Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at La Jolla, California and other locations
Dates
study started
estimated completion

Description

Summary

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.

Official Title

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate Sotatercept When Added to Background Pulmonary Arterial Hypertension (PAH) Therapy in Newly Diagnosed Intermediate- and High-risk PAH Patients

Details

Study A011-13 is Phase 3, randomized, double-blind, placebo-controlled study to evaluate sotatercept when added to background PAH therapy in newly diagnosed intermediate- or high risk PAH patients. Participants enrolled in the study will have a diagnosis within 6 months of study screening of symptomatic PAH (WHO Group 1, classified as FC II or III) and presentation of idiopathic or heritable PAH, PAH associated with connective tissue diseases (CTD), drug- or toxin- induced PAH, post shunt correction PAH, or PAH presenting at least 1 year following the correction of congenital heart defects.

Keywords

Pulmonary Arterial Hypertension Pulmonary Hypertension Sotatercept Familial Primary Pulmonary Hypertension Sotatercept plus background PAH therapy

Eligibility

You can join if…

Open to people ages 18 years and up

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:
  3. Idiopathic PAH
  4. Heritable PAH
  5. Drug/toxin-induced PAH
  6. PAH associated with connective tissue disease
  7. PAH associated with simple, congenital systemic to pulmonary shunts at least 1 year following repair
  8. Symptomatic PAH classified as WHO FC II or III
  9. REVEAL Lite 2 Risk Score ≥ 6
  10. 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.
  11. 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)
  12. Females of childbearing potential must meet the following criteria:
  13. 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
  14. 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
  15. 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
  16. Male participants must meet the following criteria:
  17. 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
  18. 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
  19. Ability to adhere to study visit schedule and understand and comply with all protocol requirements
  20. . Ability to understand and provide written informed consent

You CAN'T join if...

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:
  8. Estimated glomerular filtration rate < 30 mL/min/m2 (as defined by MDRD equation)
  9. Serum alanine aminotransferase or aspartate aminotransferase levels > 3 × ULN or total bilirubin > 1.5 × ULN
  10. Platelet count < 50,000/mm3 (< 50.0 × 109 /L)
  11. 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
  12. Known allergic reaction to sotatercept (ACE-011)
  13. . History of pneumonectomy
  14. . Pulmonary function test values of forced vital capacity < 60% predicted within 1 year prior to the Screening Visit
  15. . Stopped receiving any pulmonary hypertension chronic general supportive therapy (e.g., diuretics, oxygen, anticoagulants, and digoxin) within 60 days prior to the Screening Visit
  16. . 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)
  17. . Untreated obstructive sleep apnea
  18. . History of known pericardial constriction
  19. . History of restrictive or congestive cardiomyopathy
  20. . History of atrial septostomy within 180 days prior to the Screening Visit
  21. . 18. Electrocardiogram with Fridericia's corrected QT interval > 450 ms (or > 500 ms if right bundle branch abnormality is present) during the Screening Period
  22. . Personal or family history of long QT syndrome or sudden cardiac death
  23. . 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
  24. . 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
  25. . Cerebrovascular accident within 3 months prior to the Screening Visit
  26. . Acutely decompensated heart failure within 30 days prior to the Screening Visit, as per investigator assessment
  27. . Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease
  28. . Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, and vasopressin) within 30 days prior to the Screening Visit

Locations

  • University of California San Diego ( Site 1002) accepting new patients
    La Jolla California 92037 United States
  • University of California Irvine ( Site 1086) accepting new patients
    Orange California 92868 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
ID
NCT04811092
Phase
Phase 3 research study
Study Type
Interventional
Participants
Expecting 662 study participants
Last Updated