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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

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: i. 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. 3. Symptomatic pulmonary hypertension classified as WHO functional class II or
  • III. 4.
Screening RHC documenting a minimum PVR of ≥ 400 dyn·sec/cm5 (5 Wood units) 5. Pulmonary function tests (PFTs) within 6 months prior to Screening as follows: 1. 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. 2. Forced expiratory volume (first second) (FEV1)/ forced vital capacity (FVC) > 70% predicted. 6. 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), 7. No contraindication per investigator for RHC during the study. 8. 6MWD ≥ 150 and ≤ 550 meters repeated twice at Screening and both values within 15% of each other, calculated from the highest value. 9. PAH therapy at stable (per investigator) dose levels of SOC therapies.

Exclusion Criteria:

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. 21. 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. 22. History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant proteins or excipients in the investigational product. 23. Major surgery within 8 weeks prior to C1D1. Participants must have completely recovered from any previous surgery prior to C1D1. 24. Prior heart or heart-lung transplants or life expectancy of < 12 month. 25. Pregnant or breastfeeding females. 26. 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. 27. 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. 28. 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. 29. 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. 30. Weight > 140 kg at Screening

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03496207
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Acceleron Pharma Inc.
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Active, not recruiting
Countries Australia, Brazil, France, Germany, Israel, Spain, United Kingdom, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Pulmonary Arterial Hypertension
Additional 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.

Arms & Interventions

Arms

Placebo Comparator: Placebo

Placebo SC every 21 days plus SOC for 24 weeks

Experimental: Sotatercept 0.3 mg/kg

Sotatercept, 0.3 mg/kg SC every 21 days plus SOC for 24 weeks

Experimental: Sotatercept 0.7 mg/kg

Sotatercept, 0.7 mg/kg SC every 21 days plus SOC for 24 weeks

Interventions

Drug: - Placebo

Placebo

Drug: - Sotatercept

Sotatercept (ACE-011) is a recombinant fusion protein consisting of the extracellular domain of the human activin receptor type IIA linked to the Fc piece of human IgG1

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Pulmonary Associates, PA, Phoenix, Arizona

Status

Address

Pulmonary Associates, PA

Phoenix, Arizona, 85006

Arizona Pulmonary Specialists, Phoenix, Arizona

Status

Address

Arizona Pulmonary Specialists

Phoenix, Arizona, 85012

Banner-University Medical Center Phoenix, Phoenix, Arizona

Status

Address

Banner-University Medical Center Phoenix

Phoenix, Arizona, 85381

University of Arizona, Tucson, Arizona

Status

Address

University of Arizona

Tucson, Arizona, 85724

San Francisco, California

Status

Address

University of California, San Francisco Medical Center

San Francisco, California, 94143

University of Colorado Hospital, Aurora, Colorado

Status

Address

University of Colorado Hospital

Aurora, Colorado, 80045

UF Health Shands Hospital, Gainesville, Florida

Status

Address

UF Health Shands Hospital

Gainesville, Florida, 32610

University of Kansas Medical Center, Kansas City, Kansas

Status

Address

University of Kansas Medical Center

Kansas City, Kansas, 66160

University of Michigan, Ann Arbor, Michigan

Status

Address

University of Michigan

Ann Arbor, Michigan, 48109

Lindner Clinical Trial Center, Cincinnati, Ohio

Status

Address

Lindner Clinical Trial Center

Cincinnati, Ohio, 45129

Medical University of South Carolina, Charleston, South Carolina

Status

Address

Medical University of South Carolina

Charleston, South Carolina, 29425

Houston Methodist Hospital, Houston, Texas

Status

Address

Houston Methodist Hospital

Houston, Texas, 77030

International Sites

St. Vincent's Hospital Sydney, Darlinghurst, New South Wales, Australia

Status

Address

St. Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010

Westmead Hospital, Westmead, New South Wales, Australia

Status

Address

Westmead Hospital

Westmead, New South Wales, 2145

John Hunter Hospital, New Lambton, New South Whales, Australia

Status

Address

John Hunter Hospital

New Lambton, New South Whales, 2305

Prince Charles Hospital, Chermside, Queensland, Australia

Status

Address

Prince Charles Hospital

Chermside, Queensland, 4032

Hospital Madre Teresa, Belo Horizonte, Minas Gerais, Brazil

Status

Address

Hospital Madre Teresa

Belo Horizonte, Minas Gerais, 30430

Porto Alegre, Riogrande Do Sul, Brazil

Status

Address

Irmandade Da Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Riogrande Do Sul, 90035

Hospital Dia do Pulmão, Blumenau, Santa Catarina, Brazil

Status

Address

Hospital Dia do Pulmão

Blumenau, Santa Catarina, 89010

Instituto do Coracao - HCFMUSP, Cerqueira César, Brazil

Status

Address

Instituto do Coracao - HCFMUSP

Cerqueira César, , 05403-900

Hospital Sao Lucas da PUCRS, Jardim Botânico, Brazil

Status

Address

Hospital Sao Lucas da PUCRS

Jardim Botânico, , 05403-900

Hospital São Paulo, Sao Paulo, Brazil

Status

Address

Hospital São Paulo

Sao Paulo, , 04037

Hôpital Arnaud de Villeneuve, Montpellier, Hérault, France

Status

Address

Hôpital Arnaud de Villeneuve

Montpellier, Hérault, 34295

CHU Michallon, La Tronche, France

Status

Address

CHU Michallon

La Tronche, , 38700

Le Kremlin-Bicêtre, France

Status

Address

Centre Hospitalier Universitaire de Bicêtre

Le Kremlin-Bicêtre, , 94275

Saint-Étienne, France

Status

Address

Centre Hospitalier Universitaire de Saint Etienne

Saint-Étienne, , 42055

Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Status

Address

Medizinische Hochschule Hannover

Hannover, Niedersachsen, 30625

Universitatsklinikum Halle (Saale), Halle, Sachsen-Anhalt, Germany

Status

Address

Universitatsklinikum Halle (Saale)

Halle, Sachsen-Anhalt, 06120

Universitatsklinikum Leipzig, Leipzig, Sachsen, Germany

Status

Address

Universitatsklinikum Leipzig

Leipzig, Sachsen, 04103

Dresden, Germany

Status

Address

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, , 01307

Barzilai Medical Center, Ashkelon, Israel

Status

Address

Barzilai Medical Center

Ashkelon, , 78278

Lady Davis Carmel Medical Center, Haifa, Israel

Status

Address

Lady Davis Carmel Medical Center

Haifa, , 34362

Meir Medical Center, Kefar Sava, Israel

Status

Address

Meir Medical Center

Kefar Sava, , 4428100

Rabin Medical Center - PPDS, Petach-Tikva, Israel

Status

Address

Rabin Medical Center - PPDS

Petach-Tikva, , 49100

Chaim Sheba Medical Center, Ramat Gan, Israel

Status

Address

Chaim Sheba Medical Center

Ramat Gan, , 52621

Santander, Cantabria, Spain

Status

Address

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008

Majadahonda, Madrid, Spain

Status

Address

Hospital Universitario Puerta de Hierro-Majadahonda

Majadahonda, Madrid, 28222

Barcelona, Spain

Status

Address

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, , 08035

Hospital Clinic de Barcelona, Barcelona, Spain

Status

Address

Hospital Clinic de Barcelona

Barcelona, , 08036

Hospital Universitario 12 de Octubre, Madrid, Spain

Status

Address

Hospital Universitario 12 de Octubre

Madrid, , 28041

Golden Jubilee National Hospital - PPDS, Clydebank, United Kingdom

Status

Address

Golden Jubilee National Hospital - PPDS

Clydebank, , G81 4DY

Royal Free London NHS Foundation Trust, London, United Kingdom

Status

Address

Royal Free London NHS Foundation Trust

London, , NW32QG

Imperial College Healthcare NHS Trust, London, United Kingdom

Status

Address

Imperial College Healthcare NHS Trust

London, , W2 1NY

For more information, please contact PHA at Research@PHAssociation.org and refer to the terms of service below.

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