A Study of Sotatercept in Participants With PAH WHO FC III or FC IV at High Risk of Mortality

• Status: Recruiting
• Trial end date: 2026-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The objective of this study is to evaluate the effects of sotatercept treatment (plus maximum tolerated background PAH therapy) versus placebo (plus maximum tolerated background PAH therapy) on time to first event of all cause death, lung transplantation, or PAH worsening-related hospitalization of ≥ 24 hours, in participants with WHO FC III or FC IV PAH at high risk of mortality.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Acceleron Pharma Inc.

Criteria

Inclusion Criteria:

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

1. Age 18 to 75 years, inclusive

2. Documented diagnostic right heart catheterization prior to screening confirming the diagnosis of WHO PAH Group 1 in any of the following subtypes:

• Idiopathic PAH

• Heritable PAH

• Drug/toxin-induced PAH

• PAH associated with CTD

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

3. Symptomatic PAH classified as WHO FC III or IV

4. REVEAL Lite 2 risk score of ≥ 10

5. Right heart catheterization performed during screening (or within 2 weeks prior to screening, if done at the clinical study site) documenting a minimum PVR of ≥ 5 Wood units and a pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) of ≤ 15 mmHg

6. Clinically stable and on stable doses of maximum tolerated (per investigator's judgment) double or triple background PAH therapies for at least 30 days prior to screening

7. Females of childbearing potential must:

• Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting study therapy; 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

• 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

• 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

8. Male participants must:

• 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

• 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

9. Ability to adhere to study visit schedule and understand and comply with all protocol requirements

10. Ability to understand and provide written informed consent

Exclusion Criteria:

1. Diagnosis of PAH WHO Groups 2, 3, 4, or 5

2. Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus-associated PAH and PAH associated with portal hypertension

3. Diagnosis of pulmonary veno-occlusive diseases or pulmonary capillary hemangiomatosis or overt signs of capillary and/or venous involvement

4. Hemoglobin at screening above gender-specific upper limit of normal (ULN), per local laboratory test

5. Baseline platelet count < 50,000/mm3 (< 50.0 x 109/L) at screening

6. Baseline systolic blood pressure < 85 mmHg at screening

7. Pregnant or breastfeeding women

8. Any of the following clinical laboratory values at the Screening Visit:

• Estimated glomerular filtration rate < 30 mL/min/m2 (as defined by the Modification of Diet in Renal Disease Study equation)

• Serum alanine aminotransferase or aspartate aminotransferase levels > 3 × ULN or total bilirubin > 2.0 × ULN

9. 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

10. Prior exposure to or known allergic reaction to sotatercept (ACE 011) or luspatercept (ACE-536)

11. History of pneumonectomy

12. Pulmonary function test values of forced vital capacity < 60% predicted within 1 year prior to the Screening Visit

13. Untreated obstructive sleep apnea

14. History of known pericardial constriction

15. History of restrictive or congestive cardiomyopathy

16. Electrocardiogram (ECG) with Fridericia's corrected QT interval (QTcF) > 450 ms (or > 500 ms if right bundle branch block is present) during the Screening Period

17. Personal or family history of long QT syndrome or sudden cardiac death

18. Left ventricular ejection fraction < 50% on historical echocardiogram within 1 year prior to the Screening Visit

19. 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

20. Cerebrovascular accident within 3 months prior to the Screening Visit

21. Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease