A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension

Overview

About this study

The purpose of this study is to evaluate the effect of sotatercept (ACE-011) in adults with Pulmonary Arterial Hypertension. Each eligible participant will receive standard of care (SOC) plus sotatercept (ACE-011) for a 24 week treatment period followed by a 16 week follow up period.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Age ≥ 18 years old.
  • Documented findings on RHC at any time prior to Screening consistent with a diagnosis of World Health Organization (WHO) pulmonary hypertension Group 1: PAH of any of the following subtypes:
    • Idiopathic PAH;
    • Heritable PAH;
    • Drug- or toxin-induced PAH;
    • PAH associated with connective tissue disease;
    • PAH associated with simple, congenital systemic-to-pulmonary shunts at least 1 year following shunt repair.
  • Symptomatic pulmonary hypertension classified as WHO functional class III.
  • Screening RHC documenting a minimum PVR of ≥ 4 Wood units.
  • Pulmonary function tests within 6 months prior to Screening as follows:
    • Total lung capacity > 70% predicted; or if between 60% to 70% predicted, or not possible to be determined, confirmatory high-resolution computed tomography (CT) indicating no more than mild interstitial lung disease per investigator interpretation; or
    •  Forced expiratory volume (first second) (FEV1)/forced vital capacity (FVC) > 70% predicted.
  • Ventilation-perfusion (VQ) scan (or, if unavailable, a negative CT pulmonary angiogram [CTPA] or pulmonary angiography result), any time prior to Screening or conducted during Screening Period with normal or low probability result.
  • 6MWD ≥ 100 and ≤ 550 meters repeated twice during Screening Period and both values within 15% of each other, calculated from the highest value 8.
  • Combination PAH therapy at stable (per investigator) dose levels for at least 90 days prior to Cycle 1 Day 1 (C1D1).

Exclusion Criteria:

Participants will be excluded from the study if they meet any of the following criteria:

  • Started or stopped receiving any general supportive therapy for pulmonary hypertension (e.g., diuretics, oxygen, anticoagulants, digoxin) within 60 days prior to C1D1 (Cycle 1 Day 1).
  • Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to C1D1.
  • History of atrial septostomy within 180 days prior to Screening.
  • History of more than mild obstructive sleep apnea that is untreated.
  • History of portal hypertension or chronic liver disease, defined as mild to severe hepatic impairment (Child-Pugh Classes A to C).
  • History of human immunodeficiency virus infection-associated PAH.
  • Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536).
  • Uncontrolled systemic hypertension as evidenced by sitting systolic BP > 160 mm Hg or sitting diastolic BP > 100 mm Hg during Screening after a period of rest.
  • Systolic BP < 90 mm Hg during Screening or at baseline.
  • History of known pericardial constriction.
  • History of personal or family history of long QTc syndrome or sudden cardiac death.
  • History of restrictive or constrictive cardiomyopathy.
  • Left ventricular ejection fraction < 45% on echocardiogram performed within 6 months of Screening OR PCWP > 15 mm Hg on RHC during baseline evaluation.
  • Any current symptomatic coronary disease (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain in the past 6 months prior to Screening).
  • Acutely decompensated heart failure within 30 days prior to C1D1, as per investigator assessment.
  • Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Robert Frantz, M.D.

Closed for enrollment

More information

Publications

Publications are currently not available
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