A Phase 1/2, Single Dose, Dose Ranging Study of Intravenous AAV5-GLA (AMT-191) in Adult Males With Classic Fabry Disease
UniQure Biopharma B.V.
Summary
The main goals of this clinical study are to characterize safety and PK/PD of AMT-191 i.e. if drug doses used in the study are safe and tolerable and to understand how it acts in the body of people with Fabry disease.
Description
In Fabry disease, the enzyme α-galactosidase A is deficient. AMT-191 is an investigational gene therapy that encodes a recombinant serotype 5 based adeno-associated viral vector (rAAV5). AMT-191 is designed to target the liver for production of the enzyme α-galactosidase A (αGAL). AMT-191 is delivered via a single (one-time) intravenous (IV) infusion. In this first-in-human study of AMT-191, two or more dose levels will be tested. All eligible participants will receive AMT-191 at one of the dose levels; there is no placebo in this study. The starting dose level is decided based on accepted r…
Eligibility
- Age range
- 18–50 years
- Sex
- Male
- Healthy volunteers
- No
Key Inclusion Criteria: * Male of age ≥ 18 years and ≤50 years * Confirmed clinical diagnosis of classic Fabry disease (FD) defined as: 1. Absent or minimal αGAL A enzyme activity \< 1% of mean normal measured in plasma regardless of variant status; OR 2. α-galactosidase A (GLA) pathogenic or likely pathogenic variant associated with classic FD phenotype identified on molecular genetic testing with plasma αGLA A enzyme activity below lower bound of the reference range (as measured at trough enzyme replacement therapy \[ERT\] levels). * eGFR ≥ 40 mL/min/1.73 m2 * Suboptimal response after…
Interventions
- DrugAMT-191
A recombinant serotype 5 based adeno-associated viral vector (AMT-191) for one-time intravenous (IV) administration will be investigated in this study. This recombinant AAV5-based vector contains a coding deoxyribonucleic acid (DNA) sequence for human α-galactosidase A. Delivery of AMT-191 to the systemic circulation is expected to result in a therapeutic effect by promoting the liver expression of the lysosomal enzyme GLA in plasma levels in patients with Fabry disease.
Locations (8)
- The Kirklin Clinic Of university of Alabama Birmingham HospitalBirmingham, Alabama
- Emory University School of MedicineAtlanta, Georgia
- Ann & Robert H. Lurie Children's Hospital of ChicagoChicago, Illinois
- MHealth Fairview University of Minnesota Medical Center East BankMinneapolis, Minnesota
- NYC Health + Hospitals/MetropolitanNew York, New York
- UPMC Children's Hospital of PittsburghPittsburgh, Pennsylvania