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Trial record 7 of 19 for:    PULSAR

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

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ClinicalTrials.gov Identifier: NCT03496207
Recruitment Status : Recruiting
First Posted : April 12, 2018
Last Update Posted : May 23, 2018
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 double-blind 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 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 1:1:1 ratio to receive sotatercept 0.3 mg/kg subcutaneously (SC) every 21 days, sotatercept 0.7 mg/kg SC every 21 days, or placebo every 21 days for a period of 24 weeks in the double-blind 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 Treatment Period and have had their post-Treatment Period PVR assessment will be eligible (per investigator assessment) 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 will be 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 : Interventional  (Clinical Trial)
Estimated Enrollment : 90 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)
Estimated Study Start Date : June 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 double-blind 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 double-blind 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 double-blind 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 double-blind 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 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.

  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 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.



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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 or 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 60-70% predicted, confirmatory high-resolution computed tomography indicating no more than mild interstitial lung disease (ILD)
    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), any time prior to Screening with normal or low probability result
  7. No contraindication per investigator for RHC during the study
  8. 6MWD ≥ 150 and ≤ 450 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. Systolic BP < 90 mmHg during Screening or at baseline
  9. History of known pericardial constriction
  10. History of restrictive or congestive cardiomyopathy
  11. Left ventricular ejection fraction (LVEF) < 45% on echocardiogram (ECHO) or pulmonary capillary wedge pressure (PCWP) > 15 mmHg on right heart catheterization during baseline evaluation
  12. 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)
  13. Acutely decompensated heart failure within 30 days prior to study visit C1D1, as per investigator assessment
  14. 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


Contacts
Contact: Clinical Trial Manager 617-649-9200 clinicaltrials011@acceleronpharma.com

Locations
United States, Arizona
Pulmonary Associates, PA Recruiting
Phoenix, Arizona, United States, 85006
Contact: LiYi Lu       palyf@aol.com   
Principal Investigator: David Baratz, MD         
Sponsors and Collaborators
Acceleron Pharma, Inc.

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: May 23, 2018
Last Verified: May 2018

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:
Hypertension
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases