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)

Completed · Phase 2/Phase 3 · Has a placebo group

Conditions studied: Pulmonary Arterial Hypertension, Hypertension, Pulmonary

In brief

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.

Key facts

Study ID: NCT04732221
Run by: Merck Sharp & Dohme LLC
People needed: 168
Starts: 2021-05-19
Expected to finish: 2024-07-02
Last updated by the study team: 2025-05-25

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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.

You may not qualify if…

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.

Where it is running

University of California Davis Health-Internal Medicine: Pulmonary, Critical Care and Sleep Medicine — Sacramento, California, United States
UCSF Helen Diller Medical Center at Parnassus Heights ( Site 0063) — San Francisco, California, United States
University of Colorado - Denver ( Site 0003) — Aurora, Colorado, United States
Cardiovascular Institute of North Colorado - Banner Health ( Site 0013) — Greeley, Colorado, United States
Georgetown University Hospital ( Site 0025) — Washington D.C., District of Columbia, United States
University of Miami Hospital-Division of Pulmonary & Critical Care ( Site 0053) — Miami, Florida, United States
AdventHealth Orlando ( Site 0040) — Orlando, Florida, United States
Tampa General Hospital ( Site 0058) — Tampa, Florida, 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
University of Kentucky ( Site 0006) — Lexington, Kentucky, United States
Norton Pulmonary Specialists ( Site 0048) — Louisville, Kentucky, United States
University of Maryland ( Site 0032) — Baltimore, Maryland, United States
Washington University School of Medicine ( Site 0066) — St Louis, Missouri, United States
University of Nebraska Medical Center ( Site 0041) — Omaha, Nebraska, United States
University of New Mexico, Health Sciences Center ( Site 0028) — Albuquerque, New Mexico, United States
Clinical Trials Unit at Eastowne Medical Office Building ( Site 0019) — Chapel Hill, North Carolina, United States
AnMed Health ( Site 0033) — Anderson, South Carolina, United States
Statcare Pulmonary Consultants ( Site 0067) — Knoxville, Tennessee, United States
University of Texas Southwestern Medical Center at Dallas ( Site 0012) — Dallas, Texas, 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
Sentara Norfolk General Hospital ( Site 0014) — Norfolk, Virginia, United States
University of California San Diego Health-Pulmonary Critical Care ( Site 0061) — La Jolla, California, United States

Full record on ClinicalTrials.gov

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