A Study of the Efficacy and Safety of MK-5475 in Participants With Pulmonary Arterial Hypertension (INSIGNIA-PAH: Phase 2/3 Study of an Inhaled sGC Stimulator in PAH) (MK-5475-007)
Pulmonary Arterial Hypertension, Hypertension, Pulmonary
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension
Eligibility Criteria
Inclusion Criteria:
Pulmonary arterial hypertension (PAH) in one of the following groups:
- Idiopathic PAH
- Heritable PAH
- Drug and toxin-induced PAH
- PAH associated with connective tissue disease, HIV infection, or congenital heart disease.
- Diagnosis of PAH documented by right heart catheterization (RHC).
Eligibility RHC meeting all of the following criteria:
- Mean pulmonary artery pressure (mPAP) ≥25 mmHg
- Pulmonary vascular resistance (PVR) of ≥3 Wood units
- Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) ≤15 mmHg.
- World Health Organization functional class (WHO-FC) symptoms between Class II and IV.
- Two 6-Minute walk distance (6MWD) measurements between 150 and 500 meters, one at screening and one at randomization.
- Stable concomitant background PAH-specific therapy.
- Body Mass Index (BMI) between 18.5 kg/m² and 40 kg/m² .
- Agree to be abstinent from heterosexual intercourse or use contraception during the intervention period and for at least 14 days after the last dose of study intervention.
- Female participants may not be pregnant or breastfeeding.
Exclusion Criteria:
- Group 2 to 5 pulmonary hypertension.
PAH in one of the following groups:
- Long term responders to calcium channel blockers
- Overt features of venous/capillary involvement
- Evidence of more-than-mild obstructive lung disease.
- Evidence of more-than-mild parenchymal lung disease.
- Evidence of more-than-mild obstructive sleep apnea (OSA) that is untreated.
Evidence or history of left heart disease, including any of the following:
- Left ventricular ejection fraction (LVEF) ≤45%
- Moderate or severe left-sided valvular disease (aortic or mitral valve stenosis or regurgitation)
- Significant left ventricular diastolic dysfunction on echocardiographic evaluation
- Presence of 3 or more of the following risk factors for heart failure with preserved ejection fraction: BMI>30 kg/m², essential systemic hypertension, diabetes mellitus of any type, or coronary artery disease.
- Oxygen saturation measured by pulse oximetry (SpO₂) <90%, despite supplemental oxygen therapy.
- Chronic renal insufficiency (eGFR <30 mL/min)
- Chronic liver disease (i.e., Child-Pugh B or C), portal hypertension, cirrhosis, or significant hepatic laboratory abnormalities.
- Current smoker or currently uses electronic cigarettes (vapes).
- History of cancer, except: nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies which have been successfully treated, with appropriate follow up, and unlikely to recur for the duration of the study.
Sites / Locations
- University of California San Diego Health-Pulmonary Critical Care ( Site 0061)Recruiting
- University of California Davis Health-Internal Medicine: Pulmonary, Critical Care and Sleep MedicineRecruiting
- UCSF Helen Diller Medical Center at Parnassus Heights ( Site 0063)Recruiting
- University of Colorado - Denver ( Site 0003)Recruiting
- Cardiovascular Institute of North Colorado - Banner Health ( Site 0013)
- Georgetown University Hospital ( Site 0025)
- University of Miami Hospital-Division of Pulmonary & Critical Care ( Site 0053)Recruiting
- AdventHealth Orlando ( Site 0040)Recruiting
- Tampa General Hospital ( Site 0058)Recruiting
- Indiana University Health Methodist Hospital ( Site 0045)Recruiting
- University of Iowa Hospital and Clinics ( Site 0009)
- University of Kansas Medical Center ( Site 0038)Recruiting
- University of Kentucky ( Site 0006)Recruiting
- Norton Pulmonary Specialists ( Site 0048)Recruiting
- University of Maryland ( Site 0032)Recruiting
- Washington University School of Medicine ( Site 0066)Recruiting
- University of Nebraska Medical Center ( Site 0041)Recruiting
- University of New Mexico, Health Sciences Center ( Site 0028)Recruiting
- Clinical Trials Unit at Eastowne Medical Office Building ( Site 0019)Recruiting
- AnMed Health ( Site 0033)
- Statcare Pulmonary Consultants ( Site 0067)Recruiting
- University of Texas Southwestern Medical Center at Dallas ( Site 0012)
- Houston Methodist Research Institute ( Site 0036)Recruiting
- The University of Texas Health Science Center at Houston ( Site 0054)Recruiting
- Sentara Norfolk General Hospital ( Site 0014)
- West Virginia University-WVU Heart and Vascular Institute ( Site 0051)Recruiting
- Cardiologia Palermo ( Site 0140)Recruiting
- Hospital El Cruce Nestor Carlos Kirchner ( Site 0132)Recruiting
- Centro Medico Capital ( Site 0131)Recruiting
- Hospital Universitario Austral ( Site 0138)Recruiting
- Instituto de Investigaciones Clinicas Quilmes ( Site 0141)
- Sanatorio de la Trinidad Mitre ( Site 0130)Recruiting
- Instituto Cardiovascular de Rosario ( Site 0128)Recruiting
- Hospital Privado Universitario de Córdoba ( Site 0137)Recruiting
- Nepean Hospital ( Site 0184)Recruiting
- Macquarie University ( Site 0180)Recruiting
- John Hunter Hospital ( Site 0185)Recruiting
- UZ Leuven ( Site 0600)Recruiting
- Peter Lougheed Centre ( Site 0107)Recruiting
- University Health Network - Toronto General Hospital ( Site 0104)Recruiting
- IUCPQ ( Site 0111)Recruiting
- Centro Cardiovascular Colombiano Clínica Santa María ( Site 0154)Recruiting
- Hospital Universitario San Ignacio ( Site 0152)Recruiting
- Fundacion Cardiovascular de Colombia ( Site 0155)Recruiting
- CHRU Brest - Hopital Cavale Blanche ( Site 0254)Recruiting
- CHU de Toulouse - Hopital Larrey ( Site 0258)Recruiting
- Institut Coeur Poumon - CHRU de Lille ( Site 0252)Recruiting
- Centre Hospitalier Universitaire de Rouen ( Site 0253)Recruiting
- CHU - Hopital de Bicetre ( Site 0251)Recruiting
- Thoraxklinik Heidelberg gGmbH am Universitaetsklinikum Heidelberg ( Site 0276)Recruiting
- Klinikum Würzburg Mitte-Medizinische Klinik - Schwerpunkt Pneumologie & Beatmungsmedizin ( Site 0280Recruiting
- Universitaetsklinikum Giessen und Marburg GmbH ( Site 0279)Recruiting
- Medizinische Hochschule Hannover ( Site 0284)Recruiting
- Uniklinikum Dresden ( Site 0283)Recruiting
- Universitaetsklinikum Leipzig ( Site 0285)Recruiting
- AHEPA University General Hospital of Thessaloniki ( Site 0577)Recruiting
- Soroka Medical Center ( Site 0330)Recruiting
- Rambam Medical Center ( Site 0335)Recruiting
- Wolfson Medical Center [Holon, Israel] ( Site 0333)
- Shaare Zedek Medical Center ( Site 0331)Recruiting
- Rabin Medical Center ( Site 0327)Recruiting
- University of Naples Federico II ( Site 0308)Recruiting
- Azienda Ospedaliera Policlinico Umberto I ( Site 0301)Recruiting
- Ospedale San Gerardo - ASST Monza ( Site 0304)Recruiting
- Centro Cardiologico Monzino IRCCS ( Site 0306)Recruiting
- Fondazione IRCCS Policlinico San Matteo ( Site 0302)Recruiting
- Consultorio 1020 Hospital Angeles Xalapa ( Site 0654)Recruiting
- Operadora de Hospitales Angeles. S.A. de C.V. -Sucursal Lomas ( Site 0653)Recruiting
- Instituto Nacional de Cardiología -Ignacio Chavez ( Site 0651)Recruiting
- Christchurch Hospital ( Site 0201)Recruiting
- Greenlane Clinical Centre ( Site 0203)Recruiting
- Specjalistyczny Szpital im. Dr Alfreda Sokolowskiego w Walbrzychu ( Site 0351)Recruiting
- Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie ( Site 0352)Recruiting
- Krakowski Szpital Specjalistyczny im. Jana Pawa II-Oddzial Kliniczny Chorob Serca i Naczyn z PododdRecruiting
- Scientific Research Institute Complex Problems Cardiovascular Disease ( Site 0403)
- Almazov National Medical Research Centre of the Ministry of Health ( Site 0402)
- Akademiska sjukhuset ( Site 0453)Recruiting
- Sahlgrenska Universitetssjukhuset-Cardiology Research Unit ( Site 0452)Recruiting
- Ege Universitesi Hastanesi-Cardilogy Department ( Site 0504)Recruiting
- Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 0510)Recruiting
- Akdeniz Uni.Tip Fakultesi Saglik Uygulama ve Arastirma Merkezi ( Site 0508)Recruiting
- Eskisehir Osmangazi Uni. Tip Fakultesi Hastanesi ( Site 0506)Recruiting
- Istanbul Uni. Kardiyoloji Enstitusu ( Site 0502)Recruiting
- Istanbul Universitesi Istanbul Tip Fakultesi ( Site 0509)Recruiting
- Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 0501)Recruiting
- Dokuz Eylul University Faculty of Medicine ( Site 0505)Recruiting
- Golden Jubilee National Hospital ( Site 0556)Recruiting
- Royal Brompton and Harefield NHS Trust ( Site 0553)Recruiting
- Imperial College Healthcare NHS Trust - Hammersmith Hospital ( Site 0554)Recruiting
- The Freeman Hosp.Newcastle upon Tyne Hosp NHS Trust ( Site 0552)Recruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Phase 2 Cohort MK-5475 380 µg
Phase 2 Cohort MK-5475 100 µg
Phase 2 Cohort MK-5475 32 µg
Phase 2 Cohort Placebo
Phase 3 Cohort MK-5475
Phase 3 Cohort Placebo
Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period and for optional 24 month extension period.
Participants receive MK-5475 100 µg via oral inhalation once daily for 12 week base period and for optional 24 month extension period.
Participants receive MK-5475 32 µg via oral inhalation once daily for 12 week base period and for optional 24 month extension period.
Participants receive placebo via oral inhalation once daily for 12 week base period, and one of the MK-5475 doses (380, 100, or 32 µg) for the optional 24 month extension period.
Participants receive one of 3 MK-5475 doses (380, 100 or 32 µg) to be selected at end of the Phase 2 Cohort, administered via oral inhalation once daily for 12-week base period and up to 60 months in the extension period
Participants receive placebo via oral inhalation once daily for 12 week base period and up to 60 months in the extension period.