Frespaciguat (MK-5475) INSIGNIA-PH-COPD: A Study of the Efficacy and Safety of Frespaciguat (an Inhaled sGC Stimulator) in Adults With PH-COPD

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 2

Conditions: Chronic Obstructive Pulmonary Disease; Pulmonary Hypertension

Treatments: Drug: Placebo; Drug: Frespaciguat

Study type: Interventional

Funder types: Industry

Identifiers

NCT05612035

U1111-1279-8512 (Registry Identifier)

5475-013

2022-501201-13-00 (Registry Identifier)

MK-5475-013 (Other Identifier)

Details and patient eligibility

About

Researchers are looking for ways to treat pulmonary hypertension (PH) caused by chronic obstructive pulmonary disease (COPD). The goal of the study is to learn if people who take frespaciguat can walk farther in 6 minutes at Week 24 compared to people who take placebo.

Enrollment: 120 estimated patients

Sex: All

Ages: 40 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

The key inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• Has Group 3.1 pulmonary hypertension chronic obstructive pulmonary disease (PH-COPD) as defined by the Clinical Classification of Pulmonary Hypertension.
• Has a right heart catheterization (RHC) at screening or historical RHC within 12 months before screening that meets hemodynamic criteria.
• Has a physician diagnosis of obstructive lung disease on pulmonary function testing (PFT) performed at screening.
• Has a WHO Functional Class assessment of Class II to IV.
• If on supplemental oxygen, the regimen must be stable.
• Has stable and optimized chronic, baseline COPD-specific therapy.
• If on PDE5 inhibitor, has stable concomitant use (initiated at least 3 months prior to randomization and no change in drug or dosage for at least 3 months prior to randomization) and changes to PDE5 inhibitor dosing is not anticipated during the 24 week Base Period.
• If on antihypertensives and/or a diuretic regimen has stable concomitant use.
• If on anticoagulants has stable concomitant use.
• Is of any sex/gender from 40 to 85 years of age inclusive.
• Female is not pregnant or breastfeeding, and is not of childbearing potential or uses acceptable contraceptive method or abstains from sexual intercourse, or has a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention, or whose history and sexual activity has been reviewed by the investigator.

Exclusion criteria:

• Has Group 1 pulmonary arterial hypertension (PAH), Groups 2, 4 or 5 pulmonary hypertension (PH).
• Has non-COPD related Group 3 PH.
• Has evidence of untreated more than mild obstructive sleep apnea.
• Has significant left heart disease.
• Expects to receive a lung and/or heart transplant from screening through the end of the 24 week Base Period.
• Has evidence of a resting oxygen saturation (SpO2) < 88%.
• Has experienced a moderate or severe COPD exacerbation within 2 months before randomization.
• Has experienced right heart failure within 2 months before randomization.
• Has uncontrolled tachyarrhythmia.
• Has acute coronary syndrome, undergone coronary artery bypass graft, or percutaneous coronary intervention within 2 months before randomization.
• Has evidence of significant chronic renal insufficiency.
• Has evidence of chronic liver disease, portal hypertension, cirrhosis, or hepatic abnormalities.
• Initiated a pulmonary rehabilitation program within 2 months before randomization.
• Has impairments that limit the ability to perform 6MWT.
• Has history of cancer.
• Is a user of illicit drugs or has a recent history of drug/alcohol abuse or dependence.
• Has used PAH-specific therapies within 2 months of randomization.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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120 participants in 2 patient groups, including a placebo group

Frespaciguat

Experimental group

Description:

Participants with PH-COPD will receive 380 µg of frespaciguat as an oral inhalation once daily for 24 weeks (base period) and thereafter for up to 42 months (optional extension period).

Treatment:

Drug: Frespaciguat

Placebo

Placebo Comparator group

Description:

Participants with PH-COPD will receive matching placebo as an oral inhalation once daily for 24 weeks (base period) and then 380 µg of frespaciguat as an oral inhalation once daily for up to 42 months (optional extension period).

Treatment:

Drug: Frespaciguat

Drug: Placebo