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).

Conditions: Pulmonary Arterial Hypertension

Summary: 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

Keywords: pulmonary arterial hypertension [pah]