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

  • STATUS
    Recruiting
  • End date
    Oct 29, 2026
  • participants needed
    450
  • sponsor
    Merck Sharp & Dohme Corp.
Updated on 12 September 2021
body mass index
heart disease
pulmonary arterial hypertension
right heart catheterization
left ventricular end-diastolic pressure

Summary

This is a two-part (Phase 2/Phase 3) study of MK-5475, an inhaled soluble guanylate cyclase stimulator, in participants with pulmonary arterial hypertension (PAH).

The first part (Phase 2) will assess three different doses of MK-5475 compared to placebo; the treatment dose with the best efficacy and safety profile 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 MK-5475 dose group 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 MK-5475 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 MK-5475 is superior to placebo in increasing 6-minute walk distance (6MWD) from baseline at week 12.

Details
Condition Pulmonary Hypertension, Cancer Prevention, Surviving Abuse, Joint Injuries, Abdominal Surgery, Mental Disability, Pelvic Adhesions, Low Testosterone, Dental Filling, Habit Reversal, Complicated Grief, Chronic Pelvic Pain, Gambling Problems, Myopic Macular Degeneration, Nerve Injury, Severe Premenstrual Symptom, Stasis Dermatitis, Pulmonary Arterial Hypertension, Open Heart Surgery, Recurrent Pregnancy Loss, Effects of Chemotherapy, Renal Anemia, Functional Dyspepsia, Catheter Complications, Serial Evaluation of Ductal Epithelium, Chronic Renal Anemia, Cancer Treatment, Anemic Cancer, Spinocerebellar Disorders, Pseudobulbar Affect, Spine Athroplasty, Indikation: Diabetes - Typ II, Partial Medial Meniscectomy, Primary Insulin Hypersecretion, Testotoxikose, Infantile Fibrosarcoma, Late Infantile Neuronal Ceroid Lipfuscinsosis, Memory Problems
Treatment MK-5475, Placebo to MK-5475
Clinical Study IdentifierNCT04732221
SponsorMerck Sharp & Dohme Corp.
Last Modified on12 September 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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 450 meters, one at screening and one at randomization
Stable concomitant background PAH-specific therapy
Body Mass Index (BMI) between 18.5 kg/m and 40 kg/m
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

Exclusion Criteria

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 untreated obstructive sleep apnea (OSA)
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/m, essential systemic hypertension, diabetes mellitus of any type, or coronary artery disease
Oxygen saturation measured by pulse oximetry (SpO) <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
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