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Pulmonary Arterial HypertensionPhase 2/3NCT04732221

A Study of the Efficacy and Safety of Frespaciguat (MK-5475) in Participants With Pulmonary Arterial Hypertension (INSIGNIA-PAH: Phase 2/3 Study of an Inhaled sGC Stimulator in PAH) (MK-5475-007)

A Phase 2/3 study testing Frespaciguat in people with Pulmonary Arterial Hypertension and Hypertension, Pulmonary, run by Merck Sharp & Dohme LLC at 91 sites in 18 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a two-part (Phase 2/Phase 3) study of frespaciguat, an inhaled soluble guanylate cyclase stimulator, in participants with pulmonary arterial hypertension (PAH). The first part (Phase 2) will assess three different doses of frespaciguat compared to placebo in a base period of 12 weeks, followed by comparison of… Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Frespaciguat
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
168 participants
Where
91 sitesin 18 countries
Study dates
19 May 2021to 2 Jul 2024
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
Show all 16Show fewer
  • 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.

Who cannot join

  • 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.
Show all 17Show fewer
  • 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.

Trial locations and contacts

91 sites in 18 countries.

91 sites in 18 countries

United States26 sites

  • University of New Mexico, Health Sciences Center ( Site 0028)

    Albuquerque, New Mexico, 87131

  • AnMed Health ( Site 0033)

    Anderson, South Carolina, 29621

  • University of Colorado - Denver ( Site 0003)

    Aurora, Colorado, 80045

  • University of Maryland ( Site 0032)

    Baltimore, Maryland, 21201

  • Clinical Trials Unit at Eastowne Medical Office Building ( Site 0019)

    Chapel Hill, North Carolina, 27514

  • University of Texas Southwestern Medical Center at Dallas ( Site 0012)

    Dallas, Texas, 75390

  • Cardiovascular Institute of North Colorado - Banner Health ( Site 0013)

    Greeley, Colorado, 80631

  • Houston Methodist Research Institute ( Site 0036)

    Houston, Texas, 77030

  • The University of Texas Health Science Center at Houston ( Site 0054)

    Houston, Texas, 77030

  • Indiana University Health Methodist Hospital ( Site 0045)

    Indianapolis, Indiana, 46202-1239

  • University of Iowa Hospital and Clinics ( Site 0009)

    Iowa City, Iowa, 52242

  • University of Kansas Medical Center ( Site 0038)

    Kansas City, Kansas, 66160

  • Statcare Pulmonary Consultants ( Site 0067)

    Knoxville, Tennessee, 37934

  • University of California San Diego Health-Pulmonary Critical Care ( Site 0061)

    La Jolla, California, 92037-7381

  • University of Kentucky ( Site 0006)

    Lexington, Kentucky, 40536

  • Norton Pulmonary Specialists ( Site 0048)

    Louisville, Kentucky, 40202

  • University of Miami Hospital-Division of Pulmonary & Critical Care ( Site 0053)

    Miami, Florida, 33136

  • West Virginia University-WVU Heart and Vascular Institute ( Site 0051)

    Morgantown, West Virginia, 26506

  • Sentara Norfolk General Hospital ( Site 0014)

    Norfolk, Virginia, 23507

  • University of Nebraska Medical Center ( Site 0041)

    Omaha, Nebraska, 68198

  • AdventHealth Orlando ( Site 0040)

    Orlando, Florida, 32803

  • University of California Davis Health-Internal Medicine: Pulmonary, Critical Care and Sleep Medicine

    Sacramento, California, 95817

  • UCSF Helen Diller Medical Center at Parnassus Heights ( Site 0063)

    San Francisco, California, 94143

  • Washington University School of Medicine ( Site 0066)

    St Louis, Missouri, 63110

  • Tampa General Hospital ( Site 0058)

    Tampa, Florida, 33606

  • Georgetown University Hospital ( Site 0025)

    Washington D.C., District of Columbia, 20007

Other trials in United States

Argentina8 sites

  • Sanatorio de la Trinidad Mitre ( Site 0130)

    Buenos Aires, Buenos Aires F.D., 1039

  • Cardiologia Palermo ( Site 0140)

    Ciudad Autonoma de Buenos Aires, Buenos Aires, C1425BNG

  • Hospital Privado Universitario de Córdoba ( Site 0137)

    Córdoba, X5016KEH

  • Centro Medico Capital ( Site 0131)

    La Plata, Buenos Aires, B1904AAW

  • Hospital Universitario Austral ( Site 0138)

    Pilar, Buenos Aires, B1629ODT

  • Instituto de Investigaciones Clinicas Quilmes ( Site 0141)

    Quilmes, Buenos Aires, B1878GEG

  • Instituto Cardiovascular de Rosario ( Site 0128)

    Rosario, Santa Fe Province, S2000DSR

  • Hospital El Cruce Nestor Carlos Kirchner ( Site 0132)

    San Juan Bautista, Buenos Aires, 1888

Other trials in Argentina

Turkey (Türkiye)8 sites

  • Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 0510)

    Ankara, 06100

  • Akdeniz Uni.Tip Fakultesi Saglik Uygulama ve Arastirma Merkezi ( Site 0508)

    Antalya, 07059

  • Ege Universitesi Hastanesi-Cardilogy Department ( Site 0504)

    Bornova, İzmir, 35100

  • Eskisehir Osmangazi Uni. Tip Fakultesi Hastanesi ( Site 0506)

    Eskişehir, 26040

  • Istanbul Uni. Kardiyoloji Enstitusu ( Site 0502)

    Istanbul, 34096

  • Istanbul Universitesi Istanbul Tip Fakultesi ( Site 0509)

    Istanbul, 34390

  • Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 0501)

    Istanbul, 34899

  • Dokuz Eylul University Faculty of Medicine ( Site 0505)

    Izmir, 35330

Other trials in Turkey (Türkiye)

Germany6 sites

  • Uniklinikum Dresden ( Site 0283)

    Dresden, Saxony, 01307

  • UKGM Gießen/Marburg ( Site 0279)

    Giessen, Hesse, 35392

  • Medizinische Hochschule Hannover ( Site 0284)

    Hanover, Lower Saxony, 30625

  • Thoraxklinik Heidelberg gGmbH am Universitaetsklinikum Heidelberg ( Site 0276)

    Heidelberg, Baden-Wurttemberg, 69126

  • Universitaetsklinikum Leipzig ( Site 0285)

    Leipzig, Saxony, 04103

  • Klinikum Würzburg Mitte-Medizinische Klinik - Schwerpunkt Pneumologie & Beatmungsmedizin ( Site 0280

    Würzburg, Bavaria, 97074

Other trials in Germany

France5 sites

  • CHRU Brest - Hopital Cavale Blanche ( Site 0254)

    Brest, Finistere, 29609

  • CHU - Hopital de Bicetre ( Site 0251)

    Le Kremlin-Bicêtre, Val-de-Marne, 94275

  • Institut Coeur Poumon - CHRU de Lille ( Site 0252)

    Lille, Hauts-de-France, 59037

  • Centre Hospitalier Universitaire de Rouen ( Site 0253)

    Rouen, Seine-Maritime, 76031

  • CHU de Toulouse - Hopital Larrey ( Site 0258)

    Toulouse, Haute-Garonne, 31059

Other trials in France

Israel5 sites

  • Soroka Medical Center ( Site 0330)

    Beersheba, 8410101

  • Rambam Medical Center ( Site 0335)

    Haifa, 3109601

  • Wolfson Medical Center [Holon, Israel] ( Site 0333)

    Holon, 5810000

  • Shaare Zedek Medical Center ( Site 0331)

    Jerusalem, 9103102

  • Rabin Medical Center ( Site 0327)

    Petah Tikva, 4941492

Other trials in Israel

Italy5 sites

  • Centro Cardiologico Monzino IRCCS ( Site 0306)

    Milan, 20138

  • Ospedale San Gerardo - ASST Monza ( Site 0304)

    Monza, Monza E Brianza, 20900

  • University of Naples Federico II ( Site 0308)

    Naples, Campania, 80100

  • Fondazione IRCCS Policlinico San Matteo ( Site 0302)

    Pavia, 27100

  • Azienda Ospedaliera Policlinico Umberto I ( Site 0301)

    Rome, Lazio, 00161

Other trials in Italy

United Kingdom4 sites

  • Golden Jubilee National Hospital ( Site 0556)

    Glasgow, Glasgow City, G81 4DY

  • Royal Brompton and Harefield NHS Trust ( Site 0553)

    London, London, City of, SW3 6NP

  • Imperial College Healthcare NHS Trust - Hammersmith Hospital ( Site 0554)

    London, London, City of, W12 0HS

  • The Freeman Hosp.Newcastle upon Tyne Hosp NHS Trust ( Site 0552)

    Newcastle upon Tyne, Newcastle Upon Tyne, NE7 7DN

Other trials in United Kingdom

Australia3 sites

  • Nepean Hospital ( Site 0184)

    Kingswood, New South Wales, 2747

  • Macquarie University ( Site 0180)

    Macquarie University, New South Wales, 2109

  • John Hunter Hospital ( Site 0185)

    Newcastle, New South Wales, 2305

Other trials in Australia

Canada3 sites

  • Peter Lougheed Centre ( Site 0107)

    Calgary, Alberta, T1Y 6J4

  • IUCPQ ( Site 0111)

    Québec, Quebec, G1V 4G5

  • University Health Network - Toronto General Hospital ( Site 0104)

    Toronto, Ontario, M5G 2N2

Other trials in Canada

Colombia3 sites

  • Hospital Universitario San Ignacio ( Site 0152)

    Bogotá, Bogota D.C., 110231

  • Centro Cardiovascular Colombiano Clínica Santa María ( Site 0154)

    Medellín, Antioquia, 050034

  • Fundacion Cardiovascular de Colombia ( Site 0155)

    Piedecuesta, Santander Department, 681017

Other trials in Colombia

Mexico3 sites

  • Operadora de Hospitales Angeles. S.A. de C.V. -Sucursal Lomas ( Site 0653)

    Huixquilucan, 52763

  • Instituto Nacional de Cardiología -Ignacio Chavez ( Site 0651)

    Mexico City, Mexico City, 14080

  • Consultorio 1020 Hospital Angeles Xalapa ( Site 0654)

    Xalapa, Veracruz, 91193

Other trials in Mexico

Poland3 sites

  • Krakowski Szpital Specjalistyczny im. Jana Pawa II-Oddzial Kliniczny Chorob Serca i Naczyn z Pododd

    Krakow, Lesser Poland Voivodeship, 31-202

  • Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie ( Site 0352)

    Lublin, Lublin Voivodeship, 20-954

  • Specjalistyczny Szpital im. Dr Alfreda Sokolowskiego w Walbrzychu ( Site 0351)

    Wałbrzych, Lower Silesian Voivodeship, 58-309

Other trials in Poland

Belgium2 sites

  • Université Libre de Bruxelles - Hôpital Erasme ( Site 0601)

    Brussels, Bruxelles-Capitale, Region de, 1070

  • UZ Leuven ( Site 0600)

    Leuven, Vlaams-Brabant, 3000

Other trials in Belgium

New Zealand2 sites

  • Greenlane Clinical Centre ( Site 0203)

    Auckland, 1051

  • Christchurch Hospital ( Site 0201)

    Christchurch, Canterbury, 8011

Other trials in New Zealand

Russia2 sites

  • Scientific Research Institute Complex Problems Cardiovascular Disease ( Site 0403)

    Kemerovo, Kemerovo Oblast, 650002

  • Almazov National Medical Research Centre of the Ministry of Health ( Site 0402)

    Saint Petersburg, Sankt-Peterburg, 197341

Other trials in Russia

Sweden2 sites

  • Sahlgrenska Universitetssjukhuset-Cardiology Research Unit ( Site 0452)

    Gothenburg, Västra Götaland County, 413 45

  • Akademiska sjukhuset ( Site 0453)

    Uppsala, Uppsala County, 751 85

Other trials in Sweden

Greece1 site

  • AHEPA University General Hospital of Thessaloniki ( Site 0577)

    Thessaloniki, 54636

Other trials in Greece

About this study

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

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

The first part (Phase 2) will assess three different doses of frespaciguat compared to placebo in a base period of 12 weeks, followed by comparison of three different doses of frespaciguat during an optional 40 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 frespaciguat 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 frespaciguat 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 frespaciguat is superior to placebo in increasing 6-minute walk distance (6MWD) from baseline at week 12. Due to sponsor's decision this phase/part was not conducted.

Being tested
Frespaciguat, Placebo to Frespaciguat
Medical subject headings
Pulmonary Arterial Hypertension, Hypertension, Pulmonary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FrespaciguatDrug

    Frespaciguat (soluble guanylate cyclase stimulator) 380 µg, 100 µg or 32 µg administered as dry powder inhalation

  • Placebo to FrespaciguatDrug

    Placebo administered as dry powder inhalation

Study groups in NCT04732221
Study groupRoleWhat they receive
Phase 2 Cohort Frespaciguat 380 µgExperimentalParticipants receive frespaciguat 380 µg via oral inhalation once daily for 12 week base period and for optional 40 month extension period.
Receives: Drug: Frespaciguat
Phase 2 Cohort Frespaciguat 100 µgExperimentalParticipants receive frespaciguat 100 µg via oral inhalation once daily for 12 week base period and for optional 40 month extension period.
Receives: Drug: Frespaciguat
Phase 2 Cohort Frespaciguat 32 µgExperimentalParticipants receive frespaciguat 32 µg via oral inhalation once daily for 12 week base period and for optional 40 month extension period.
Receives: Drug: Frespaciguat
Phase 2 Cohort PlaceboPlacebo comparatorParticipants 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 40 month extension period.
Receives: Drug: Placebo to Frespaciguat
Phase 3 Cohort FrespaciguatExperimentalParticipants receive one of 3 frespaciguat 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 40 months in the extension period
Receives: Drug: Frespaciguat
Phase 3 Cohort PlaceboPlacebo comparatorParticipants receive placebo via oral inhalation once daily for 12 week base period and up to 40 months in the extension period.
Receives: Drug: Placebo to Frespaciguat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 2 Cohort: Mean Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at 12 Weeks

    PVR was calculated in participants after MK-5475 dosing at baseline and Week 12. PVR is assessed by right heart catheterization (RHC). Based on the variables obtained by right heart catheterization (RHC), the percentage change from baseline PVR was calculated. Per protocol, this outcome measure was assessed only for base period and was not assessed during extension period.

    Measured: At baseline and 12 weeks

  2. Phase 3 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks

    6MWD is measured by an exercise test known as 6-Minute Walk Test (6MWT) that assesses functional capacity. It measures the distance covered over a time of 6 minutes and is intended to be used as an outcome measure by which to compare changes in excercise capacity. Each participant's 6MWD is to be measured at baseline and at 12 weeks. An increase in the distance walked during the 6MWT indicates improvement in functional exercise capacity.

    Measured: At baseline and 12 weeks

Secondary outcomes (10)

  1. Phase 2 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 12 Weeks

    6MWD is measured by an exercise test known as 6-Minute Walk Test (6MWT) that assesses functional capacity. It measures the distance covered over a time of 6 minutes and is used as an outcome measure by which to compare changes in exercise capacity. Each participant's 6MWD was measured at baseline and at 12 weeks. An increase in the distance walked during the 6MWT indicates improvement in functional exercise capacity.

    Measured: At baseline and 12 weeks

  2. Phase 2 Cohort: Mean Change From Baseline in Mean Right Atrial Pressure (mRAP) at 12 Weeks

    mRAP is the blood pressure in the right atrium of the heart. mRAP was assessed by right heart catheterization (RHC).A decrease in mRAP indicates improvement in right ventricular function, reduction of PAH related morbidity.

    Measured: At baseline and 12 weeks

  3. Phase 2 Cohort: Mean Change From Baseline in Cardiac Index (CI) at 12 Weeks

    The cardiac index (CI) is a hemodynamic measure that represents the cardiac output (CO) of an individual divided by their body surface area (BSA). Cardiac index is assessed by right heart catheterization (RHC). An increase in CI is indicates better right ventricular function and is associated with a reduction of PAH related morbidity and mortality.

    Measured: At baseline and 12 weeks

  4. Phase 2 Cohort: Mean Change From Baseline in Stroke Volume Index (SVI) at 12 Weeks

    The stroke volume index represents the amount of blood in mL, per square meter of body surface area, that is mobilized with each heart beat. SVI is assessed by RHC. An increase in SVI indicates better right ventricular function and is associated with a reduction of PAH related morbidity and mortality.

    Measured: At baseline and 12 weeks

  5. Phase 3 Cohort: Mean Change From Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks

    6MWD is measured by an exercise test known as 6-Minute Walk Test (6MWT) that assesses functional capacity. It measures the distance covered over a time of 6 minutes and is intended to be used as an outcome measure by which to compare changes in exercise capacity. Each participant's 6MWD is to be measured at baseline and at 24 weeks. An increase in the distance walked during the 6MWT indicates improvement in functional exercise capacity.

    Measured: At baseline and 24 weeks

  6. Phase 3 Cohort: Proportion of Participants Whose World Health Organization Functional Class (WHO-FC) is Not Worse at 12 Week Relative to Baseline

    The World Health Organization (WHO) classification of functional status is a measure of disease severity, based on a patient's description of their level of functioning and symptoms of disease in relation to their everyday activity. Patients were to be assigned 1 of 4 WHO-FC, dependent on limits of physical activity. As WHO-FC increases from I to IV, limits of physical activity were to increase.

    Measured: At baseline and 12 weeks

  7. Phase 2 Cohort: Number of Participants Who Experienced 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.

    Measured: Up to approximately 2.25 years

  8. Phase 2 Cohort: Number of Participants Who Discontinued 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. The number of participants who discontinued treatment due to an AE was assessed.

    Measured: Up to approximately 2.25 years

  9. Phase 3 Cohort: Number of Participants Who Experienced 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.

    Measured: Up to approximately 2.25 years

  10. Phase 3 Cohort: Number of Participants Who Discontinued Study Drug 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 number of participants who discontinued treatment due to an AE was assessed.

    Measured: Up to approximately 2.25 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Feb 2021
  2. Study start19 May 2021
  3. Primary completion4 Jan 2024
  4. Study completion2 Jul 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
A total of approximately 450 participants will be randomized in this operationally seamless adaptive Phase 2/3 study. Phase 2 of the study will randomize approximately 164 participants into 4 arms, and Phase 3 of the study will randomize approximately 286 participants into 2 arms.
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
168 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04732221
Sponsor's protocol ID
5475-007
Other IDs
MK-5475-007, 2022-500877-15-00, U1111-1278-4977, 2020-001108-40
Status last verified
May 2025
First submitted
27 Jan 2021
Last updated
25 May 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • Humbert M, Hassoun PM, Chin KM, Bortman G, Patel MJ, La Rosa C, Fu W, Loureiro MJ, Hoeper MM. MK-5475, an inhaled soluble guanylate cyclase stimulator, for treatment of pulmonary arterial hypertension: the INSIGNIA-PAH study. Eur Respir J. 2024 Nov 14;64(5):2401110. doi: 10.1183/13993003.01110-2024. Print 2024 Nov.

    PubMed 39255991

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Frespaciguat in people with Pulmonary Arterial Hypertension and Hypertension, Pulmonary, run by Merck Sharp & Dohme LLC at 91 sites in 18 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 91 sites in United States, Argentina, Turkey (Türkiye), Germany, France and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 2 Cohort: Mean Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at 12 Weeks (time frame: At baseline and 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04732221, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2025.

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