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)
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.
Timeline
- Start
- 2021-05-19
- Primary completion
- 2024-01-04
- Completion
- 2024-07-02
Outcome
Met primary endpoint
registry analysis (superiority test); Base Period: Placebo vs Base Period: MK-5475 100 µg; p <0.001; Treatment difference -22.0 (95% CI -33.7 to -10.3) NCT04732221 ↗
registry analysis (superiority test); Base Period: Placebo vs Base Period: MK-5475 380 µg; p = 0.002; Treatment difference -19.9 (95% CI -33.4 to -6.4) NCT04732221 ↗
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Frespaciguat | Small molecule | 32 ug | Inhaled |
| Subject | Frespaciguat | Small molecule | 100 ug | Inhaled |
| Subject | Frespaciguat | Small molecule | 380 ug | Inhaled |