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 objectives of this study are to evaluate the efficacy and safety of sotatercept treatment (plus background PAH therapy) versus placebo (plus background PAH therapy) at 24 weeks in adults with PAH.

Official Title

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Compare the Efficacy and Safety of Sotatercept Versus Placebo When Added to Background Pulmonary Arterial Hypertension (PAH) Therapy for the Treatment of PAH

Details

This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter, parallel-group study in subjects with symptomatic Pulmonary Arterial Hypertension (PAH) who present with idiopathic or heritable PAH, PAH associated with connective tissue diseases (CTD), drug or toxin induced, post shunt correction PAH, or PAH presenting at least 1 year following the correction of congenital heart defects (CHDs), and currently on background PAH therapy. The primary efficacy endpoint of the study is exercise capacity, as measured by the 6-minute walk distance (6MWD) measured at 24 week following initiation of treatment. Approximately 284 participants will be enrolled and randomized 1:1 to receive either sotatercept or placebo on the background of stable standard-of-care PAH mediation. Study duration will be approximately 2 years A stratified Wilcoxon test will be used for analysis of the primary endpoint, with appropriate imputation for missing data, as detailed in the Statistical Analysis Plan. An unblinded, external, independent Data Monitoring Committee (DMC) will monitor participant safety throughout the course of the study. Participants completing this study will be eligible to receive sotatercept in a separate, open-label extension study.

Keywords

Pulmonary Arterial Hypertension Pulmonary Hypertension sotatercept Familial Primary Pulmonary Hypertension Sotatercept plus background PAH theraphy

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Age ≥ 18 years
  2. Documented diagnostic right heart catheterization (RHC) at any time prior to screening confirming the diagnosis of WHO pulmonary arterial hypertension (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 Functional Class II or III
  9. Baseline RHC performed during the Screening Period documenting a minimum pulmonary vascular resistance (PVR) of ≥ 5 Wood units (WU) and a pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure of ≤ 15 mmHg.
  10. On stable doses of background PAH therapy and diuretics (i.e., patient-specific dose goal for each therapy already achieved) for at least 90 days prior to screening; for infusion prostacyclins, dose adjustment within 10% of optimal dose is allowed per medical practice.
  11. 6MWD ≥ 150 and ≤ 500 m repeated twice at screening (measured at least 4 hours apart, but no longer than 1 week), and both values are within 15% of each other (calculated from the highest value)
  12. Females of childbearing potential must:
  13. Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting study therapy; she must agree to ongoing urine or serum pregnancy testing during 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:
  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...

  1. Diagnosis of pulmonary hypertension 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. Exclusions in PAH Group I should also include schistosomiasis APAH and pulmonary veno occlusive disease
  3. Hemoglobin (Hgb) at screening above gender-specific upper limit of normal (ULN), per local laboratory test
  4. Baseline platelet count < 50,000/mm3 (< 50.0 x 109/L) at screening
  5. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure > 160 mmHg or sitting diastolic blood pressure > 100 mmHg during screening visit after a period of rest
  6. Baseline systolic BP < 90 mmHg at screening
  7. Pregnant or breastfeeding women
  8. Any of the following clinical laboratory values at the screening visit:
  9. Estimated glomerular filtration rate (eGFR) < 30 mL/min/m2 (as defined by MDRD equation)
  10. Serum alanine aminotransferase, aspartate aminotransferase, or total bilirubin levels > 3 × ULN (bilirubin criterion waived if there is a documented history of Gilbert's syndrome)
  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. . Prior exposure to sotatercept (ACE-011) or luspatercept (ACE 536) and/or excipients or known allergic reaction to either one
  13. . Have full or partial pneumonectomy
  14. . Pulmonary function test (PFT) values of forced vital capacity (FVC) < 60% predicted at the screening visit or within 6 months prior to the screening visit. If PFT is not available, a chest CT scan showing more than mild interstitial lung disease (ILD) performed at the screening visit or 1 year prior to it.
  15. . 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).
  16. . History of more than mild obstructive sleep apnea that is untreated
  17. . Known history of portal hypertension or chronic liver disease, including hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication), defined as mild to severe hepatic impairment (Child-Pugh Class A-C)
  18. . History of restrictive, constrictive or congestive cardiomyopathy
  19. . History of atrial septostomy within 180 days prior to the screening visit
  20. . Electrocardiogram (ECG) with Fridericia's corrected QT interval (QTcF) > 500 ms during the screening period
  21. . Personal or family history of long QT syndrome (LQTS) or sudden cardiac death
  22. . Left ventricular ejection fraction < 45% on historical echocardiogram within 6 months prior to the screening visit
  23. . Any symptomatic coronary disease events within 6 months (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) within 6 months of the screening visit. Note: Anginal pain can be ignored as an exclusion criterion if coronary angiography shows no obstructions.
  24. . Cerebrovascular accident within 3 months prior to the screening visit
  25. . Acutely decompensated heart failure within 30 days prior to the screening visit, as per investigator assessment
  26. . Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease
  27. . Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to the screening visit

Locations

  • University of California San Diego Medical Center
    La Jolla California 92093 United States
  • Lundquist Institute For Biomedical Innovation At Harbor Ucla
    Torrance California 90502 United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Acceleron Pharma Inc.
ID
NCT04576988
Phase
Phase 3 research study
Study Type
Interventional
Participants
Expecting 284 study participants
Last Updated