NCT04732221

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

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 168 (actual)
• Sponsor: Merck Sharp & Dohme LLC · Industry
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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 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.

Conditions

• Pulmonary Arterial Hypertension
• Hypertension, Pulmonary

Interventions

Type	Name	Description
DRUG	Frespaciguat	Frespaciguat (soluble guanylate cyclase stimulator) 380 µg, 100 µg or 32 µg administered as dry powder inhalation
DRUG	Placebo to Frespaciguat	Placebo administered as dry powder inhalation

Timeline

• Start date: 2021-05-19
• Primary completion: 2024-01-04
• Completion: 2024-07-02
• First posted: 2021-02-01
• Last updated: 2025-05-25
• Results posted: 2025-02-21

Locations

91 sites across 18 countries: United States, Argentina, Australia, Belgium, Canada, Colombia, France, Germany, Greece, Israel, Italy, Mexico, New Zealand, Poland, Russia, Sweden, Turkey (Türkiye), United Kingdom

Regulatory

• FDA-regulated drug study