A Dose Escalation Study to Assess the Safety and Efficacy of Pulsed, Inhaled Nitric Oxide in Subjects With Pulmonary Hypertension Associated With Pulmonary Fibrosis or Sarcoidosis on Long Term Oxygen Therapy Followed by an Optional Open-Label Long Term Extension Safety Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Bellerophon
- 入组人数
- 17
- 试验地点
- 12
- 主要终点
- Measurement of PCWP
研究概览
简要总结
A phase 2b, open label study to assess the safety and efficacy of increasing doses of pulsed, inhaled nitric oxide (iNO) in subjects with pulmonary fibrosis and sarcoidosis on long term oxygen therapy followed by a long term extension study
详细描述
A phase 2b, open label study to assess the hemodynamic effects of increasing doses of pulsed, inhaled nitric oxide (iNO) in subjects with pulmonary hypertension associated with pulmonary fibrosis or sarcoidosis on long term oxygen therapy followed by an open label extension study
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent
- •A primary diagnosis of sarcoidosis as defined by the ATS/ERS/WASOG statement or pulmonary fibrosis associated with one of the following conditions:
- •2.1 Major IIPs (idiopathic interstitial pneumonias) diagnosed or suspected as one of the following:
- •Idiopathic pulmonary fibrosis
- •Idiopathic nonspecific interstitial pneumonia
- •Respiratory bronchiolitis-interstitial lung disease
- •Desquamative interstitial pneumonia
- •Cryptogenic organizing pneumonia
- •Acute interstitial pneumonia
- •Rare IIPs diagnosis by one of the following:
- •Idiopathic lymphoid interstitial pneumonia
- •Idiopathic pleuroparenchymal fibroelastosis
- •Unclassifiable idiopathic interstitial pneumonias
- •2.2 Chronic hypersensitivity pneumonitis
- •2.3 Occupational lung disease
- •2.4 Connective tissue disease with evidence of significant pulmonary fibrosis
- •Intermediate or high probability of PH by echocardiogram as assessed by local Radiologist/Investigator, or PH as determined by a right heart catheterization (RHC) within 5 years prior to Baseline with the following parameters:
- •Pulmonary vascular resistance (PVR) ˃3 Wood Units (WU) (320 dynes.sec.cm-5)
- •A left ventricular end diastolic pressure (LVEDP) or pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg
- •A mean pulmonary arterial pressure (mPAP) of ≥ 25 mmHg
- •6MWD ≥ 100 meters and ≤ 450 meters
- •WHO Functional Class II-IV
- •Forced Vital Capacity ≥ 40% predicted within last 6 weeks prior to screening
- •Females of childbearing potential must have a negative pre-treatment pregnancy test (urine).
- •Age between 18 and 85 years (inclusive)
- •Clinically stable for at least 4 weeks prior to Baseline in the opinion of the Investigator
- •If on therapy for their parenchymal lung disease and/or sarcoidosis, then the subject should be on a stable well-tolerated dose of the medication(s) for at least 4 weeks prior to enrollment.
排除标准
- •Use of any type of PAH specific therapies
- •Episodes of disease worsening within 3 months prior to Baseline
- •Pregnant or breastfeeding females at Screening
- •Administered L-arginine within 1 month prior to Screening
- •Any subject who has been enrolled in any previous clinical study with inhaled NO administered through pulsed delivery
- •On more than 6 L/min of oxygen at rest by nasal cannula for less than 4 weeks
- •Evidence of any connective tissue disease with FVC > 60% in the last 6 months prior to screening unless there is evidence of moderate to severe fibrosis on CT scan in the opinion of the local radiologist/Investigator
- •Evidence of clinically significant combined pulmonary fibrosis with emphysema (CPFE) if > 15% of lung fields by CT scan show evidence of emphysema in the opinion of the local radiologist/Investigator
- •For subjects with sarcoidosis, clinically significant evidence of pulmonary fibrosis on CT scan in the opinion of the local radiologist/Investigator and FVC ≥80% predicted
- •For subjects continuing on open label therapy, the concurrent use of the INOpulse device with a CPAP/BiPAP, or any other positive pressure device
- •Significant heart failure in the opinion of the Investigator
- •LVEF<40% or
- •PCWP on last RHC>15 mmHg (unless concurrent LVEDP <15 mmHg) or
- •Significant diastolic dysfunction on echocardiogram
结局指标
主要结局
Measurement of PCWP
时间窗: During a single right heart catheterization procedure
Pulmonary capillary wedge pressure (PCWP) will be measured at iNO 30, 45, 75 and 125 mcg/kg IBW/hr
Measurement of CO
时间窗: During a single right heart catheterization procedure
Cardiac output (CO) will be measured at iNO 30, 45, 75 and 125 mcg/kg IBW/hr
Measurement of PVR
时间窗: During a single right heart catheterization procedure
Pulmonary vascular resistance (PVR) will be measured at iNO 30, 45, 75 and 125 mcg/kg IBW/hr
Change in 6MWD from Baseline to 16 Weeks
时间窗: 16 weeks
Change in 6 minute walk distance
Measurement of mean PAP
时间窗: During a single right heart catheterization procedure
Mean pulmonary arterial pressure (mPAP) will be measured at iNO 30, 45, 75 and 125 mcg/kg IBW/hr
次要结局
- Incidence and Severity of Treatment Emergent Adverse Events(During a single right heart catheterization procedure)
- Distance Saturation Product (DSP)(16 weeks)
- Incidence of Adverse Events and Serious Averse Events(Through study completion; an average of 1 year)
- Pulmonary Rebound(During a single right heart catheterization procedure)
- Integral Distance Saturation Product (IDSP)(16 weeks)
- Dyspnea(16 weeks)
- Quality of Life Assessment(16 weeks)