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).

Keros Therapeutics

Status and phase: Enrolling; Phase 2

Conditions: Pulmonary Arterial Hypertension

Treatments: Biological: Dose B KER-012; Biological: Placebo for 24 Weeks followed by Dose B KER-012 for 72 weeks; Biological: Dose C KER-012; Biological: Dose A KER-012

Study type: Interventional

Funder types: Industry

Identifiers

NCT05975905

KER-012-A201

Details and patient eligibility

About

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.

Full description

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/

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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90 participants in 4 patient groups, including a placebo group

Arm 1 (N=20)

Experimental group

Description:

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

Treatment:

Biological: Dose A KER-012

Arm 2 (N=20)

Experimental group

Description:

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

Treatment:

Biological: Dose B KER-012

Arm 3 (N=20)

Experimental group

Description:

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

Treatment:

Biological: Dose C KER-012

Arm 4 (N=30)

Placebo Comparator group

Description:

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

Treatment:

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

Biological: Dose B KER-012