Summary

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

Description

Summary

Study A011-09 is designed to assesses the efficacy and safety of sotatercept (ACE-011) relative to placebo in adults with pulmonary arterial hypertension (PAH). Eligible participants will receive study treatment for 6 months in the Placebo-Controlled Treatment Period, and then will be eligible to enroll into an 18- month Extension Period during which all participants will receive sotatercept. All treated patients will be also undergo follow-up period after last study drug treatment.

Official Title

A Phase 2, Double-Blind, Placebo-Controlled, Randomized Study to Compare the Efficacy and Safety of Sotatercept (ACE-011) Versus Placebo When Added to Standard of Care for the Treatment of Pulmonary Arterial Hypertension (PAH)

Details

This is a Phase 2, double blind, randomized, placebo-controlled, parallel-group study of sotatercept plus SOC versus placebo plus SOC in participants with PAH of WHO Group 1, functional class II-III. Participants will be randomly assigned in a 3:3:4 ratio to receive placebo every 21 days, sotatercept 0.3 mg/kg subcutaneously (SC) every 21 days, or sotatercept 0.7 mg/kg SC every 21 days, for a period of 24 weeks in the Placebo-Controlled Treatment Period of the study while on standard of care therapy. Evaluations will include changes in pulmonary vascular resistance (PVR), six-minute-walk distance (6MWD), quality of life questionnaires, echocardiographic parameters, and safety. Participants who have not discontinued early from the Placebo-Controlled Treatment Period and have had their post-Treatment Period PVR assessment will be able to continue into the 18-month Extension Period in which sotatercept-treated participants will receive their latest dose level of sotatercept SC every 21 days and placebo-treated participants willbe re-randomized 1:1 to receive sotatercept 0.3 mg/kg SC every 21 days or sotatercept 0.7 mg/kg SC every 21 days while on standard of care therapy.

Keywords

Pulmonary Arterial Hypertension PAH Familial Primary Pulmonary Hypertension Hypertension Sotatercept Sotatercept 0.3 mg/kg Sotatercept 0.7 mg/kg

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 diagnosis of WHO diagnostic pulmonary hypertension Group I: PAH in any of the following subtypes:
  3. Idiopathic ii. Heritable PAH iii. Drug- or toxin-induced PAH iv. PAH associated with connective tissue disease v. PAH associated with simple, congenital systemic-to-pulmonary shunts at least 1 year following shunt repair
  4. Symptomatic pulmonary hypertension classified as WHO functional class II or III
  5. Screening RHC documenting a minimum PVR of ≥ 400 dyn·sec/cm5 (5 Wood units)
  6. Pulmonary function tests (PFTs) within 6 months prior to Screening as follows:
  7. Total lung capacity (TLC) > 70% predicted; or if between 60 to70% predicted, or not possible to be determined, confirmatory high-resolution computed tomography (CT) indicating no more than mild interstitial lung disease (ILD), per investigator interpretation, or
  8. Forced expiratory volume (first second) (FEV1)/ forced vital capacity (FVC) > 70% predicted
  9. Ventilation-perfusion (VQ) scan (or, if unavailable a negative CT pulmonary angiogram [CTPA] result, or pulmonary angiography result), any time prior to Screening Visit or conducted during the Screening Period, with normal or low probability result),
  10. No contraindication per investigator for RHC during the study
  11. 6MWD ≥ 150 and ≤ 550 meters repeated twice at Screening and both values within 15% of each other, calculated from the highest value
  12. PAH therapy at stable (per investigator) dose levels of SOC therapies

You CAN'T join if...

  1. Stopped receiving any pulmonary hypertension chronic general supportive therapy (e.g, diuretics, oxygen, anticoagulants, digoxin) within 60 days prior to study visit C1D1
  2. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to study visit C1D1
  3. History of atrial septostomy within 180 days prior to Screening
  4. History of more than mild obstructive sleep apnea that is untreated
  5. 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)
  6. History of human immunodeficiency virus infection-associated PAH
  7. Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536)
  8. Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to C1D1 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).
  9. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 160 mm Hg or sitting diastolic blood pressure > 100 mm Hg during Screening Visit after a period of rest
  10. . Systolic BP < 90 mmHg during Screening or at baseline
  11. . History of known pericardial constriction
  12. . Electrocardiogram (ECG) with Fridericia's corrected QT interval (QTcF) > 480 msec during Screening Period or C1D1
  13. . Personal or family history of long QTc syndrome or sudden cardiac death
  14. . Cerebrovascular accident within 3 months of C1D1
  15. . History of restrictive or congestive cardiomyopathy
  16. . Left ventricular ejection fraction (LVEF) < 45% on historical echocardiogram (ECHO) within 6 months prior to Screening Period (or done as a part of the Screening Period) or pulmonary capillary wedge pressure (PCWP) > 15 mmHg as determined in the Screening Period RHC.
  17. . 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)
  18. . Acutely decompensated heart failure within 30 days prior to study visit C1D1, as per investigator assessment
  19. . Significant (≥ 2+ regurgitation) mitral regurgitation (MR) or aortic regurgitation (AR) valvular disease
  20. . Any of the following clinical laboratory values during the Screening Period prior to

C1D1:

  1. Baseline Hgb > 16.0 g/dL
  2. Serum alanine aminotransferase or aspartate aminotransferase levels > 3X upper limit of normal (ULN) or total bilirubin > 1.5X ULN within 28 days of C1D1
  3. Estimated glomerular filtration rate < 30 ml/min/1.73m2 (4-variable Modification of Diet in Renal Disease equation) within 28 days of C1D1 or required renal replacement therapy within 90 days
  4. WBC count < 4000/mm3
  5. Platelets < 100,000/μL
  6. Absolute neutrophil count < 1500/mm3
  7. . History of opportunistic infection (e.g., invasive candidiasis or pneumocystis pneumonia) within 6 months prior to Screening; serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., septicemia) within 3 months prior to Screening
  8. . History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in the investigational product
  9. . Major surgery within 8 weeks prior to C1D1. Participants must have completely recovered from any previous surgery prior to C1D1.
  10. . Prior heart or heart-lung transplants or life expectancy of < 12 month
  11. . Pregnant or breastfeeding females
  12. . If on corticosteroids, and at any time in the last 30 days prior to the Screening

Period: have been receiving doses of > 20 mg/day of prednisone (or equivalent) or on a new or changing dose of ≤ 20 mg/day; only participants receiving stable doses of ≤ 20 mg prednisone (or equivalent) in last 30 days prior to the Screening Period permitted in the study

  1. . History of active malignancy, with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or ≤ 2 squamous cell carcinomas of the skin
  2. . History of clinically significant (as determined by the investigator) non-PAH related cardiac, endocrine, hematologic, hepatic, (auto)immune, metabolic, urologic, pulmonary, neurologic, neuromuscular, dermatologic, psychiatric, renal, and/or another disease that may limit participation in the study. Autoimmune diseases are excluded with the exception of those related to PAH etiologies included in this study.
  3. . Participation in another clinical trial involving intervention with another investigational drug, approved therapy for investigational use, or investigational device within 4 weeks prior to C1D1, or if the half-life of the previous product is known, within 5 times the half-life prior to C1D1, whichever is longer
  4. . Weight > 140 kg at Screening

Locations

  • University of California, San Francisco Medical Center
    San Francisco California 94143 United States
  • Banner-University Medical Center Phoenix
    Phoenix Arizona 85381 United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Acceleron Pharma Inc.
ID
NCT03496207
Phase
Phase 2
Study Type
Interventional
Last Updated