An Open Label Study to Evaluate the Safety of Dasatinib in the Treatment of Scleroderma Pulmonary Interstitial Fibrosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 47
- 试验地点
- 13
- 主要终点
- Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
研究概览
简要总结
The purpose of this study was to evaluate the safety of Dasatininb in the treatment of scleroderma pulmonary interstitial fibrosis.
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
- •Target Population
- •meet American College of Rheumatology (ACR) criteria for scleroderma
- •have clinical evidence of active skin disease with a skin score of ≥15
- •have had the onset of their first non-Raynaud phenomenon feature of SSc no more than 3 years prior to screening
- •have evidence of fibrosing alveolitis (active pulmonary fibrosis) manifested by a forced vital capacity (FVC) between 45% and 80% of predicted normal and/or diffusing capacity (DLCO) between 30% and 70% of predicted normal values
- •have an abnormal high resolution Computed tomography (CT) scan of the chest/lungs demonstrating typical ground glass changes of alveolitis with background fibrosis
- •have adequate renal function- no evidence of renal crisis in the 2 months prior to enrollment and serum creatinine < 3 mg/dL
- •for both sexes, must use an acceptable form of birth control
排除标准
- •Clinically significant pleural or pericardial effusion in the previous 12 months: Grade 3 or
- •Patients with recent Grade I or II effusions or peripheral edema will be permitted to enter the study
- •Clinically significant cardiac disease (New York Heart Association Class III or IV) including preexisting arrhythmia, (such as ventricular tachycardia, ventricular fibrillation, or "Torsade de Pointes"), myocardial infarction, uncontrolled angina within 6 months, congestive heart failure, cardiomyopathy, or pericardial disease
- •Clinically-significant coagulation or platelet function disorder (eg, known von Willebrand's disease)
- •Abnormal QTcF interval prolonged (> 450 msec) after electrolytes have been corrected on baseline electrocardiogram
- •Laboratory Test Findings
- •Hgb < 10 g/dL; platelet count < 100,000/dL; WBC < 3,000/dL; PMN < 1,000/dL; OR lymphocytes < 350/dL
- •The presence of any of the following laboratory findings at screening: positive for antibodies to hepatitis C virus; positive for antibodies to hepatitis B surface antigen (HBsAg); serum bilirubin 2 times normal, Alanine Aminotransferase (ALT), or Aspartate Aminotransferase (AST)> 2.5 times upper limit of normal
- •Prohibited Treatments and/or Therapies
- •use of other immunosuppressive therapies must be discontinued at enrollment, eg methotrexate, azathioprine, cyclophosphamide, mycophenolic acid, mycophenolate mofetil, cyclosporine
- •treatment with any other experimental or investigational drug(s) concurrently or less than 12 weeks prior to study enrollment
- •use of anti-fibrotic agents must be discontinued at enrollment, eg colchicine, D-penicillamine, minocycline or Type 1 oral collagen
研究组 & 干预措施
A1
干预措施: dasatinib (Drug)
结局指标
主要结局
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
时间窗: From start of study drug therapy up to 30 days after the last dose. The duration of dasatinib dosing in this study was up to 2 years
GR0=normal,1=mild,2=moderate,3=severe,4=life-threatening. ALP(U/L) GR0:40-135,GR1:\>135-337; ALT(U/L) GR0:0-47,GR1:\>47-117; AST(U/L) GR0:0-37,GR1:\>37-93; High(↑) Calcium(mg/dL) GR0:8.4-10.2,GR1:\>10.2-11.5; Low(↓) Calcium(mg/dL) GR0:8.4-10.2,GR1:\<8.4-8.0,GR2:7.0-\<8.0; CK(U/L) GR0:24-195,GR1:\>195-488, GR2:\>488-975; Creatinine(mg/dL) GR0:0.6-1.4,GR1:\>1.4-2.1,GR2:\>2.1-4.2; ↑Potassium(mEq/L) GR0:3.6-5.2,GR1:\>5.2-5.5,GR2:\>5.5-6.0; ↑Sodium(mEq/L) GR0:134-146; ↓Sodium(mEq/L) GR0:134-146,GR1:\<134-130; Inorganic Phosphorus(mg/dL) GR0:2.4-4.9,GR2:≥2.0-\<2.5; Total Bilirubin(mg/dL) GR0:0-1.1,GR1:\>1.1-2.75.
Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), or Adverse Events (AEs)
时间窗: From start of study drug therapy up to 30 days after the last dose. The duration of dasatinib dosing in this study was up to 2 years
AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to any AEs were recorded.
Laboratory Test Results Summary of Toxicity: Hematology
时间窗: From start of study drug therapy up to 30 days after the last dose. The duration of dasatinib dosing in this study was up to 2 years
Toxicity was graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0. (Grade (GR)0=normal, GR1=mild, GR2=moderate, GR3=severe, GR4=life threatening). Granulocyte count (x 10\^9 /L), GR1: ≥1.0 - \<1.5, GR2: ≥0.5 - \<1.0; Hemoglobin (g/dL), GR0: 13-17, GR1: \<13 - 10.0 , GR2: 8.0 - \<10.0, GR3: 6.5 - \<8.0; Platelet count (x 10\^9 /L) GR0: 150-400, GR2: ≥50.0 - \<75.0; Leukocyte count (x 10\^9 /L ), GR0: 3.5-11.1, GR2: 2.0 - \<3.0.
Reasons for Discontinuation of Study Treatment
时间窗: From start of study drug therapy up to 30 days after the last dose. The duration of dasatinib dosing in this study was up to 2 years
Participants who discontinued the study due to any AEs were recorded. Significant drug-related discontinuations were those SAEs recorded on the SAE case report forms with relationship to study drug of related or missing and action taken regarding study drug of discontinued or missing.
次要结局
未报告次要终点