Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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.

Tracking Information
First Submitted Date  ICMJE March 29, 2018
First Posted Date  ICMJE April 12, 2018
Last Update Posted Date August 28, 2019
Actual Study Start Date  ICMJE June 27, 2018
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 26, 2018)
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) ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 11, 2018)
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 double-blind treatment period (Study Day 168) ]
Change History Complete list of historical versions of study NCT03496207 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 26, 2018)
  • 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) ]
  • 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) ]
  • 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) ]
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 11, 2018)
  • Change from baseline in 6-Minute Walk Distance (6MWD) [ Time Frame: From initiation of treatment (Study Day 1) to end of double-blind treatment period (Study Day 168) ]
  • Change from baseline in amino-terminal brain natriuretic propeptide (NT-proBNP) [ Time Frame: From initiation of treatment (Study Day 1) to end of double-blind treatment period (Study Day 168) ]
  • 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 double-blind treatment period (Study Day 168) ]
  • 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 double-blind 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.
  • 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 double-blind 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Sotatercept for the Treatment of Pulmonary Arterial Hypertension (PAH)
Official Title  ICMJE 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)
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Pulmonary Arterial Hypertension
Intervention  ICMJE
  • 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
    Other Name: ACE-011
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo SC every 21 days plus SOC for 24 weeks
    Intervention: Drug: Placebo
  • Experimental: Sotatercept 0.3 mg/kg
    Sotatercept, 0.3 mg/kg SC every 21 days plus SOC for 24 weeks
    Intervention: Drug: Sotatercept
  • Experimental: Sotatercept 0.7 mg/kg
    Sotatercept, 0.7 mg/kg SC every 21 days plus SOC for 24 weeks
    Intervention: Drug: Sotatercept
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: February 22, 2019)
100
Original Estimated Enrollment  ICMJE
 (submitted: April 11, 2018)
90
Estimated Study Completion Date  ICMJE November 2021
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Brazil,   France,   Germany,   Israel,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03496207
Other Study ID Numbers  ICMJE A011-09
2017-004738-27 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Acceleron Pharma, Inc.
Study Sponsor  ICMJE Acceleron Pharma, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Acceleron Pharma, Inc.
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP