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

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ClinicalTrials.gov Identifier: NCT03496207
Recruitment Status : Active, not recruiting
First Posted : April 12, 2018
Last Update Posted : August 28, 2019
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Drug: Placebo Drug: Sotatercept Phase 2

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: 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)
Actual Study Start Date : June 27, 2018
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : November 2021


Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo SC every 21 days plus SOC for 24 weeks
Drug: Placebo
Placebo

Experimental: Sotatercept 0.3 mg/kg
Sotatercept, 0.3 mg/kg SC every 21 days plus SOC for 24 weeks
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
Other Name: ACE-011

Experimental: Sotatercept 0.7 mg/kg
Sotatercept, 0.7 mg/kg SC every 21 days plus SOC for 24 weeks
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
Other Name: ACE-011




Primary Outcome Measures :
  1. Change from baseline in Pulmonary Vascular Resistance (PVR) as measured by right heart catheterization [ Time Frame: From initiation of treatment (Study Day 1) to end of placebo-controlled treatment period (Study Day 168) ]

Secondary Outcome Measures :
  1. Change from baseline in 6-Minute Walk Distance (6MWD) [ Time Frame: From initiation of treatment (Study Day 1) to end of placebo-controlled treatment period (Study Day 168) ]
  2. Change from baseline in amino-terminal brain natriuretic propeptide (NT-proBNP) [ Time Frame: From initiation of treatment (Study Day 1) to end of placebo-controlled treatment period (Study Day 168) ]
  3. Change from baseline in tricuspid annular plane systolic excursion (TAPSE) by echocardiography (ECHO) [ Time Frame: From initiation of treatment (Study Day 1) to end of placebo-controlled treatment period (Study Day 168) ]
  4. Change from baseline in Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) patient-reported outcome (PRO) score [ Time Frame: From initiation of treatment (Study Day 1) to end of placebo-controlled treatment period (Study Day 168) ]
    The CAMPHOR questionnaire contains 65 items in total, 25 relating to symptoms, 15 relating to activities, and 25 relating to Quality of Life (QoL). It is negatively weighted; a higher score indicates worse QoL and greater functional limitation. Symptom and QoL items are both scored out of 25: "yes/true" scores 1 and "no/not true" scores 0. Activity items have three possible responses (score 0-2), giving a score out of 30.

  5. Change from baseline in 36-Item Short Form Health Survey (SF-36) patient-reported outcome (PRO) score [ Time Frame: From initiation of treatment (Study Day 1) to end of placebo-controlled treatment period (Study Day 168) ]
    The SF-36 questionnaire is a 36-item, patient-reported survey of patient health. The questionnaire consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

    • Idiopathic
    • Heritable PAH
    • Drug- or toxin-induced PAH
    • PAH associated with connective tissue disease
    • 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. 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
  9. Systolic BP < 90 mmHg during Screening or at baseline
  10. History of known pericardial constriction
  11. Personal or family history of long QTc syndrome or sudden cardiac death
  12. History of restrictive or congestive cardiomyopathy
  13. 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.
  14. 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)
  15. Acutely decompensated heart failure within 30 days prior to study visit C1D1, as per investigator assessment
  16. Significant (≥ 2+ regurgitation) mitral regurgitation (MR) or aortic regurgitation (AR) valvular disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03496207


  Hide Study Locations
Locations
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United States, Arizona
Pulmonary Associates, PA
Phoenix, Arizona, United States, 85006
Arizona Pulmonary Specialists
Phoenix, Arizona, United States, 85012
Banner-University Medical Center Phoenix
Phoenix, Arizona, United States, 85381
University of Arizona
Tucson, Arizona, United States, 85724
United States, California
University of California, San Francisco Medical Center
San Francisco, California, United States, 94143
United States, Colorado
University of Colorado Hospital
Aurora, Colorado, United States, 80045
United States, Florida
UF Health Shands Hospital
Gainesville, Florida, United States, 32610
Cleveland Clinic Florida
Weston, Florida, United States, 33331
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Center for Outpatient Health
Saint Louis, Missouri, United States, 63110
United States, Ohio
Lindner Clinical Trial Center
Cincinnati, Ohio, United States, 45129
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
Houston Methodist Hospital
Houston, Texas, United States, 77030
Australia, New South Wales
St. Vincent's Hospital Sydney
Darlinghurst, New South Wales, Australia, 2010
Westmead Hospital
Westmead, New South Wales, Australia, 2145
Australia, New South Whales
John Hunter Hospital
New Lambton, New South Whales, Australia, 2305
Australia, Queensland
Prince Charles Hospital
Chermside, Queensland, Australia, 4032
Australia, Western Australia
Fiona Stanley Hospital
Murdoch, Western Australia, Australia, 6150
Brazil
Hospital Madre Teresa
Belo Horizonte, Minas Gerais, Brazil, 30430
Irmandade Da Santa Casa de Misericordia de Porto Alegre
Porto Alegre, Riogrande Do Sul, Brazil, 90035
Hospital Dia do Pulmão
Blumenau, Santa Catarina, Brazil, 89010
Hospital São Paulo
Sao Paulo, Brazil, 04037
France
Hôpital Arnaud de Villeneuve
Montpellier, Hérault, France, 34295
Centre Hospitalier Universitaire de Bicêtre
Le Kremlin-Bicêtre, France, 94275
Centre Hospitalier Universitaire de Saint Etienne
Saint-Étienne, France, 42055
Germany
Klinikum der Universität Regensburg
Regensburg, Bayern,, Germany, 93053
Medizinische Hochschule Hannover
Hannover, Niedersachsen, Germany, 30625
Universitatsklinikum Halle (Saale)
Halle, Sachsen-Anhalt, Germany, 06120
Otto-von-Guericke-Universität Magdeburg
Magdeburg, Sachsen-Anhalt, Germany, 39120
Universitatsklinikum Leipzig
Leipzig, Sachsen, Germany, 04103
DRK Kliniken Berlin Westend
Berlin, Germany, 14050
Israel
Barzilai Medical Center
Ashkelon, Israel, 78278
Lady Davis Carmel Medical Center
Haifa, Israel, 34362
Rabin Medical Center - PPDS
Petach-Tikva, Israel, 49100
ZIV Medical Center
Safed, Israel, 13100
Spain
Hospital Universitario Marques de Valdecilla
Santander, Cantabria, Spain, 39008
Hospital Universitario Puerta de Hierro-Majadahonda
Majadahonda, Madrid, Spain, 28222
Hospital Complejo Hospitalario Universitario de Pontevedra
Santander, Pontevedra, Spain, 36071
Hospital Universitario Vall d'Hebron - PPDS
Barcelona, Spain, 08035
Hospital Clinic de Barcelona
Barcelona, Spain, 08036
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Hospital de Montecel
Pontevedra, Spain, 36071
United Kingdom
Royal Free London NHS Foundation Trust
London, United Kingdom, NW32QG
Sponsors and Collaborators
Acceleron Pharma, Inc.

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Responsible Party: Acceleron Pharma, Inc.
ClinicalTrials.gov Identifier: NCT03496207     History of Changes
Other Study ID Numbers: A011-09
2017-004738-27 ( EudraCT Number )
First Posted: April 12, 2018    Key Record Dates
Last Update Posted: August 28, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Acceleron Pharma, Inc.:
PAH
Additional relevant MeSH terms:
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Familial Primary Pulmonary Hypertension
Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases