Details

IRB Study Number 22-659

Status Recruiting

Phase Phase 3

Location Cleveland Clinic Main Campus

Institute Respiratory Institute

Description

Description

The objective of this study is to evaluate the effects of sotatercept treatment (plus background PAH therapy) versus placebo (plus background PAH therapy) on time to clinical worsening (TTCW) in participants who are newly diagnosed with PAH and are at intermediate or high risk of disease progression.

Inclusion Criteria

Inclusion Criteria

Eligible participants must meet all of the following criteria to be enrolled in the study:

  1. Age ≥ 18 years
  2. Documented diagnostic right heart catheterization (RHC) within 6 months of screening documenting a minimum PVR of ≥ 4 Wood units and pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) of ≤ 15 mmHg, with the diagnosis of WHO PAH Group 1 in any of the following subtypes:

o Idiopathic PAH

o Heritable PAH

o Drug/toxin-induced PAH

o PAH associated with connective tissue disease

o PAH associated with simple, congenital systemic to pulmonary shunts at least 1 year following repair

  1. Symptomatic PAH classified as WHO FC II or III
  2. REVEAL Lite 2 Risk Score ≥ 6
  3. Diagnosis of PAH within 6 months of screening and on stable doses of a double combination of background PAH therapies for at least 90 days prior to screening. A triple combination of therapies, with stable doses for 90 days, may be allowed per local standard-of-care guidelines, but is restricted to 10% of the study population.
  4. Six-minute walk distance ≥ 150 m repeated twice at screening at least 4 hours apart, but no longer than 1 week apart, and both values are within 15% of each other (calculated from the highest value)
  5. Females of childbearing potential must meet the following criteria:

o Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting study drug administration; she must agree to ongoing urine or serum pregnancy testing during the course of the study and until 8 weeks after the last dose of the study drug

o If sexually active, have used, and agree to use, highly effective contraception without interruption, for at least 28 days prior to starting the investigational product, during the study (including dose interruptions), and for 16 weeks (112 days) after discontinuation of study treatment

o Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study treatment

  1. Male participants must meet the following criteria:

o Agree to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for at least 16 weeks (112 days) following investigational product discontinuation, even if he has undergone a successful vasectomy

o Refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study treatment

  1. Ability to adhere to study visit schedule and understand and comply with all protocol requirements
  2. Ability to understand and provide written informed consent

Exclusion Criteria

Exclusion Criteria

Participants will be excluded from the study if any of the following criteria are met:

  1. Diagnosis of PAH WHO Groups 2, 3, 4, or 5
  2. Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH and PAH associated with portal hypertension
  3. Hemoglobin at screening above gender-specific upper limit of normal (ULN), per local laboratory test
  4. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 160 mmHg or sitting diastolic BP > 100 mmHg during the Screening Visit after a period of rest
  5. Baseline systolic BP < 90 mmHg at screening
  6. Pregnant or breastfeeding women
  7. Any of the following clinical laboratory values at the Screening Visit:

o Estimated glomerular filtration rate < 30 mL/min/m2 (as defined by MDRD equation)

o Serum alanine aminotransferase or aspartate aminotransferase levels > 3 × ULN or total bilirubin > 1.5 × ULN

o Platelet count < 50,000/mm3 (< 50.0 × 109 /L)

  1. Currently enrolled in or have completed any other investigational product study within 30 days for small molecule drugs or within 5 half-lives for biologics prior to the date of signed informed consent
  2. Known allergic reaction to sotatercept (ACE-011)
  3. History of pneumonectomy
  4. Pulmonary function test values of forced vital capacity < 60% predicted within 1 year prior to the Screening Visit
  5. Stopped receiving any pulmonary hypertension chronic general supportive therapy (e.g., diuretics, oxygen, anticoagulants, and digoxin) within 60 days prior to the Screening Visit
  6. Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to the Screening Visit or planned initiation during the study (participants who are stable in the maintenance phase of a program and who will continue for the duration of the study are eligible)
  7. Untreated obstructive sleep apnea
  8. History of known pericardial constriction
  9. History of restrictive or congestive cardiomyopathy
  10. History of atrial septostomy within 180 days prior to the Screening Visit
    1. Electrocardiogram with Fridericia's corrected QT interval > 450 ms (or > 500 ms if right bundle branch abnormality is present) during the Screening Period
  12. Personal or family history of long QT syndrome or sudden cardiac death
  13. Left ventricular ejection fraction < 50% on historical echocardiogram within 1 year prior to the Screening Visit or pulmonary capillary wedge pressure > 15 mmHg as determined by historical RHC within 6 months prior to the Screening Visit
  14. Any current or prior history of symptomatic coronary disease (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) in the past 6 months prior to the Screening Visit
  15. Cerebrovascular accident within 3 months prior to the Screening Visit
  16. Acutely decompensated heart failure within 30 days prior to the Screening Visit, as per investigator assessment
  17. Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease

Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine