A Study to Investigate the Safety and Efficacy of KER-012 in Combination With Background Therapy in Adult Participants With Pulmonary Arterial Hypertension (PAH) (TROPOS Study).

Study KER-012-A201 is Phase 2, double-blind, randomized, placebo-controlled study to determine the efficacy and safety of KER-012 compared to Placebo in adults with PAH (WHO Group 1 PH) on stable background PAH therapy. The study is divided into the Screening Period, Treatment Period, Extension Period, and Follow-Up Period.

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.

Eligibility Criteria:
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