A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (STELLAR)

  • STATUS
    Recruiting
  • End date
    Dec 24, 2022
  • participants needed
    284
  • sponsor
    Acceleron Pharma Inc.
Updated on 24 September 2021

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.

Description

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.

Details
Condition Pulmonary Arterial Hypertension
Treatment Placebo, Sotatercept
Clinical Study IdentifierNCT04576988
SponsorAcceleron Pharma Inc.
Last Modified on24 September 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Age 18 years
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
Idiopathic PAH
Heritable PAH
Drug/toxin-induced PAH
PAH associated with connective tissue disease
PAH associated with simple, congenital systemic to pulmonary shunts at least 1 year following repair
Symptomatic PAH classified as WHO Functional Class II or III
Baseline RHC performed during the Screening Period documenting a minimum pulmonary vascular resistance (PVR) of 5 Wood units (WU)
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. Background PAH therapy is defined in Section 7.2
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)
Females of childbearing potential must
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
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
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
Ability to adhere to study visit schedule and understand and comply with all protocol requirements
Ability to understand and provide written informed consent

Exclusion Criteria

Diagnosis of pulmonary hypertension WHO Groups 2, 3, 4, or 5
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
Hemoglobin (Hgb) at screening above gender-specific upper limit of normal (ULN), per local laboratory test
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
Baseline systolic BP < 90 mmHg at screening
Pregnant or breastfeeding women
Any of the following clinical laboratory values at the screening visit
Estimated glomerular filtration rate (eGFR) < 30 mL/min/m2 (as defined by MDRD equation)
Serum alanine aminotransferase or aspartate aminotransferase levels > 3 ULN or total bilirubin > 1.5 ULN
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
Prior exposure to sotatercept (ACE-011) or luspatercept (ACE 536) and/or excipients or known allergic reaction to either one
Have full or partial pneumonectomy
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 no more than mild interstitial lung disease (ILD) performed at the screening visit or 1 year to it
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)
History of more than mild obstructive sleep apnea that is untreated
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)
History of restrictive, constrictive or congestive cardiomyopathy
History of atrial septostomy within 180 days prior to the screening visit
Electrocardiogram (ECG) with Fridericia's corrected QT interval (QTcF) > 500 ms during the screening period
Personal or family history of long QT syndrome (LQTS) or sudden cardiac death
Left ventricular ejection fraction < 45% on historical echocardiogram within 6 months prior to the screening visit or pulmonary capillary wedge pressure > 15 mmHg as determined in the Screening Period RHC
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
Cerebrovascular accident within 3 months prior to the screening visit
Acutely decompensated heart failure within 30 days prior to the screening visit, as per investigator assessment
Significant ( 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease, mitral stenosis and more than mild aortic valve stenosis
Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to the screening visit
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