Clinical Trial Finder

Inclusion Criteria:

• - Adult participants ≥ 18 years of age.

• - Symptomatic World Health Organization (WHO) Group 1 Pulmonary Hypertension (PH)(PAH) classified by one of the following subgroups: - Idiopathic pulmonary arterial hypertension (IPAH); - Heritable pulmonary arterial hypertension (HPAH); - Associated with drugs and toxins; - PAH associated with: - Connective tissue disease.

• - Congenital systemic-pulmonary intracardiac shunt.

• - Has the following hemodynamic parameters that are consistent with the diagnosis of PAH: - Mean pulmonary arterial pressure (mPAP) > 20 mmHg at rest, AND.

• - Pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg, AND.

• - PVR ≥ 5 Wood Units (400 dyn·sec·cm-5) - Has WHO/New York Heart Association (NYHA) Functional Class (FC) II or III symptoms as assessed by the Investigator.

• - Must be on a stable PAH background therapy with either an endothelin-receptor antagonist (ERA) and/or a phosphodiesterase-5 inhibitor (PDE5-I) or soluble guanylate cyclase (sGC) stimulator and/or prostacyclin analogue or receptor agonist (oral/inhaled/SC/intravenous) - 6MWD ≥ 150 and ≤ 500 meters at screening.

• - Provide written (signed and dated) informed consent form before the initiation of any Screening tests or procedures.

Exclusion Criteria:

• - Evidence or history of left ventricular dysfunction and/or clinically significant cardiac disease.

• - Has pulmonary function tests (PFTs) with evidence of significant obstructive or parenchymal lung disease.

• - Evidence of thromboembolic disease assessed by ventilation perfusion (V/Q) lung scan or other local standard of care diagnostic evaluation at the time of PAH diagnosis or after.

• - Has uncontrolled systemic hypertension.

• - Hemoglobin < 9 g/dL at Screening.

• - Prior heart or heart-lung transplants, active on the lung transplant list, or life expectancy of < 12 months per Investigator assessment.

• - Diagnosis of pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis.

• - Initiation or discontinuation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to Baseline or planned initiation during the study.

- Prior participation in a KER-012 study or prior treatment with a therapy targeting TGF-β superfamily (e.g. sotatercept) - Prior participation in another interventional clinical study with medicinal products within 30 days or 5 half-lives prior to Screening, whichever is longer

This is a randomized, phase 2, double-blind, placebo-controlled study of KER-012 in combination with background therapy in participants with PAH of World Health Organization (WHO) Group 1, functional class II-III. Participants will be randomly assigned in a 2:2:2:3 ratio to receive KER-012 (Dose A), KER-012 (Dose B), KER-012 (Dose C), or placebo by subcutaneous injection (SC) every 4 weeks for a period of 24 weeks in the placebo-controlled treatment period of the study while on background therapy. Evaluations will include changes in pulmonary vascular resistance (PVR), 6-minute walk distance (6MWD), and safety parameters. Participants who have not discontinued early from the placebo-controlled treatment period and have had their post-treatment period PVR assessment will be able to continue into the 72-week extension period in which KER-012 treated participants will continue to receive their same assigned dose level from the treatment period every 4 weeks and placebo treated participants will receive KER-012 (Dose B) every 4 weeks while on background therapy. For more information please check https://tropospahstudy.com/

Arms

Experimental: Arm 1 (N=20)

KER-012 (Dose A) subcutaneously (SC) (every 4 weeks [Q4W]) Treatment Period: Dose A for 24 weeks; Extension Period: Dose A for another 72 weeks

Experimental: Arm 2 (N=20)

KER-012 (Dose B) SC (Q4W) Treatment Period: Dose B for 24 weeks; Extension Period: Dose B for another 72 weeks

Experimental: Arm 3 (N=20)

KER-012 (Dose C) SC (Q4W) Treatment Period: Dose C for 24 weeks; Extension Period: Dose C for another 72 weeks

Placebo Comparator: Arm 4 (N=30)

Treatment Period: Placebo for 24 weeks; Extension Period: Dose B for another 72 weeks

Interventions

Biological: - Dose A KER-012

Dose A KER-012 (Q4W);

Biological: - Dose B KER-012

Dose B KER-012 (Q4W);

Biological: - Dose C KER-012

Dose C KER-012 (Q4W);

Biological: - Placebo for 24 Weeks followed by Dose B KER-012 for 72 weeks

Treatment Period (24 weeks): Placebo SC (Q4W) Extension Period (72 weeks after Placebo treatment): KER-012 (Dose B) SC (Q4W)