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)

April 5, 2024 updated by: Merck Sharp & Dohme LLC

A Phase 2/3, Multicenter, Randomized, Double-blind, Placebo-Controlled, Adaptive Design Study to Evaluate the Efficacy and Safety of MK-5475 in Adults With Pulmonary Arterial Hypertension

This is a two-part (Phase 2/Phase 3) study of MK-5475, an inhaled soluble guanylate cyclase stimulator, in participants with pulmonary arterial hypertension (PAH).

The first part (Phase 2) will assess three different doses of MK-5475 compared to placebo in a base period of 12 weeks, followed by comparison of three different doses of MK-5475 during an optional 24 month extension period. The treatment dose with the best efficacy and safety profile in the phase 2 cohort base period will be selected for use in the second part (Phase 3) of the study. The primary hypothesis of Phase 2 is that at least one MK-5475 dose is superior to placebo in reducing pulmonary vascular resistance (PVR) from baseline at week 12.

The purpose of the second part (Phase 3) of the study is to confirm the efficacy, safety, and tolerability of MK-5475 at the selected dose compared to placebo during a 12 week base period followed by an extension period of up to 5 years. The primary hypothesis of Phase 3 is that MK-5475 is superior to placebo in increasing 6-minute walk distance (6MWD) from baseline at week 12.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

450

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Argentina
      • Cordoba, Argentina, X5016KEH
        • Recruiting
        • Hospital Privado Universitario de Córdoba ( Site 0137)
        • Contact:
          • Study Coordinator
          • Phone Number: +54 351 468-8200
    • Buenos Aires
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1425BNG
        • Recruiting
        • Cardiologia Palermo ( Site 0140)
        • Contact:
          • Study Coordinator
          • Phone Number: 541136606676
      • Florencio Varela, Buenos Aires, Argentina, 1888
        • Recruiting
        • Hospital El Cruce Nestor Carlos Kirchner ( Site 0132)
        • Contact:
          • Study Coordinator
          • Phone Number: +5491158230726
      • La Plata, Buenos Aires, Argentina, B1904AAW
        • Recruiting
        • Centro Medico Capital ( Site 0131)
        • Contact:
          • Study Coordinator
          • Phone Number: +5492215317279
      • Pilar, Buenos Aires, Argentina, B1629ODT
        • Recruiting
        • Hospital Universitario Austral ( Site 0138)
        • Contact:
          • Study Coordinator
          • Phone Number: +54 230 448-2000
      • Quilmes, Buenos Aires, Argentina, B1878GEG
        • Active, not recruiting
        • Instituto de Investigaciones Clinicas Quilmes ( Site 0141)
    • Caba
      • Buenos Aires, Caba, Argentina, 1039
        • Recruiting
        • Sanatorio de la Trinidad Mitre ( Site 0130)
        • Contact:
          • Study Coordinator
          • Phone Number: +5491144799366
    • Santa Fe
      • Rosario, Santa Fe, Argentina, S2000DSR
        • Recruiting
        • Instituto Cardiovascular de Rosario ( Site 0128)
        • Contact:
          • Study Coordinator
          • Phone Number: +54 93416164246
  • Australia
    • New South Wales
      • Kingswood, New South Wales, Australia, 2747
        • Recruiting
        • Nepean Hospital ( Site 0184)
        • Contact:
          • Study Coordinator
          • Phone Number: +61247342000
      • Macquarie University, New South Wales, Australia, 2109
        • Recruiting
        • Macquarie University ( Site 0180)
        • Contact:
          • Study Coordinator
          • Phone Number: +61294226000
      • Newcastle, New South Wales, Australia, 2305
        • Recruiting
        • John Hunter Hospital ( Site 0185)
        • Contact:
          • Study Coordinator
          • Phone Number: 0249214440
  • Belgium
    • Bruxelles-Capitale, Region De
      • Brussels, Bruxelles-Capitale, Region De, Belgium, 1070
        • Recruiting
        • Université Libre de Bruxelles - Hôpital Erasme ( Site 0601)
        • Contact:
          • Study Coordinator
          • Phone Number: +32 (0) 2 555 56 02
    • Vlaams-Brabant
      • Leuven, Vlaams-Brabant, Belgium, 3000
        • Recruiting
        • UZ Leuven ( Site 0600)
        • Contact:
          • Study Coordinator
          • Phone Number: 3216346833
  • Canada
      • Quebec, Canada, G1V 4G5
        • Recruiting
        • IUCPQ ( Site 0111)
        • Contact:
          • Study Coordinator
          • Phone Number: 41865687112449
    • Alberta
      • Calgary, Alberta, Canada, T1Y 6J4
        • Recruiting
        • Peter Lougheed Centre ( Site 0107)
        • Contact:
          • Study Coordinator
          • Phone Number: 4038305456
    • Ontario
      • Toronto, Ontario, Canada, M5G 2N2
        • Recruiting
        • University Health Network - Toronto General Hospital ( Site 0104)
        • Contact:
          • Study Coordinator
          • Phone Number: 416-340-4485
  • Colombia
    • Antioquia
      • Medellín, Antioquia, Colombia, 050034
        • Completed
        • Centro Cardiovascular Colombiano Clínica Santa María ( Site 0154)
    • Distrito Capital De Bogota
      • Bogota, Distrito Capital De Bogota, Colombia, 110231
        • Recruiting
        • Hospital Universitario San Ignacio ( Site 0152)
        • Contact:
          • Study Coordinator
          • Phone Number: +5712882284
    • Santander
      • Piedecuesta, Santander, Colombia, 681017
        • Recruiting
        • Fundacion Cardiovascular de Colombia ( Site 0155)
        • Contact:
          • Study Coordinator
          • Phone Number: +573175741421
  • France
    • Finistere
      • Brest, Finistere, France, 29609
        • Recruiting
        • CHRU Brest - Hopital Cavale Blanche ( Site 0254)
        • Contact:
          • Study Coordinator
          • Phone Number: +33298223333
    • Haute-Garonne
      • Toulouse, Haute-Garonne, France, 31059
        • Recruiting
        • CHU de Toulouse - Hopital Larrey ( Site 0258)
        • Contact:
          • Study Coordinator
          • Phone Number: +33556795679
    • Nord-Pas-de-Calais
      • Lille Cedex, Nord-Pas-de-Calais, France, 59037
        • Recruiting
        • Institut Coeur Poumon - CHRU de Lille ( Site 0252)
        • Contact:
          • Study Coordinator
          • Phone Number: 33320445721
    • Seine-Maritime
      • Rouen, Seine-Maritime, France, 76031
        • Recruiting
        • Centre Hospitalier Universitaire de Rouen ( Site 0253)
        • Contact:
          • Study Coordinator
          • Phone Number: +33232885406
    • Val-de-Marne
      • Le Kremlin-Bicetre, Val-de-Marne, France, 94275
        • Recruiting
        • CHU - Hopital de Bicetre ( Site 0251)
        • Contact:
          • Study Coordinator
          • Phone Number: +33145212121
  • Germany
    • Baden-Wurttemberg
      • Heidelberg, Baden-Wurttemberg, Germany, 69126
        • Recruiting
        • Thoraxklinik Heidelberg gGmbH am Universitaetsklinikum Heidelberg ( Site 0276)
        • Contact:
          • Study Coordinator
          • Phone Number: +49 6221 396-8076
    • Bayern
      • Wuerzburg, Bayern, Germany, 97074
        • Recruiting
        • Klinikum Würzburg Mitte-Medizinische Klinik - Schwerpunkt Pneumologie & Beatmungsmedizin ( Site 0280
        • Contact:
          • Study Coordinator
          • Phone Number: 00499317910
    • Hessen
      • Gießen, Hessen, Germany, 35392
        • Recruiting
        • UKGM Gießen/Marburg ( Site 0279)
        • Contact:
          • Study Coordinator
          • Phone Number: +4964198560
    • Niedersachsen
      • Hannover, Niedersachsen, Germany, 30625
        • Recruiting
        • Medizinische Hochschule Hannover ( Site 0284)
        • Contact:
          • Study Coordinator
          • Phone Number: +49 511 532 3548
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
        • Recruiting
        • Uniklinikum Dresden ( Site 0283)
        • Contact:
          • Study Coordinator
          • Phone Number: +49 3513177238
      • Leipzig, Sachsen, Germany, 04103
        • Recruiting
        • Universitaetsklinikum Leipzig ( Site 0285)
        • Contact:
          • Study Coordinator
          • Phone Number: +493419716250
  • Greece
      • Thessaloniki, Greece, 54636
        • Active, not recruiting
        • AHEPA University General Hospital of Thessaloniki ( Site 0577)
  • Israel
      • Beer Sheva, Israel, 8410101
        • Recruiting
        • Soroka Medical Center ( Site 0330)
        • Contact:
          • Study Coordinator
          • Phone Number: +97286403832
      • Haifa, Israel, 3109601
        • Recruiting
        • Rambam Medical Center ( Site 0335)
        • Contact:
          • Study Coordinator
          • Phone Number: +97250206171
      • Holon, Israel, 5810000
        • Completed
        • Wolfson Medical Center [Holon, Israel] ( Site 0333)
      • Jerusalem, Israel, 9103102
        • Recruiting
        • Shaare Zedek Medical Center ( Site 0331)
        • Contact:
          • Study Coordinator
          • Phone Number: +972506865209
      • Petah Tikva, Israel, 4941492
        • Recruiting
        • Rabin Medical Center ( Site 0327)
        • Contact:
          • Study Coordinator
          • Phone Number: +97239377221
  • Italy
      • Milano, Italy, 20138
        • Recruiting
        • Centro Cardiologico Monzino IRCCS ( Site 0306)
        • Contact:
          • Study Coordinator
          • Phone Number: +390258002299
      • Pavia, Italy, 27100
        • Recruiting
        • Fondazione IRCCS Policlinico San Matteo ( Site 0302)
        • Contact:
          • Study Coordinator
          • Phone Number: +390382503460
    • Campania
      • Naples, Campania, Italy, 80100
        • Recruiting
        • University of Naples Federico II ( Site 0308)
        • Contact:
          • Study Coordinator
          • Phone Number: +390817462242
    • Lazio
      • Roma, Lazio, Italy, 00161
        • Recruiting
        • Azienda Ospedaliera Policlinico Umberto I ( Site 0301)
        • Contact:
          • Study Coordinator
          • Phone Number: +390649979016
    • Monza E Brianza
      • Monza, Monza E Brianza, Italy, 20900
        • Recruiting
        • Ospedale San Gerardo - ASST Monza ( Site 0304)
        • Contact:
          • Study Coordinator
          • Phone Number: +390392339245
  • Mexico
      • Huixquilucan, Mexico, 52763
        • Recruiting
        • Operadora de Hospitales Angeles. S.A. de C.V. -Sucursal Lomas ( Site 0653)
        • Contact:
          • Study Coordinator
          • Phone Number: +5552469709
      • Mexico D.F, Mexico, 14080
        • Recruiting
        • Instituto Nacional de Cardiología -Ignacio Chavez ( Site 0651)
        • Contact:
          • Study Coordinator
          • Phone Number: 5555732911
    • Veracruz
      • Xalapa, Veracruz, Mexico, 91193
        • Recruiting
        • Consultorio 1020 Hospital Angeles Xalapa ( Site 0654)
        • Contact:
          • Study Coordinator
          • Phone Number: +522281084321
  • New Zealand
      • Auckland, New Zealand, 1051
        • Completed
        • Greenlane Clinical Centre ( Site 0203)
    • Canterbury
      • Christchurch, Canterbury, New Zealand, 8011
        • Recruiting
        • Christchurch Hospital ( Site 0201)
        • Contact:
          • Study Coordinator
          • Phone Number: +64274677583
  • Poland
    • Dolnoslaskie
      • Walbrzych, Dolnoslaskie, Poland, 58-309
        • Recruiting
        • Specjalistyczny Szpital im. Dr Alfreda Sokolowskiego w Walbrzychu ( Site 0351)
        • Contact:
          • Study Coordinator
          • Phone Number: +48746489622
    • Lubelskie
      • Lublin, Lubelskie, Poland, 20-954
        • Recruiting
        • Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie ( Site 0352)
        • Contact:
          • Study Coordinator
          • Phone Number: 601366148
    • Malopolskie
      • Krakow, Malopolskie, Poland, 31-202
        • Recruiting
        • Krakowski Szpital Specjalistyczny im. Jana Pawa II-Oddzial Kliniczny Chorob Serca i Naczyn z Pododd
        • Contact:
          • Study Coordinator
          • Phone Number: +485000099734
  • Russian Federation
    • Kemerovskaya Oblast
      • Kemerovo, Kemerovskaya Oblast, Russian Federation, 650002
        • Completed
        • Scientific Research Institute Complex Problems Cardiovascular Disease ( Site 0403)
    • Sankt-Peterburg
      • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197341
        • Completed
        • Almazov National Medical Research Centre of the Ministry of Health ( Site 0402)
  • Sweden
    • Uppsala Lan
      • Uppsala, Uppsala Lan, Sweden, 751 85
        • Completed
        • Akademiska sjukhuset ( Site 0453)
    • Vastra Gotalands Lan
      • Gothenburg, Vastra Gotalands Lan, Sweden, 413 45
        • Recruiting
        • Sahlgrenska Universitetssjukhuset-Cardiology Research Unit ( Site 0452)
        • Contact:
          • Study Coordinator
          • Phone Number: +46313427557
  • Turkey
      • Ankara, Turkey, 06100
        • Recruiting
        • Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 0510)
        • Contact:
          • Study Coordinator
          • Phone Number: 903123055000
      • Antalya, Turkey, 07059
        • Recruiting
        • Akdeniz Uni.Tip Fakultesi Saglik Uygulama ve Arastirma Merkezi ( Site 0508)
        • Contact:
          • Study Coordinator
          • Phone Number: +902422496770
      • Eskisehir, Turkey, 26040
        • Recruiting
        • Eskisehir Osmangazi Uni. Tip Fakultesi Hastanesi ( Site 0506)
        • Contact:
          • Study Coordinator
          • Phone Number: +905332337849
      • Istanbul, Turkey, 34096
        • Recruiting
        • Istanbul Uni. Kardiyoloji Enstitusu ( Site 0502)
        • Contact:
          • Study Coordinator
          • Phone Number: +905322860797
      • Istanbul, Turkey, 34390
        • Recruiting
        • Istanbul Universitesi Istanbul Tip Fakultesi ( Site 0509)
        • Contact:
          • Study Coordinator
          • Phone Number: +905322831726
      • Istanbul, Turkey, 34899
        • Recruiting
        • Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 0501)
        • Contact:
          • Study Coordinator
          • Phone Number: +902166254545
      • Izmir, Turkey, 35330
        • Recruiting
        • Dokuz Eylul University Faculty of Medicine ( Site 0505)
        • Contact:
          • Study Coordinator
          • Phone Number: +902324122210
    • Izmir
      • Bornova, Izmir, Turkey, 35100
        • Recruiting
        • Ege Universitesi Hastanesi-Cardilogy Department ( Site 0504)
        • Contact:
          • Study Coordinator
          • Phone Number: +905324123489
  • United Kingdom
    • Glasgow City
      • Glasgow, Glasgow City, United Kingdom, G81 4DY
        • Recruiting
        • Golden Jubilee National Hospital ( Site 0556)
        • Contact:
          • Study Coordinator
          • Phone Number: +441419515497
    • London, City Of
      • London, London, City Of, United Kingdom, SW3 6NP
        • Recruiting
        • Royal Brompton and Harefield NHS Trust ( Site 0553)
        • Contact:
          • Study Coordinator
          • Phone Number: +4402073518362
      • London, London, City Of, United Kingdom, W12 0HS
        • Recruiting
        • Imperial College Healthcare NHS Trust - Hammersmith Hospital ( Site 0554)
        • Contact:
          • Study Coordinator
          • Phone Number: 07971655079
    • Newcastle Upon Tyne
      • Newcastle-upon-Tyne, Newcastle Upon Tyne, United Kingdom, NE7 7DN
        • Recruiting
        • The Freeman Hosp.Newcastle upon Tyne Hosp NHS Trust ( Site 0552)
        • Contact:
          • Study Coordinator
          • Phone Number: +441912231608
  • United States
    • California
      • La Jolla, California, United States, 92037-7381
        • Active, not recruiting
        • University of California San Diego Health-Pulmonary Critical Care ( Site 0061)
      • Sacramento, California, United States, 95817
        • Active, not recruiting
        • University of California Davis Health-Internal Medicine: Pulmonary, Critical Care and Sleep Medicine
      • San Francisco, California, United States, 94143
        • Completed
        • UCSF Helen Diller Medical Center at Parnassus Heights ( Site 0063)
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado - Denver ( Site 0003)
        • Contact:
          • Study Coordinator
          • Phone Number: 720-848-0000
      • Greeley, Colorado, United States, 80631
        • Completed
        • Cardiovascular Institute of North Colorado - Banner Health ( Site 0013)
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Completed
        • Georgetown University Hospital ( Site 0025)
    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami Hospital-Division of Pulmonary & Critical Care ( Site 0053)
        • Contact:
          • Study Coordinator
          • Phone Number: 305-243-2568
      • Orlando, Florida, United States, 32803
        • Recruiting
        • AdventHealth Orlando ( Site 0040)
        • Contact:
          • Study Coordinator
          • Phone Number: 407-303-7556
      • Tampa, Florida, United States, 33606
        • Recruiting
        • Tampa General Hospital ( Site 0058)
        • Contact:
          • Study Coordinator
          • Phone Number: 215-964-7399
    • Indiana
      • Indianapolis, Indiana, United States, 46202-1239
        • Recruiting
        • Indiana University Health Methodist Hospital ( Site 0045)
        • Contact:
          • Study Coordinator
          • Phone Number: 317-962-9700
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Completed
        • University of Iowa Hospital and Clinics ( Site 0009)
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • University of Kansas Medical Center ( Site 0038)
        • Contact:
          • Study Coordinator
          • Phone Number: 913-588-4022
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • University of Kentucky ( Site 0006)
        • Contact:
          • Study Coordinator
          • Phone Number: 859-323-0295
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • Norton Pulmonary Specialists ( Site 0048)
        • Contact:
          • Study Coordinator
          • Phone Number: 502-587-8000
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland ( Site 0032)
        • Contact:
          • Study Coordinator
          • Phone Number: 410-328-6885
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine ( Site 0066)
        • Contact:
          • Study Coordinator
          • Phone Number: 901-834-7034
    • Nebraska
      • Omaha, Nebraska, United States, 68198-7680
        • Recruiting
        • University of Nebraska Medical Center ( Site 0041)
        • Contact:
          • Study Coordinator
          • Phone Number: 402-559-7585
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • Active, not recruiting
        • University of New Mexico, Health Sciences Center ( Site 0028)
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • Active, not recruiting
        • Clinical Trials Unit at Eastowne Medical Office Building ( Site 0019)
    • South Carolina
      • Anderson, South Carolina, United States, 29621
        • Completed
        • AnMed Health ( Site 0033)
    • Tennessee
      • Knoxville, Tennessee, United States, 37934
        • Recruiting
        • Statcare Pulmonary Consultants ( Site 0067)
        • Contact:
          • Study Coordinator
          • Phone Number: 865-934-2672
    • Texas
      • Dallas, Texas, United States, 75390
        • Active, not recruiting
        • University of Texas Southwestern Medical Center at Dallas ( Site 0012)
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas Health Science Center at Houston ( Site 0054)
        • Contact:
          • Study Coordinator
          • Phone Number: 281-908-7912
      • Houston, Texas, United States, 77030
        • Completed
        • Houston Methodist Research Institute ( Site 0036)
    • Virginia
      • Norfolk, Virginia, United States, 23507
        • Completed
        • Sentara Norfolk General Hospital ( Site 0014)
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • Active, not recruiting
        • West Virginia University-WVU Heart and Vascular Institute ( Site 0051)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 2 Cohort MK-5475 380 µg
Participants receive MK-5475 380 µg via oral inhalation once daily for 12 week base period and for optional 24 month extension period.
Drug: MK-5475
MK-5475 (soluble guanylate cyclase stimulator) 380 µg, 100 µg or 32 µg administered as dry powder inhalation
Experimental: Phase 2 Cohort MK-5475 100 µg
Participants receive MK-5475 100 µg via oral inhalation once daily for 12 week base period and for optional 24 month extension period.
Drug: MK-5475
MK-5475 (soluble guanylate cyclase stimulator) 380 µg, 100 µg or 32 µg administered as dry powder inhalation
Experimental: Phase 2 Cohort MK-5475 32 µg
Participants receive MK-5475 32 µg via oral inhalation once daily for 12 week base period and for optional 24 month extension period.
Drug: MK-5475
MK-5475 (soluble guanylate cyclase stimulator) 380 µg, 100 µg or 32 µg administered as dry powder inhalation
Placebo Comparator: Phase 2 Cohort Placebo
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.
Drug: Placebo to MK-5475
Placebo administered as dry powder inhalation
Experimental: Phase 3 Cohort MK-5475
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
Drug: MK-5475
MK-5475 (soluble guanylate cyclase stimulator) 380 µg, 100 µg or 32 µg administered as dry powder inhalation
Placebo Comparator: Phase 3 Cohort Placebo
Participants receive placebo via oral inhalation once daily for 12 week base period and up to 60 months in the extension period.
Drug: Placebo to MK-5475
Placebo administered as dry powder inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 2 Cohort: Change from Baseline in Pulmonary Vascular Resistance (PVR) at 12 Weeks
Time Frame: At baseline and 12 weeks
PVR is assessed by right heart catheterization (RHC).
At baseline and 12 weeks
Phase 3 Cohort: Change from Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks
Time Frame: At baseline and 12 weeks
6MWD is assessed using the 6-minute walk test (6MWT).
At baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 2 Cohort: Change from Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks
Time Frame: At baseline and 12 weeks
6MWD is assessed using the 6-minute walk test (6MWT).
At baseline and 12 weeks
Phase 2 Cohort: Change from Baseline in Mean Right Arterial Pressure (mRAP) at 12 Weeks
Time Frame: At baseline and 12 weeks
mRAP is assessed by right heart catheterization (RHC).
At baseline and 12 weeks
Phase 2 Cohort: Change from Baseline in Cardiac Index (CI) at 12 weeks
Time Frame: At baseline and 12 weeks
Cardiac index is assessed by right heart catheterization (RHC).
At baseline and 12 weeks
Phase 2 Cohort: Change from Baseline in Stroke Volume Index (SVI) at 12 weeks
Time Frame: At baseline and 12 weeks
SVI is assessed by right heart catheterization (RHC).
At baseline and 12 weeks
Phase 3 Cohort: Change from Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks
Time Frame: At baseline and 24 weeks
6MWD is assessed using the 6-minute walk test (6MWT).
At baseline and 24 weeks
Phase 3 Cohort: Change from Baseline in World Health Organization Functional Class (WHO-FC) at 12 Weeks
Time Frame: At baseline and 12 weeks
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.
At baseline and 12 weeks
Phase 2 Cohort: Number of Participants Who Experience an Adverse Event
Time Frame: Up to approximately 2.25 years
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 approximately 2.25 years
Phase 2 Cohort: Number of Participants Who Discontinue Study Drug Due to an Adverse Event
Time Frame: Up to approximately 2.25 years
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 approximately 2.25 years
Phase 3 Cohort: Number of Participants who Experience an Adverse Event
Time Frame: Up to approximately 5.5 years
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 approximately 5.5 years
Phase 3 Cohort: Number of Participants who Discontinue Study Drug Due to an Adverse Event
Time Frame: Up to approximately 5.5 years
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 approximately 5.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 19, 2021

Primary Completion (Estimated)

February 9, 2026

Study Completion (Estimated)

January 19, 2028

Study Registration Dates

First Submitted

January 27, 2021

First Submitted That Met QC Criteria

January 27, 2021

First Posted (Actual)

February 1, 2021

Study Record Updates

Last Update Posted (Actual)

April 8, 2024

Last Update Submitted That Met QC Criteria

April 5, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5475-007
  • MK-5475-007 (Other Identifier: Merck)
  • 2020-001108-40 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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