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临床试验/NCT03738150
NCT03738150已完成2 期

A Phase 2a Single-Arm, Open-Label, Multicenter Exploratory Study to Assess the Effects of Sotatercept (ACE-011) for the Treatment of Pulmonary Arterial Hypertension

Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA8 个研究点 分布在 1 个国家目标入组 21 人开始时间: 2019年4月19日最近更新:
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适应症

试验速览

阶段
2 期
状态
已完成
发起方
入组人数
21
试验地点
8
主要终点
Change From Baseline in Peak Oxygen Uptake (VO2 Max) at 24 Weeks
研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This study evaluates the effect of sotatercept (ACE-011) in adults with pulmonary arterial hypertension (PAH). Each eligible participant will receive standard of care (SOC) plus sotatercept (ACE-011) for a 24-week treatment period, followed by an 18-month extension period, and an 8-week follow-up period.

详细描述

This is a Phase 2a, single-arm, open-label, multicenter exploratory study to determine the effects of sotatercept plus SOC in adults with WHO functional class III PAH.

All eligible participants will receive SOC plus sotatercept at a starting dose level of 0.3 mg/kg by subcutaneous (SC) injection for Cycle 1 and escalating to 0.7 mg/kg at Cycle 2 for the remainder of the treatment period. Participants will be required to attend clinic visits once every three weeks for the 24-week treatment period and once every three weeks for the 18-month extension period to perform one or more protocol specified evaluations. Evaluations include hemodynamic measures collected during right heart catheterization (RHC) with invasive cardiopulmonary exercise test (iCPET), and cardiac magnetic resonance imaging (MR), 6-minute walk distance (6MWD), pharmacokinetic parameters, pharmacodynamic parameters, anti-drug antibody testing, and adverse events.

研究设计

研究类型
Interventional
分配方式
Na
干预模型
Single Group
主要目的
Treatment
盲法
None

入排标准

年龄范围
18 Years 至 —（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Age ≥ 18 years
  • •Documented findings on RHC at any time prior to Screening consistent with a diagnosis of World Health Organization (WHO) pulmonary hypertension Group 1: PAH of any of the following subtypes:
  • •Idiopathic PAH
  • •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 III
  • •Screening RHC documenting a minimum PVR of ≥ 4 Wood units
  • •Pulmonary function tests within 6 months prior to Screening as follows:
  • •Total lung capacity > 70% predicted; or if between 60% to 70% predicted, or not possible to be determined, confirmatory high-resolution computed tomography (CT) indicating no more than mild interstitial lung disease per investigator interpretation or
  • •Forced expiratory volume (first second) (FEV1)/forced vital capacity (FVC) > 70% predicted
  • •For subjects with a history of lobectomy or pneumonectomy, and for whom there are no population-based normalization methods, assessment based on residual lung volume will be permitted to assess eligibility.
  • •Ventilation-perfusion (VQ) scan (or, if unavailable, a negative CT pulmonary angiogram [CTPA] or pulmonary angiography result), any time prior to Screening or conducted during Screening Period with normal or low probability result
  • •6MWD ≥ 100 and ≤ 550 meters repeated twice during Screening Period and both values within 15% of each other, calculated from the highest value
  • •Combination PAH therapy at stable (per investigator) dose levels for at least 90 days prior to Cycle 1 Day 1 (C1D1)

排除标准

  • •Participants will be excluded from the study if they meet any of the following criteria:
  • •Started or stopped receiving any general supportive therapy for pulmonary hypertension (e.g., diuretics, oxygen, anticoagulants, digoxin) within 60 days prior to C1D1 (Cycle 1 Day 1)
  • •Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, vasopressin) within 30 days prior to C1D1
  • •History of atrial septostomy within 180 days prior to Screening
  • •History of more than mild obstructive sleep apnea that is untreated
  • •History of portal hypertension or chronic liver disease, defined as mild to severe hepatic impairment (Child-Pugh Classes A to 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 BP > 160 mm Hg or sitting diastolic BP > 100 mm Hg during Screening after a period of rest
  • •Systolic BP < 90 mm Hg during Screening or at baseline
  • •History of known pericardial constriction
  • •Electrocardiogram (ECG) with QTcF > 480 msec during Screening or C1D1
  • •History of personal or family history of long QTc syndrome or sudden cardiac death
  • •History of restrictive or constrictive cardiomyopathy
  • •Left ventricular ejection fraction < 45% on echocardiogram performed within 6 months of Screening OR pulmonary capillary wedge pressure (PCWP) > 15 mm Hg on RHC during baseline evaluation
  • •Any current symptomatic coronary disease (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain in the past 6 months prior to Screening)
  • •Acutely decompensated heart failure within 30 days prior to C1D1, as per investigator assessment
  • •Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease

结局指标

主要结局

Change From Baseline in Peak Oxygen Uptake (VO2 Max) at 24 Weeks

时间窗: Baseline and 24 weeks

Each participant's VO2 max was measured by an invasive cardiopulmonary exercise test (iCPET) at baseline and at 24 weeks.

次要结局

  • Change From Baseline in Arteriovenous O2 Content Difference (Ca-vO2) at 24 Weeks(Baseline and 24 weeks)
  • Change From Baseline in Right Ventricular Stroke Volume (RV SV) at 24 Weeks(Baseline and 24 weeks)
  • Change From Baseline in Right Ventricular End-Diastolic Volume (RV EDV) at 24 Weeks(Baseline and 24 weeks)
  • Change From Baseline in Concentration of Amino-Terminal Brain Natriuretic Propeptide (NT-proBNP) at 24 Weeks(Baseline and 24 Weeks)
  • Number of Participants With One or More Adverse Events (AEs)(Up to 24 weeks)
  • Change From Baseline in Right Ventricular (RV) Mass at 24 Weeks(Baseline and 24 weeks)
  • Change From Baseline in Cardiac Index at 24 Weeks(Baseline and 24 weeks)
  • Change From Baseline in Right Ventricular End-Systolic Volume (RV ESV) at 24 Weeks(Baseline and 24 weeks)
  • Percent Change From Baseline in Right Ventricular Ejection Fraction (RV EF) at 24 Weeks(Baseline and 24 Weeks)
  • Change From Baseline in Right Ventricular Stroke Volume Index (RV SVI) at 24 Weeks(Baseline and 24 weeks)
  • Change From Baseline in Ventilatory Efficiency (VE/VCO2 Slope) at 24 Weeks(Baseline and 24 weeks)
  • Change From Baseline in Mean Pulmonary Arterial Pressure at 24 Weeks(Baseline and 24 weeks)
  • Change From Baseline in Pulmonary Vascular Resistance (PVR) at 24 Weeks(Baseline and 24 weeks)
  • Change From Baseline in WHO (World Health Organization) Functional Class at 24 Weeks(Baseline and 24 Weeks)
  • Change From Baseline in 6-Minute Walk Distance (6MWD) at 24 Weeks(Baseline and 24 weeks)
  • Number of Participants Who Experienced One or More Events Indicative of Clinical Worsening of Pulmonary Arterial Hypertension (PAH)(Up to 102 weeks)
  • Observed Trough Concentration (Ctrough) of Sotatercept at Cycle 9(Day 1 of Cycle 9 (Each cycle was 21 days.))
  • Maximum Plasma Concentration (Cmax) of Sotatercept at Cycle 9(Day 1 of each 21-day cycle: Cycles 1-9)
  • Minimum Plasma Concentration (Cmin) of Sotatercept at Cycle 9(Day 1 of each 21-day cycle: Cycles 1-9)
  • Average Concentration (Cavg) of Sotatercept at Cycle 9(Day 1 of each 21-day cycle: Cycles 1-9)
  • Apparent Volume of Distribution (Vz/F) of Sotatercept at Cycle 9(Day 1 of each 21-day cycle: Cycles 1-9)
  • Absorption Rate Constant (Ka) of Sotatercept at Cycle 9(Day 1 of each 21-day cycle: Cycles 1-9)
  • Area Under the Concentration-Time Curve From 0 to T (AUC0-T) of Sotatercept at Cycle 9(Day 1 of each 21-day cycle: Cycles 1-9)
  • Apparent Terminal Half-life (t1/2 ) of Sotatercept at Cycle 9(Day 1 of each 21-day cycle: Cycles 1-9)
  • Apparent Serum Clearance (CL) of Sotatercept at Cycle 9(Day 1 of each 21-day cycle: Cycles 1-9)

研究者

发起方
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
申办方类型
Industry
责任方
Sponsor

研究点 (8)

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