NCT05128929已完成2 期
Investigation of H01 in Adults With Pulmonary Hypertension Including Interstitial Lung Disease (The SATURN Study).
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Calculated Pulmonary Vascular Resistance (PVR)
研究概览
简要总结
This study is a prospective, randomized, double-blind, study of H01 (Hymecromone) in adults with pulmonary hypertension (PH). The primary objective of this study is to evaluate the safety and tolerability of oral H01 and the potential benefit of oral H01 on clinical measures of PH disease severity over 24 weeks.
Study Hypothesis:
Oral H01, at doses of 1600 mg per day, will be a safe and well-tolerated agent in adults with pulmonary hypertension over 24 weeks
详细描述
The study's objectives are to evaluate:
- The changes in clinical and functional measures (pulmonary function test, pulmonary vascular resistance, mean pulmonary arterial pressure, and 6 Minute Walk Distance Test) in adults with PH treated with oral H01
- The safety and tolerability of the use of oral H01 for PH over 24 weeks using health criteria/evaluations (Common Terminology Criteria for Adverse Events (CTCAE), quality of life (QOL) score, EMPHASIS-10 score and St George Respiratory Questionnaire (SGRQ) score)
- To investigate the clinical efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) markers (serum HA concentration, inflammatory markers and cytokines, NT-proBNP, and H01 and metabolite serum concentrations) in this population following oral H01 use
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Classified as WHO functional class II/III/IV despite treatment with maximally tolerated doses of 2 or more treatment modalities (exp. PDE5 inhibitors, guanylate cyclase stimulators, endothelin receptor antagonists, and prostanoids)
- •Baseline 6MWT: greater than 100 meters and less than 550 meters
- •Established diagnosis of Group 3 pulmonary hypertension as a result of interstitial lung disease OR established diagnosis of Group 1 pulmonary hypertension as a result of connective tissue disease, idiopathic, hereditary, drugs, or toxins.
- •Right heart catheterization at randomization showing pre-capillary pulmonary hypertension (mPAP ≥ 25 mmHg and PVR > 400 dynes * sec * cm^ -5) and:
- •PCWP ≤20 mmHg for Group 3 PH patients and Group 1 PAH patients
- •Participants on chronic medication for PAH, PH, or underlying lung disease must be on a stable and optimized dose for at least 90 days prior to the first dose of the study drug.
- •Female participants who are heterosexually active must use an acceptable method of contraception: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, IUD, or Hormone-based contraceptive
- •Be able to provide written informed consent and comply with study requirements
- •Be able to read, speak and understand English
排除标准
- •Participants with a diagnosis of PAH or PH for reasons due to any of the following:
- •Group 2, 4, or 5
- •Group 1 due to HIV, veno-occlusive disease, porto-pulmonary hypertension, congenital heart disease
- •Group 3 due to severe chronic obstructive pulmonary disease (COPD) or obstructive sleep apnea (OSA)
- •Note: participants with overlapping syndromes will be evaluated on a case-by-case basis by the recruiting physician*
- •Total Lung Capacity (TLC) less than 60% predicted
- •FEV1/FVC less than 50% predicted or FEV1 less than 55% predicted
- •Inability to safely attempt completion of the 6MWD test
- •Use of experimental PAH treatments within the past 3 months
- •Current systemic treatment with hymecromone
- •Left sided heart disease as defined by either a PCWP greater than 20 mmHg and/or left ventricular ejection fraction less than 40%
- •Note: participants with abnormal left ventricular function attributable entirely to impaired left ventricular filling due to the effects of right ventricular overload (ie right ventricular hypertrophy and/or dilatation) are not excluded
- •Participants must not have 3 or more of the following left ventricular disease / dysfunction risk factors:
- •Body mass index (BMI) greater than 30kg/m2
- •History of essential hypertension requiring medication
- •Diabetes mellitus
- •Historical evidence of significant coronary disease established by any of the following:
- •History of myocardial infarction
- •History of percutaneous coronary intervention or coronary artery bypass graft
- •Angiographic evidence of greater than 50% stenosis in at least one coronary artery
- •Positive stress test with imaging
- •Stable angina
- •Significant valvular heart disease as determined by more than moderate findings on echocardiogram or history of valve replacement
- •Pregnant or actively breastfeeding
- •Female participants with childbearing potential not willing to use a form of birth control (including abstinence) during the study
- •Inability to undergo right heart catheterization
- •Acute pulmonary embolism within 90 days of randomization
- •Exacerbation of underlying lung disease or active pulmonary or upper respiratory infection within 30 days of randomizations
- •Use of any inhaled tobacco products or significant history of drug abuse within 3 months prior to randomization
- •Subject is receiving greater than 10L/min of oxygen supplementation by any mode of delivery at rest at baseline
- •Body mass index greater than 40kg/m2
- •Participants with history of dysphagia, achalasia, or difficulty swallowing capsules, tablets or pills
- •Participants with liver failure or AST or ALT greater than 2 times the upper limit of normal
- •Participants with total bilirubin levels greater than 2 times the upper limit of normal
- •Participants with CrCl less than 45
- •Use of any investigational drug/device, or participation in any investigational study with therapeutic intent within 30 days prior to randomization
- •Known allergy to hymecromone or any component thereof
- •Known allergy to any component of placebo (including wheat allergy, celiac disease, rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption)
- •Physician concern that participant may not adhere to the study protocol
- •Significant psychiatric, addictive, or other disorder that compromises the subject's ability to provide informed consent
研究组 & 干预措施
Experimental Treatment Oral Hymecromone (H01)
Experimental
Treatment will be initiated. Participants will be administered 800 mg of oral H01 two times a day (total dose: 1600 mg/day). Participants will continue to be on treatment for 24 weeks and will be monitored with assessments.
干预措施: Hymecromone (H01) (Drug)
Placebo
Placebo Comparator
Participants randomized to placebo will receive oral tablet placebo (inactive ingredients) two times a day. Participants will continue to be on placebo for 24 weeks and will be monitored with assessments.
干预措施: Placebo (Drug)
结局指标
主要结局
Calculated Pulmonary Vascular Resistance (PVR)
时间窗: Baseline to end of treatment (Week 24; +/- 7 days)
Calculated pulmonary vascular resistance (PVR) measured by right heart catheterization (RHC). A normal PVR ranges between 0.25 and 1.6 wood units (WU). Pre-capillary pulmonary hypertension is characterized by a PVR greater than 3 WU. Greater PVR is indicative of increased disease severity. Either Fick or Thermodilution method can be utilized to measure cardiac output (CO) and calculate PVR. Fick method utilizes estimated oxygen consumption to measure CO and calculate PVR, while the thermodilution method utilizes temperature change to measure CO and calculate PVR. All measurements to calculate PVR were obtained at end-expiration (measuring the pressures at functional residual capacity of the lungs).
次要结局
- Number of Participants With Adverse Events by Severity Using the NIH Common Terminology Criteria for Adverse Events (CTCAE) as a Measure of Safety and Tolerability of H01 in Adults With Pulmonary Hypertension(Baseline to end of treatment (Week 24; +/- 7 days))
- Mean Pulmonary Arterial Pressure (mPAP)(Baseline and end of treatment (Week 24; +/- 7 days))
- 6 Minute Walk Distance Test (6 MWDT)(Screening (up to 30 days prior to baseline) and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days).)
- EMPHASIS-10 Scale Score(Baseline and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days))
- St George Respiratory Questionnaire (SGRQ) Scale Score(Baseline and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days))
- Serum Hyaluronan (HA) Concentration(Baseline and end of treatment (Week 24; +/- 7 days))
- N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)(Baseline and weeks 4 (+/- 3 days), 12 (+/- 3 days), and 24 (+/- 7 days))
研究者
Roham T. Zamanian
Associate Professor of Medicine
Stanford University
研究点 (1)
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