: Baseline and Week 12
measure: Percentage of Participants Whose WHO-FC Does not Worsen Relative to Baseline at Week 24
timeFrame: Baseline and Week 24
measure: Percentage of Participants With One or More Adverse Events (AEs)
timeFrame: Up to Week 206
measure: Percentage of Participants who Discontinued Study Treatment due to an AE
timeFrame: Up to Week 204
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Medical Center at Parnassus Heights ( Site 0110)
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus-University of Colorado Hospital Cardiac and Vascular ( Site 0101)
state: Colorado
city: Sebring
country: United States
facility: Clinovation Intl. Corp. ( Site 0108)
state: Florida
city: Elk Grove Village
country: United States
facility: Alexian Brothers Medical Center-Pulmonary ( Site 0109)
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa ( Site 0103)
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center-IM-Pulmonary and Critical Care Medicine ( Site 0102)
state: Kansas
city: Lexington
country: United States
facility: Lexington VA Medical Center - Cooper Division ( Site 0137)
state: Kentucky
city: Grand Rapids
country: United States
facility: Corewell Health ( Site 0133)
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic in Rochester, Minnesota ( Site 0131)
state: Minnesota
city: Omaha
country: United States
facility: Creighton University Clinical Research Office ( Site 0123)
state: Nebraska
city: Albuquerque
country: United States
facility: University of New Mexico Hospital ( Site 0146)
state: New Mexico
city: Chapel Hill
country: United States
facility: UNC Health - Eastowne Medical Office-Clinical Trials Unit ( Site 0147)
state: North Carolina
city: Philadelphia
country: United States
facility: Temple University Hospital ( Site 0104)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Montefiore University Hospital-Department of Medicine ( Site 0149)
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center ( Site 0114)
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston ( Site 0105)
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center-Division of Pulmonary & Critical Care Medicine ( Site 0140)
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System-Division of Pulmonary and Critical Care Medicine ( Site 0111)
state: Virginia
city: Caba
country: Argentina
facility: Fundación Respirar ( Site 0305)
state: Buenos Aires
city: La PLata
country: Argentina
facility: Centro Medico Capital ( Site 0301)
state: Buenos Aires
city: San Miguel de Tucumán
country: Argentina
facility: Instituto de Cardiologia de Tucuman-Area de Investigacion Clinica ( Site 0303)
state: Tucuman
city: Caba
country: Argentina
facility: Hospital Britanico de Buenos Aires ( Site 0307)
city: Cordoba
country: Argentina
facility: Hospital Privado Universitario de Córdoba-Clinical Cardiology Department ( Site 0302)
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital-Department of Respiratory Medicine ( Site 0903)
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital ( Site 0902)
state: New South Wales
city: Auchenflower
country: Australia
facility: WESLEY RESEARCH INSTITUTE Limited ( Site 0906)
state: Queensland
city: Brisbane
country: Australia
facility: The Prince Charles Hospital ( Site 0904)
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Misericordiae Limited ( Site 0905)
state: Queensland
city: Graz
country: Austria
facility: Medizinische Universität Graz-Klinische Abteilung für Pulmonologie ( Site 1201)
state: Steiermark
city: Innsbruck
country: Austria
facility: Medizinische Universitaet Innsbruck ( Site 1202)
state: Tirol
city: Brussels
country: Belgium
facility: Université Libre de Bruxelles - Hôpital Erasme ( Site 1302)
state: Bruxelles-Capitale, Region De
city: Leuven
country: Belgium
facility: UZ Leuven ( Site 1301)
state: Vlaams-Brabant
city: Medellín
country: Colombia
facility: Clinica Cardio VID ( Site 0504)
state: Antioquia
city: Barranquilla
country: Colombia
facility: Ciensalud Ips S A S ( Site 0508)
state: Atlantico
city: Cali
country: Colombia
facility: Fundación Valle del Lili ( Site 0509)
state: Valle Del Cauca
city: Cali
country: Colombia
facility: Centro de Investigaciones Clinicas SAS ( Site 0505)
state: Valle Del Cauca
city: Marseille
country: France
facility: C.H.U Hôpital Nord ( Site 1503)
state: Bouches-du-Rhone
city: Vandoeuvre lès Nancy
country: France
facility: Centre Hospitalier Régional Universitaire de Nancy - Hôpitaux de Brabois ( Site 1502)
state: Lorraine
city: Angers
country: France
facility: CHU Angers ( Site 1506)
state: Maine-et-Loire
city: Le Kremlin-Bicêtre
country: France
facility: Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre-Pneumologie ( Site 1501)
state: Paris
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers ( Site 1505)
state: Vienne
city: Heidelberg
country: Germany
facility: Thoraxklinik-Heidelberg gGmbH-Zentrum für Pulmonale Hypertonie ( Site 1603)
state: Baden-Wurttemberg
city: Gießen
country: Germany
facility: UKGM Gießen/Marburg ( Site 1604)
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover ( Site 1602)
state: Niedersachsen
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus Dresden ( Site 1601)
state: Sachsen
city: Luebeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein-Pneumologie ( Site 1605)
state: Schleswig-Holstein
city: Guatemala City
country: Guatemala
facility: Unidad De Diagnostico Cardiologico-Unidad de Diagnostico Cardiologico ( Site 0605)
city: Guatemala City
country: Guatemala
facility: Private Practice - Dr. Jeremias Guerra Mejia ( Site 0603)
city: Guatemala
country: Guatemala
facility: MEDI-K ( Site 0607)
city: Guatemala
country: Guatemala
facility: Clinica Medica ( Site 0601)
city: Haifa
country: Israel
facility: Rambam Health Care Campus ( Site 1701)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center ( Site 1702)
city: Trieste
country: Italy
facility: Cattinara Hospital ( Site 1801)
state: Friuli-Venezia Giulia
city: Monza
country: Italy
facility: Ospedale San Gerardo-ASST Monza-Cardio Vasolare- Clinica pneumologica ( Site 1802)
state: Lombardia
city: Palermo
country: Italy
facility: ISMETT Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione ( Site 1804)
city: Namdong-gu
country: Korea, Republic of
facility: Gachon University Gil Medical Center ( Site 1101)
state: Incheon
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 1103)
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center ( Site 1102)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 1104)
city: Mexico City
country: Mexico
facility: Centro Médico Nacional Siglo XXI ( Site 0708)
state: Distrito Federal
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0704)
state: Distrito Federal
city: Hacienda De Las Palmas
country: Mexico
facility: INVECORDIS S.C. ( Site 0703)
city: Mexico
country: Mexico
facility: Instituto Nacional de Cardiologia Ignacio Chavez ( Site 0701)
city: Cercado De Lima
country: Peru
facility: Unidad de Investigacon de la Clinica Internacional ( Site 0804)
state: Lima
city: San Isidro
country: Peru
facility: Clinica Ricardo Palma-Centro de Investigacion de Enfermedades Respiratorias Thorax ( Site 0806)
state: Lima
city: San Miguel
country: Peru
facility: Clínica Providencia ( Site 0803)
state: Lima
city: Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital ( Site 2108)
state: Gauteng
city: Johannesburg
country: South Africa
facility: Netcare Milpark Hospital ( Site 2103)
state: Gauteng
city: Durban
country: South Africa
facility: Netcare St Augustine's Hospital ( Site 2105)
state: Kwazulu-Natal
city: Cape Town
country: South Africa
facility: TREAD Research ( Site 2101)
state: Western Cape
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla-Pneumology ( Site 2003)
state: Cantabria
city: Barcelona
country: Spain
facility: HOSPITAL CLÍNIC DE BARCELONA ( Site 2001)
state: Cataluna
city: Barcelona
country: Spain
facility: Parc de Salut Mar - Hospital del Mar ( Site 2006)
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron ( Site 2002)
city: Sevilla
country: Spain
facility: HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO ( Site 2005)
city: Basel
country: Switzerland
facility: University Hospital Basel ( Site 2205)
state: Basel-Stadt
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich ( Site 2201)
state: Zurich
city: Sankt Gallen
country: Switzerland
facility: Cantonal Hospital St.Gallen ( Site 2203)
city: Ankara
country: Turkey
facility: Hacettepe Universite Hastaneleri ( Site 2301)
city: Ankara
country: Turkey
facility: Ankara Bilkent Şehir Hastanesi. ( Site 2307)
city: Eskisehir
country: Turkey
facility: Eskisehir Osmangazi University-Cardiology ( Site 2304)
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Istanbul Tıp Fakultesi Hastanesi-Chest Disease ( Site 2302)
city: London
country: United Kingdom
facility: Hammersmith Hospital-Department of Cardiology ( Site 2401)
state: London, City Of
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust-Clinical Research Facility ( Site 2405)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: