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

Chronic Obstructive Pulmonary Disease Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05612035
• Other study ID #: 5475-013
• Secondary ID: MK-5475-0132022-
• Status: Recruiting
• Phase: Phase 2
• Start date: March 16, 2023
• Est. completion date: March 23, 2028

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 85 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: March 23, 2028
• Est. primary completion date: April 7, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Hypertension
• Hypertension, Pulmonary
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive
• Pulmonary Hypertension

Intervention

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

Locations

Country	Name	City	State
Argentina	Fundación Respirar ( Site 0305)	Buenos Aires
Argentina	Hospital Privado Universitario de Córdoba-Clinical Cardiology Department ( Site 0302)	Cordoba
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
Australia	The Prince Charles Hospital ( Site 0904)	Brisbane	Queensland
Australia	Mater Misericordiae Limited ( Site 0905)	South Brisbane	Queensland
Australia	Westmead Hospital-Department of Respiratory and Sleep Medicine ( Site 0902)	Westmead	New South Wales
Austria	Medizinische Universität Graz-Klinische Abteilung für Pulmonologie ( Site 1201)	Graz	Steiermark
Austria	Medizinische Universitaet Innsbruck ( Site 1202)	Innsbruck	Tirol
Belgium	Université Libre de Bruxelles - Hôpital Erasme ( Site 1302)	Brussels	Bruxelles-Capitale, Region De
Colombia	Ciensalud Ips S A S ( Site 0508)	Barranquilla	Atlantico
Colombia	Centro de Investigaciones Clinicas SAS ( Site 0505)	Cali	Valle Del Cauca
Colombia	Fundación Valle del Lili ( Site 0509)	Cali	Valle Del Cauca
Colombia	Clinica Cardio VID ( Site 0504)	Medellín	Antioquia
France	Hôpitaux Universitaires Paris Sud - Hôpital Bicêtre-Pneumologie ( Site 1501)	Le Kremlin-Bicêtre	Paris
France	C.H.U Hôpital Nord ( Site 1503)	Marseille	Bouches-du-Rhone
France	Centre Hospitalier Universitaire de Poitiers ( Site 1505)	Poitiers	Vienne
Germany	Universitaetsklinikum Carl Gustav Carus Dresden ( Site 1601)	Dresden	Sachsen
Germany	UKGM Gießen/Marburg ( Site 1604)	Gießen	Hessen
Germany	Medizinische Hochschule Hannover ( Site 1602)	Hannover	Niedersachsen
Germany	Thoraxklinik-Heidelberg gGmbH-Zentrum für Pulmonale Hypertonie ( Site 1603)	Heidelberg	Baden-Wurttemberg
Germany	Universitätsklinikum Schleswig-Holstein-Pneumologie ( Site 1605)	Lübeck	Schleswig-Holstein
Israel	Rambam Health Care Campus ( Site 1701)	Haifa
Israel	Rabin Medical Center ( Site 1702)	Petah Tikva
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	Cattinara Hospital ( Site 1801)	Trieste	Friuli-Venezia Giulia
Korea, Republic of	Gachon University Gil Medical Center ( Site 1101)	Namdong-gu	Incheon
Korea, Republic of	Asan Medical Center ( Site 1102)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 1103)	Seoul
Mexico	Instituto Nacional de Cardiologia Ignacio Chavez ( Site 0701)	Mexico
Peru	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
South Africa	TREAD Research ( Site 2101)	Cape Town	Western Cape
South Africa	Netcare St Augustine's Hospital ( Site 2105)	Durban	Kwazulu-Natal
South Africa	Netcare Milpark Hospital ( Site 2103)	Johannesburg	Gauteng
Spain	HOSPITAL CLÍNIC DE BARCELONA ( Site 2001)	Barcelona	Cataluna
Spain	Hospital Universitari Vall d'Hebron ( Site 2002)	Barcelona	Cataluna
Spain	Parc de Salut Mar - Hospital del Mar ( Site 2006)	Barcelona
Spain	Hospital Universitario Marqués de Valdecilla-Pneumology ( Site 2003)	Santander	Cantabria
Spain	HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO ( Site 2005)	Sevilla
Switzerland	Cantonal Hospital St.Gallen ( Site 2203)	Sankt Gallen
Switzerland	UniversitätsSpital Zürich ( Site 2201)	Zürich	Zurich
Turkey	Ankara Bilkent Sehir Hastanesi. ( Site 2307)	Ankara
Turkey	Hacettepe Universite Hastaneleri ( Site 2301)	Ankara
Turkey	Eskisehir Osmangazi University-Cardiology ( Site 2304)	Eskisehir
Turkey	Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi-Chest Disease ( Site 2302)	Istanbul
United Kingdom	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 States	University of Colorado Anschutz Medical Campus-University of Colorado Hospital Cardiac and Vascular	Aurora	Colorado
United States	University of Virginia Health System-Division of Pulmonary and Critical Care Medicine ( Site 0111)	Charlottesville	Virginia
United States	UT Southwestern Medical Center ( Site 0114)	Dallas	Texas
United States	Alexian Brothers Medical Center-Pulmonary ( Site 0109)	Elk Grove Village	Illinois
United States	Corewell Health ( Site 0133)	Grand Rapids	Michigan
United States	The University of Texas Health Science Center at Houston ( Site 0105)	Houston	Texas
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	Intermountain Medical Center-Division of Pulmonary & Critical Care Medicine ( Site 0140)	Murray	Utah
United States	Creighton University Clinical Research Office ( Site 0123)	Omaha	Nebraska
United States	Temple University Hospital ( Site 0104)	Philadelphia	Pennsylvania
United States	Mayo Clinic in Rochester, Minnesota ( Site 0131)	Rochester	Minnesota
United States	Clinovation Intl. Corp. ( Site 0108)	Sebring	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Colombia,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Mexico,  Peru,  South Africa,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Mean Change From Baseline in 6MWD at Week 12	6MWD is assessed using the 6-minute walk test (6MWT).	Baseline and Week 12
Secondary	Mean Change From Baseline in N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) at Week 12	NT-proBNP was measured at baseline and Week 12.	Baseline and Week 12
Secondary	Mean Change From Baseline in NT-ProBNP at Week 24	NT-proBNP was measured at baseline and Week 24	Baseline and Week 24
Secondary	Percentage of Participants Whose World Health Organization-Functional Class (WHO-FC) Does not Worsen Relative to Baseline at 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
Secondary	Percentage of Participants Whose WHO-FC Does not Worsen Relative to Baseline at 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
Secondary	Percentage of Participants With One or More Adverse Events (AEs)	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 104
Secondary	Percentage of Participants who Discontinued Study Treatment due to an AE	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 102

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary