Safety, PK/PD, and Exploratory Efficacy Study of AMT-191 in Classic Fabry Disease
ConditionFabry Disease
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexMale
Age18-65
SponsorUniQure Biopharma B.V.
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Male of age ≥ 18 years and ≤65 years
Absent or minimal αGAL A enzyme activity < 1% of mean normal measured in plasma regardless of variant status; OR
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
Disqualifiers
Any allergic hypersensitivity reaction to ERT or infusion reaction in the 12 months prior to consent that was of severity grade 3 or above based on Common Terminology Criteria for Adverse Events (CTCAE v5.0) and required emergency intervention for hypertension/hypotension to stabilize blood pressure or hypoxia OR any other life-threatening complication.
Proteinuria, with random urine protein/creatinine ratio (rUPCR) ≥1 mg/mg at Screening
Any previous treatment with investigational drug within 3 months prior to first Screening assessment
Any previous treatment with gene therapy
Trial design
Design model
Sequential
Treatments tested in this trial
AMT-191
DrugA 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.
Treatment groups
20 Participants
are divided into 3 treatment groupsGroup A: Dose Ranging Cohort 1Experimental treatment 1 intervention
Group B: Dose Ranging Cohort 2Experimental treatment 1 intervention
Group C: Dose Ranging Cohort 3Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Evaluate the safety and tolerability of different dose levels of intravenously-administered AMT-191 in Participants with FD
Time frame
60 MonthsSecondary outcomes
1
Characterize the vector shedding of intravenously-administered AMT-191
Duration of vector deoxyribonucleic acid (DNA) shedding present in blood, saliva, feces, semen, and urine.
Time frame
60 MonthsSponsors and contacts
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Source ClinicalTrials.gov