EUCTR2018-002097-51-AT进行中（未招募）1 期
A Phase 1/2, Baseline-controlled, Non-randomized, Open-label, Single-ascending Dose Study of a Novel Adeno-associated Viral Vector (FLT190) in Patients With Fabry disease - MARVEL1
Freeline Therapeutics Ltd0 个研究点目标入组 15 人开始时间: 2021年3月24日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 15
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- Male
入选标准
- •1. Adult males, =18 years of age with classic Fabry disease.
- •2. Confirmed diagnosis of classic Fabry disease (including historical documentation of a classic pathological GLA mutation).
- •3. Plasma aGLA activity at screening (measured by central laboratory activity assay at trough) less than 5% of normal according to the central laboratory reference range.
- •4. One or more of the characteristic features of classic Fabry disease: neuropathic pain, corneal verticillata, clustered skin angiokeratoma.
- •5. Estimated glomerular filtration rate (eGFR) =60mL/min/1.73m2 at screening, per serum, using CKD Epidemiology Collaboration (CKD-EPI) equation.
- •6. <500mg/g UPCR in a spot urine sample OR if =500 mg/g, <1 g/24 hours of urinary protein (24 hour urine analysis), at screening.
- •7. Provision of full informed consent and able to comply with all requirements of the study and willingness to consider participating in the including 5-year long term follow-up.
- •8. Willing to practice barrier contraception (as specified in the protocol).
- •9. Lack of neutralizing anti-AAVS3 antibodies using an in vitro transduction inhibition assay within 6 weeks prior to vector administration.
- •10. For inclusion in Part 1, subjects must have received either a licensed ERT or PCT for at least 12 months prior to FLT190 dosing, at a stable dose (subjects receiving both ERT and PCT will be ineligible). For inclusion in Part 2, subjects must have never previously received treatment with either ERT or PCT (licensed or investigational).
- •11. Willingness to avoid strenuous exercise during first 3 months after FLT190 dosing.
- •Are the trial subjects under 18? no
- •Number of subjects for this age range:
- •F.1.2 Adults (18-64 years) yes
- •F.1.2.1 Number of subjects for this age range 13
- •F.1.3 Elderly (>=65 years) yes
- •F.1.3.1 Number of subjects for this age range 2
排除标准
- •1. Presence of GLA mutations leading to non-classical Fabry disease manifestation and any mutations that have not yet been classified. NOTE: Refer to Fabry Disease mutation database to determine classic and non-classical mutations. E.g., International Fabry Disease Genotype-Phenotype Database. If there is any uncertainty around the mutation classification discuss with Medical Monitor. (http://www.dbfgp.org/dbFgp/fabry/Mutation.html).
- •2. Prior hypersensitivity or intolerance to ERT.
- •3. Prior lack of response to ERT.
- •4. Subjects with a history of chronic kidney disease, stages 3-5 Kidney Disease: Improving Global Outcomes (KDIGO 2012 classification), documented in medical records for a minimum of 3 months.
- •5. Subjects with myocardial fibrosis (=3 segments) identified by MRI at screening.
- •6. Use of investigational therapy for Fabry disease within 60 days before enrolment. In addition, participation in any other clinical study of an investigational medicinal product (IMP), and/or receiving any other IMP during the study
- •7. Persistently elevated ALT or aspartate aminotransferase (AST); or bilirubin >1.5 x upper limit of normal, during screening).
- •8. Platelet count < 100 x 10^9/L.
- •9. Subjects receiving warfarin or other anticoagulants interfering with the ability to perform renal or skin biopsies, or subjects with a clinically significant bleeding disorder.
- •10. A history of hepatitis B infection, or a positive serology test at screening for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb), or negative for hepatitis B surface antibody (HBsAb).
- •11. A positive serology test at screening for hepatitis C antibody (HCAb) with a positive HCV-RNA load assay, or currently undergoing anti-viral therapy for hepatitis C
- •12. A negative test at screening for anti-varicella zoster virus (VZV) IgG
- •13. Either history of HIV infection, or a positive serology test at screening for human immunodeficiency virus (HIV)
- •14. A history of tuberculosis, or a positive screening test for tuberculosis at screening. The screening test may be repeated once following an indeterminate result.
- •15. Subjects who have received live attenuated vaccination within 12 weeks prior to screening, or intend to receive such vaccination during the course of the study
- •16. Uncontrolled glaucoma, diabetes mellitus, or hypertension.
- •17. History of any malignancy requiring treatment.
- •18. History or detection of significant arrhythmia on screening assessments with ECG/24-hour Holter monitoring. A significant arrhythmia includes those deemed clinically significant by the investigator e.g. advanced heart block (2nd or 3rd degree), supraventricular or ventricular arrhythmias.
- •19. Subjects with uncontrolled cardiac failure, unstable angina, or myocardial infarction or other cardiac presentations deemed significant by the investigator in the past 6 months.
- •20. History of acute myocarditis or presence of acute myocarditis during screening.
- •21. Prior treatment with any gene therapy medicinal product.
- •22. Known or suspected intolerance, hypersensitivity or contraindication to gadolinium, tacrolimus and other macrolides, steroids, local anesthetics used for skin or renal biopsies,the IMP and non-investigational medicinal products (NIMPs) or their excipients.
- •23. Subjects who are assessed as having any contraindications to MRI. Including subjects with ferromagnetic metallic implants, including pacing and defibrillator devices, nerve stimulators and cochlear implants.
研究者
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