Pulmonary Arterial Hypertension Clinical Trial
Official title:
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
| Verified date | May 2024 |
| Source | Merck Sharp & Dohme LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 168 |
| Est. completion date | July 15, 2024 |
| Est. primary completion date | January 4, 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 75 Years |
| Eligibility | 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. |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Sanatorio de la Trinidad Mitre ( Site 0130) | Buenos Aires | Caba |
| Argentina | Cardiologia Palermo ( Site 0140) | Ciudad Autonoma de Buenos Aires | Buenos Aires |
| Argentina | Hospital Privado Universitario de Córdoba ( Site 0137) | Cordoba | |
| Argentina | Hospital El Cruce Nestor Carlos Kirchner ( Site 0132) | Florencio Varela | Buenos Aires |
| Argentina | Centro Medico Capital ( Site 0131) | La Plata | Buenos Aires |
| Argentina | Hospital Universitario Austral ( Site 0138) | Pilar | Buenos Aires |
| Argentina | Instituto de Investigaciones Clinicas Quilmes ( Site 0141) | Quilmes | Buenos Aires |
| Argentina | Instituto Cardiovascular de Rosario ( Site 0128) | Rosario | Santa Fe |
| Australia | Nepean Hospital ( Site 0184) | Kingswood | New South Wales |
| Australia | Macquarie University ( Site 0180) | Macquarie University | New South Wales |
| Australia | John Hunter Hospital ( Site 0185) | Newcastle | New South Wales |
| Belgium | Université Libre de Bruxelles - Hôpital Erasme ( Site 0601) | Brussels | Bruxelles-Capitale, Region De |
| Belgium | UZ Leuven ( Site 0600) | Leuven | Vlaams-Brabant |
| Canada | Peter Lougheed Centre ( Site 0107) | Calgary | Alberta |
| Canada | IUCPQ ( Site 0111) | Quebec | |
| Canada | University Health Network - Toronto General Hospital ( Site 0104) | Toronto | Ontario |
| Colombia | Hospital Universitario San Ignacio ( Site 0152) | Bogota | Distrito Capital De Bogota |
| Colombia | Centro Cardiovascular Colombiano Clínica Santa María ( Site 0154) | Medellín | Antioquia |
| Colombia | Fundacion Cardiovascular de Colombia ( Site 0155) | Piedecuesta | Santander |
| France | CHRU Brest - Hopital Cavale Blanche ( Site 0254) | Brest | Finistere |
| France | CHU - Hopital de Bicetre ( Site 0251) | Le Kremlin-Bicetre | Val-de-Marne |
| France | Institut Coeur Poumon - CHRU de Lille ( Site 0252) | Lille Cedex | Nord-Pas-de-Calais |
| France | Centre Hospitalier Universitaire de Rouen ( Site 0253) | Rouen | Seine-Maritime |
| France | CHU de Toulouse - Hopital Larrey ( Site 0258) | Toulouse | Haute-Garonne |
| Germany | Uniklinikum Dresden ( Site 0283) | Dresden | Sachsen |
| Germany | UKGM Gießen/Marburg ( Site 0279) | Gießen | Hessen |
| Germany | Medizinische Hochschule Hannover ( Site 0284) | Hannover | Niedersachsen |
| Germany | Thoraxklinik Heidelberg gGmbH am Universitaetsklinikum Heidelberg ( Site 0276) | Heidelberg | Baden-Wurttemberg |
| Germany | Universitaetsklinikum Leipzig ( Site 0285) | Leipzig | Sachsen |
| Germany | Klinikum Würzburg Mitte-Medizinische Klinik - Schwerpunkt Pneumologie & Beatmungsmedizin ( Site 0280 | Wuerzburg | Bayern |
| Greece | AHEPA University General Hospital of Thessaloniki ( Site 0577) | Thessaloniki | |
| Israel | Soroka Medical Center ( Site 0330) | Beer Sheva | |
| Israel | Rambam Medical Center ( Site 0335) | Haifa | |
| Israel | Wolfson Medical Center [Holon, Israel] ( Site 0333) | Holon | |
| Israel | Shaare Zedek Medical Center ( Site 0331) | Jerusalem | |
| Israel | Rabin Medical Center ( Site 0327) | Petah Tikva | |
| Italy | Centro Cardiologico Monzino IRCCS ( Site 0306) | Milano | |
| Italy | Ospedale San Gerardo - ASST Monza ( Site 0304) | Monza | Monza E Brianza |
| Italy | University of Naples Federico II ( Site 0308) | Naples | Campania |
| Italy | Fondazione IRCCS Policlinico San Matteo ( Site 0302) | Pavia | |
| Italy | Azienda Ospedaliera Policlinico Umberto I ( Site 0301) | Roma | Lazio |
| Mexico | Operadora de Hospitales Angeles. S.A. de C.V. -Sucursal Lomas ( Site 0653) | Huixquilucan | |
| Mexico | Instituto Nacional de Cardiología -Ignacio Chavez ( Site 0651) | Mexico D.F | |
| Mexico | Consultorio 1020 Hospital Angeles Xalapa ( Site 0654) | Xalapa | Veracruz |
| New Zealand | Greenlane Clinical Centre ( Site 0203) | Auckland | |
| New Zealand | Christchurch Hospital ( Site 0201) | Christchurch | Canterbury |
| Poland | Krakowski Szpital Specjalistyczny im. Jana Pawa II-Oddzial Kliniczny Chorob Serca i Naczyn z Pododd | Krakow | Malopolskie |
| Poland | Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie ( Site 0352) | Lublin | Lubelskie |
| Poland | Specjalistyczny Szpital im. Dr Alfreda Sokolowskiego w Walbrzychu ( Site 0351) | Walbrzych | Dolnoslaskie |
| Russian Federation | Scientific Research Institute Complex Problems Cardiovascular Disease ( Site 0403) | Kemerovo | Kemerovskaya Oblast |
| Russian Federation | Almazov National Medical Research Centre of the Ministry of Health ( Site 0402) | Saint Petersburg | Sankt-Peterburg |
| Sweden | Sahlgrenska Universitetssjukhuset-Cardiology Research Unit ( Site 0452) | Gothenburg | Vastra Gotalands Lan |
| Sweden | Akademiska sjukhuset ( Site 0453) | Uppsala | Uppsala Lan |
| Turkey | Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 0510) | Ankara | |
| Turkey | Akdeniz Uni.Tip Fakultesi Saglik Uygulama ve Arastirma Merkezi ( Site 0508) | Antalya | |
| Turkey | Ege Universitesi Hastanesi-Cardilogy Department ( Site 0504) | Bornova | Izmir |
| Turkey | Eskisehir Osmangazi Uni. Tip Fakultesi Hastanesi ( Site 0506) | Eskisehir | |
| Turkey | Istanbul Uni. Kardiyoloji Enstitusu ( Site 0502) | Istanbul | |
| Turkey | Istanbul Universitesi Istanbul Tip Fakultesi ( Site 0509) | Istanbul | |
| Turkey | Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 0501) | Istanbul | |
| Turkey | Dokuz Eylul University Faculty of Medicine ( Site 0505) | Izmir | |
| United Kingdom | Golden Jubilee National Hospital ( Site 0556) | Glasgow | Glasgow City |
| United Kingdom | Imperial College Healthcare NHS Trust - Hammersmith Hospital ( Site 0554) | London | London, City Of |
| United Kingdom | Royal Brompton and Harefield NHS Trust ( Site 0553) | London | London, City Of |
| United Kingdom | The Freeman Hosp.Newcastle upon Tyne Hosp NHS Trust ( Site 0552) | Newcastle-upon-Tyne | Newcastle Upon Tyne |
| United States | University of New Mexico, Health Sciences Center ( Site 0028) | Albuquerque | New Mexico |
| United States | AnMed Health ( Site 0033) | Anderson | South Carolina |
| United States | University of Colorado - Denver ( Site 0003) | Aurora | Colorado |
| United States | University of Maryland ( Site 0032) | Baltimore | Maryland |
| United States | Clinical Trials Unit at Eastowne Medical Office Building ( Site 0019) | Chapel Hill | North Carolina |
| United States | University of Texas Southwestern Medical Center at Dallas ( Site 0012) | Dallas | Texas |
| United States | Cardiovascular Institute of North Colorado - Banner Health ( Site 0013) | Greeley | Colorado |
| United States | Houston Methodist Research Institute ( Site 0036) | Houston | Texas |
| United States | The University of Texas Health Science Center at Houston ( Site 0054) | Houston | Texas |
| United States | Indiana University Health Methodist Hospital ( Site 0045) | Indianapolis | Indiana |
| United States | University of Iowa Hospital and Clinics ( Site 0009) | Iowa City | Iowa |
| United States | University of Kansas Medical Center ( Site 0038) | Kansas City | Kansas |
| United States | Statcare Pulmonary Consultants ( Site 0067) | Knoxville | Tennessee |
| United States | University of California San Diego Health-Pulmonary Critical Care ( Site 0061) | La Jolla | California |
| United States | University of Kentucky ( Site 0006) | Lexington | Kentucky |
| United States | Norton Pulmonary Specialists ( Site 0048) | Louisville | Kentucky |
| United States | University of Miami Hospital-Division of Pulmonary & Critical Care ( Site 0053) | Miami | Florida |
| United States | West Virginia University-WVU Heart and Vascular Institute ( Site 0051) | Morgantown | West Virginia |
| United States | Sentara Norfolk General Hospital ( Site 0014) | Norfolk | Virginia |
| United States | University of Nebraska Medical Center ( Site 0041) | Omaha | Nebraska |
| United States | AdventHealth Orlando ( Site 0040) | Orlando | Florida |
| United States | University of California Davis Health-Internal Medicine: Pulmonary, Critical Care and Sleep Medicine | Sacramento | California |
| United States | Washington University School of Medicine ( Site 0066) | Saint Louis | Missouri |
| United States | UCSF Helen Diller Medical Center at Parnassus Heights ( Site 0063) | San Francisco | California |
| United States | Tampa General Hospital ( Site 0058) | Tampa | Florida |
| United States | Georgetown University Hospital ( Site 0025) | Washington | District of Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC |
United States, Argentina, Australia, Belgium, Canada, Colombia, France, Germany, Greece, Israel, Italy, Mexico, New Zealand, Poland, Russian Federation, Sweden, Turkey, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Phase 2 Cohort: Change from Baseline in Pulmonary Vascular Resistance (PVR) at 12 Weeks | PVR is assessed by right heart catheterization (RHC). | At baseline and 12 weeks | |
| Primary | Phase 3 Cohort: Change from Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks | 6MWD is assessed using the 6-minute walk test (6MWT). | At baseline and 12 weeks | |
| Secondary | Phase 2 Cohort: Change from Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks | 6MWD is assessed using the 6-minute walk test (6MWT). | At baseline and 12 weeks | |
| Secondary | Phase 2 Cohort: Change from Baseline in Mean Right Arterial Pressure (mRAP) at 12 Weeks | mRAP is assessed by right heart catheterization (RHC). | At baseline and 12 weeks | |
| Secondary | Phase 2 Cohort: Change from Baseline in Cardiac Index (CI) at 12 weeks | Cardiac index is assessed by right heart catheterization (RHC). | At baseline and 12 weeks | |
| Secondary | Phase 2 Cohort: Change from Baseline in Stroke Volume Index (SVI) at 12 weeks | SVI is assessed by right heart catheterization (RHC). | At baseline and 12 weeks | |
| Secondary | Phase 3 Cohort: Change from Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks | 6MWD is assessed using the 6-minute walk test (6MWT). | At baseline and 24 weeks | |
| Secondary | Phase 3 Cohort: Change from Baseline in World Health Organization Functional Class (WHO-FC) at 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 | |
| Secondary | Phase 2 Cohort: Number of Participants Who Experience an Adverse Event | 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 | |
| Secondary | Phase 2 Cohort: Number of Participants Who Discontinue Study Drug Due to an Adverse Event | 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 | |
| Secondary | Phase 3 Cohort: Number of Participants who Experience an Adverse Event | 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 | |
| Secondary | Phase 3 Cohort: Number of Participants who Discontinue Study Drug Due to an Adverse Event | 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 |
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