NCT02800070已完成1 期
Clinical Pilot Study of Autologous Stem Cell Transplantation of Cluster of Differentiation 34 Positive (CD34+) Cells Engineered to Express Alpha-Galactosidase A in Patients With Fabry Disease
适应症
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 3
- 主要终点
- Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
研究概览
简要总结
This is a first-in-human study for the treatment of Fabry disease. Eligible patients will have an autologous stem cell transplantation using CD34+ cells that are transduced with the lentivirus vector containing the human alpha-gal A gene. The researchers of this study would like to see if the re-introduction of transduced cells will help increase the levels of alpha-gal A enzyme levels and to determine the safety and toxicity of autologous stem cell transplantation using CD34+ cells transduced with lentivirus vector containing the alpha-gal A gene. This study's objective is to determine the safety and toxicity of lentivirus alpha-gal A transduced CD34+ cells in adult males with Fabry disease.
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 50 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male patients 18-50 years of age at the time of enrollment
- •Diagnosis of Fabry disease (FD) as defined by very low or absent α-gal A activity
- •Classic FD Type I phenotype with alpha-galactosidase A (GLA) genotyping
- •Patients on enzyme replacement therapy (ERT) prior to enrollment
- •Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1
- •Adequate organ function within 21 days prior to Pre-Treatment Phase:
- •Willing and capable of signing and giving written informed consent in accordance with Research Ethics Board (REB) requirements
- •Willing to comply with all procedures outlined in the study protocol, cooperative with the protocol schedule, able to return for safety evaluation, or otherwise likely to complete the study
- •Willing to abstain from sexual activity or willing to use condoms during sexual intercourse from day of Melphalan administration on day -1 of Phase 3 until after 12 months follow-up post-transplant.
- •Willing to not donate sperm after receiving Melphalan. Sperm banking will be recommended to any patient who would like to father children in the future.
排除标准
- •Males with variant Fabry Disease.
- •Female gender
- •Use of immunosuppressive agents or any anticoagulant
- •Ongoing ERT-related infusion associated reactions of moderate-to-severe intensity
- •Presence of anti-agalsidase immunoglobulin (Ig)G antibodies above a threshold (5-fold above normal;) or evidence of high titre neutralizing antibodies
- •Blood test positive for Hepatitis B virus (HBV), Hepatitis C virus (HCV), human immunodeficiency virus (HIV), human T-cell lymphotropic virus type 1 (HTLV-1), human T-cell lymphotropic virus type 1 (HTLV-2), or Venereal Disease Research Laboratory test (VDRL; Transmissible Disease (TD) testing will be done in Pre-Treatment Phase 2 - see section 5.1 for full panel of TD tests. Patients will only be excluded from the study if positive for the TD tests listed here in this exclusion).
- •Uncontrolled bacterial, viral, or fungal infections
- •Prior malignancies except resected basal cell carcinoma
- •Chronic Kidney Disease (CKD) stage >2
- •History of heart failure or left ventricle ejection fraction (LVEF) <45% or moderate to severe diastolic dysfunction by standard criteria
- •Arrhythmia: bundle branch block, heart block degree II or III, atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation, cardiac arrest, pacemaker, implantable cardiac defibrillator
- •Coronary artery disease with angina, prior myocardial infarction, percutaneous transluminal coronary angioplasty with or without stent, coronary artery bypass graft surgery, moderate to severe valvular heart disease, valve replacement surgery
- •Uncontrolled hypertension
- •Diabetes mellitus
- •Advanced liver disease, liver failure, cirrhosis
- •Immune deficiency state
- •Moderate-to-severe chronic obstructive pulmonary disease (COPD)
- •Any hematological condition with white blood cells (WBC) <3.0 x109/L, platelet count <100 x109/L, and/or hemoglobin <100 g/L
- •Prior bone marrow transplant (BMT) or organ transplant
- •Any condition that would preclude use of Melphalan
- •Use of a drug with cytotoxic or immunosuppressive effect within 60 days of trial entry
- •Uncontrolled psychiatric disorder
- •Active chronic infection
- •Prior tuberculosis
- •Any other serious concurrent disease
- •Cognitive impairment that would prevent informed consent
- •Use of an investigational drug within 30 days of stem cell transplant (SCT)
结局指标
主要结局
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
时间窗: 5 years
Safety measurement will be based on all clinical and laboratory assessment post-baseline. The assessment will be the frequency of clinically notable abnormal vital signs and laboratory values, and the frequency of treatment-related adverse events.
次要结局
- vector copy number per genome on the CD34+ cell population(5 years)
- lyso-Gb3 levels(5 years)
- lyso-Gb3 analogue (-28)(5 years)
- lyso-Gb3 analogue (-2)(5 years)
- Alpha-gal A enzyme activity levels(5 years)
- Gb3 levels(5 years)
- lyso-Gb3 analogue (+16)(5 years)
- lyso-Gb3 analogue (+34)(5 years)
- lyso-Gb3 analogue (+50)(5 years)
- transduction efficiency(5 years)
研究者
研究点 (3)
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