Trial record 2 of 2 for:
sotatercept | Pulmonary Arterial Hypertension
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:
Acceleron Pharma, Inc.
Information provided by (Responsible Party):
Acceleron Pharma, Inc.
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 |
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 : | 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 |
Resource links provided by the National Library of Medicine
| 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 :
- 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 :
- 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.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Age ≥ 18 years
-
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
- Symptomatic pulmonary hypertension classified as WHO functional class II or III
- Screening RHC documenting a minimum PVR of ≥ 400 dyn·sec/cm5 (5 Wood units)
-
Pulmonary function tests (PFTs) within 6 months prior to Screening as follows:
- 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
- Forced expiratory volume (first second) (FEV1)/ forced vital capacity (FVC) > 70% predicted
- 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),
- No contraindication per investigator for RHC during the study
- 6MWD ≥ 150 and ≤ 550 meters repeated twice at Screening and both values within 15% of each other, calculated from the highest value
- PAH therapy at stable (per investigator) dose levels of SOC therapies
Exclusion Criteria:
- Stopped receiving any pulmonary hypertension chronic general supportive therapy (e.g, diuretics, oxygen, anticoagulants, digoxin) within 60 days prior to study visit C1D1
- Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to study visit C1D1
- History of atrial septostomy within 180 days prior to Screening
- History of more than mild obstructive sleep apnea that is untreated
- 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)
- History of human immunodeficiency virus infection-associated PAH
- Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536)
- 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
- Systolic BP < 90 mmHg during Screening or at baseline
- History of known pericardial constriction
- Personal or family history of long QTc syndrome or sudden cardiac death
- History of restrictive or congestive cardiomyopathy
- 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.
- 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)
- Acutely decompensated heart failure within 30 days prior to study visit C1D1, as per investigator assessment
- 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
Locations
Show 44 study locations
Sponsors and Collaborators
Acceleron Pharma, Inc.
| Responsible Party: | Acceleron Pharma, Inc. |
| ClinicalTrials.gov Identifier: | NCT03496207 |
| 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 |
| 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:
|
Familial Primary Pulmonary Hypertension Hypertension Vascular Diseases Cardiovascular Diseases |
Hypertension, Pulmonary Lung Diseases Respiratory Tract Diseases |