A Fabry Disease Gene Therapy Study (MARVEL1)
Fabry Disease, Lysosomal Storage Diseases
About this trial
This is an interventional treatment trial for Fabry Disease focused on measuring Gene Therapy
Eligibility Criteria
Inclusion Criteria:
- Adult males, ≥ 18 years of age with classic Fabry disease.
- Confirmed diagnosis of classic Fabry Disease
- Decreased plasma alpha galactosidase (αGLA) activity at screening.
- One or more of the characteristic features of classic Fabry disease.
- Elevated plasma LysoGb3 levels at screening (Part 2 only)
- Estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73m2 at screening.
- <500 mg/g Urine Protein to Creatinine Ratio (UPCR) in a spot urine sample OR < 1g/24 hours of urinary protein (24hour urine analysis), at
- Able to give full informed consent and able to comply with all requirements of the trial including long term follow-up.
- Willingness to practice barrier contraception whilst vector shedding via semen is present.
- Lack of AAV neutralising antibodies.
- For inclusion in Part 1, subjects must have received a licensed ERT or PCT for at least 12 months prior to dosing. For inclusion in Part 2, subjects must never have been previously dosed with ERT or PCT.
Exclusion Criteria:
- Non-classical Fabry disease.
- Presence of antibodies to αGLA, Replagal, or Fabrazyme.
- Subjects with chronic kidney disease.
- Subjects with severe myocardial fibrosis.
- Use of investigational therapy for Fabry disease within 60 days before enrolment. In addition, participation in any other clinical trial of an investigational medicinal product (IMP), and/or receiving any other IMP during the course of the study
- Evidence of liver dysfunction.
- Platelet count < 100 xE9L.
- Subjects receiving warfarin or other anticoagulants or subjects with a clinically significant bleeding disorder.
9 - 12. Either history of, or a positive serology test at screening for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCAb) and human immunodeficiency virus (HIV) or a negative test at screening for anti-varicella zoster virus (VZV) IgG.
13. Subjects with a history of or a positive screening test for tuberculosis. 14. Subjects who have received a live attenuated vaccination within 12 weeks prior to screening or intend to receive such a vaccine within the course of the study.
15. Uncontrolled glaucoma, diabetes mellitus, or hypertension. 16. Malignancy requiring treatment. 17. Subjects with uncontrolled cardiac failure, unstable angina, or myocardial infarction in the past 6 months.
18. Acute cardiac failure, unstable angina or myocardial infarction in the past 6 months.
19. Prior treatment with any gene transfer medicinal product. 20. Known or suspected intolerance to Replagal, Fabrazyme or any NIMPs used in the study.
21. Subjects with contraindications to MRI. 22. Subjects who have had a renal transplant. 23. Cytomegalovirus immunoglobulin positive subjects who are CMV PCR positive at screening.
24-25.History of physical or psychiatric illness that could affect the subject's ability to participate or a history of substance abuse including alcohol abuse.
Sites / Locations
- Kaiser Permanente
- Columbia University
- UPMC Children's Hospital of Pittsburgh
- Lysosomal and Rare Disorders Research and Treatment Center
- Medical University of Vienna
- Metabolics and Genetics in Calgary (MAGIC Clinic)
- Charité - Universitätsmedizin Berlin
- UKEA University Hospital Hamburg
- University of Würzburg
- Universita Federico II di Napoli
- Haukeland University Hospital
- Royal Free Hospital
- Salford Royal NHS Foundation Trust
Arms of the Study
Arm 1
Experimental
FLT190
FLT190 is a recombinant adeno- associated viral (AAV) vector. Administered by a single intravenous infusion.