A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial of GKT137831 in Patients With Idiopathic Pulmonary Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 8
- 主要终点
- Surrogate biomarker of oxidative stress by mass spectroscopy
研究概览
简要总结
A placebo-controlled, multicenter, randomized trial to test GKT137831 in ambulatory patients with idiopathic pulmonary fibrosis. This drug is an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) isoforms. The investigators hypothesize the drug will decrease pulmonary injury due to reactive oxygen species (ROS) generated by NOX enzymes, which are believed to play an important role in the development of IPF. Treatment with GKT137831 could result in significant benefit for a lung disease that has, until now, been almost invariably inexorable.
This clinical trial represents the bedside application of a series of NOX translational and basic studies and discoveries, over several years, from the laboratory of Dr. Victor Thannickal.
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
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 40-85 years old.
- •A diagnosis of IPF that fulfills current American Thoracic Society (ATS) Consensus Criteria.
- •IPF duration <5 years, based on the date of definitive diagnosis.
- •Ability and willingness to give informed consent and adhere to study requirements.
- •Ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) >70% of predicted values
排除标准
- •Diagnosis of major comorbidities expected to interfere with study participation
- •History of malignancy, excluding basal or squamous cell skin cancer and low-risk prostate cancer, the latter defined as stage T1 or T2a, with prostate specific antigen <10 ng/dl. NOX inhibition is not known to promote cancer, and these criteria are within current guidelines.
- •The occurrence of any acute infection requiring systemic antibiotic therapy within 2 weeks prior to Screening (Visit 1).
- •Treatment for >14 days within the preceding month with >20 mg. prednisone (or equivalent) or any treatment during the last month with a cellular immunosuppressant (e.g., cyclophosphamide, methotrexate, calcineurin inhibitors, etc.), given increased risks of opportunistic infections.
- •Treatment with any investigational agent within 4 weeks of Screening (Visit 1) or 5 half-lives of the investigational medicinal product (whichever is longer).
- •Fertile women who do not agree to contraception or abstinence, or who are breast feeding. IPF is a disease of older adults, and male predominant, so this will not be a frequent consideration.
- •Subjects with known hypersensitivity to GKT137831 or its excipients (e.g. capsule "bulking" agents).
- •A history of bone marrow disorder including aplastic anemia, or marked anemia defined as hemoglobin < 10.0 g/dL (or 6.2 mmol/L).
- •Severe cardiovascular disease, defined as any of the following within the preceding 12 weeks: acute myocardial infarction or unstable angina, a coronary revascularization procedure, congestive heart failure (NYHA Class III or IV), or stroke, including a transient ischemic attack.
- •Evidence of cardiac conducting abnormalities, defined as second or third degree atrial-ventricular (AV) block not successfully treated with a pacemaker, or a personal or family history of long QT syndrome (QTc interval >450 msec for males or 470 msec for females).
- •End-stage renal disease requiring dialysis.
- •Undergoing transplantation evaluation, or listed with the United Network for Organ Sharing (UNOS) as a lung transplantation candidate at the time of enrollment in this trial.
- •Liver function tests (transaminases, alkaline phosphatase, direct and total bilirubin) >3x upper limit of normal values
研究组 & 干预措施
Placebo Oral Tablet
Identically-appearing placebo oral tablets will be administered orally, twice daily, for a total of 24 weeks.
干预措施: Placebo Oral Tablet (Other)
GKT137831
GKT137831 will be administered orally, at a dose of 400 mg twice daily, for a total of 24 weeks.
干预措施: GKT137831 (Drug)
结局指标
主要结局
Surrogate biomarker of oxidative stress by mass spectroscopy
时间窗: From baseline thru week 24
Changes in concentrations of circulating o,o'-dityrosine, as determined by mass spectroscopy in plasma, in terms of absolute concentrations and percentages of baseline, will be compared within and between treatment arm participants.
次要结局
- Pulmonary function by spirometry(Baseline to week 24)
- Collagen degradation product by enzyme linked immunoabsorbant assay(Baseline to week 24)
- Evaluation of safety by adverse events(Baseline to week 24)
- Ambulatory ability by measuring walk distance in six minutes(Baseline to week 24)
研究者
Steven R. Duncan, MD
PI
University of Alabama at Birmingham