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RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

Safety, PK/PD, and Exploratory Efficacy Study of AMT-191 in Classic Fabry Disease

A Phase 1/2, Single Dose, Dose Ranging Study of Intravenous AAV5-GLA (AMT-191) in Adult Males With Classic Fabry Disease

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

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.

Who May Be Eligible (Plain English)

Key Who May Qualify: - 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 at least 12 months of enzyme replacement therapy (ERT) treatment. Suboptimal response is defined as plasma lyso-Gb3 ≥ 2.3 nanograms per milliliter (ng/mL) at Screening and one or both of the following: - Persistent moderate or severe neuropathic pain (intermittent or continuous) over a period of at least 3 months prior to consent - Presence of gastrointestinal symptoms (abdominal cramping, constipation, or diarrhea), reported by the Participant as moderate or severe and that are either persistent or occurring two or more times over the 12 weeks prior to consent - Weight ≤ 120 kilograms (kg) Key Who Should NOT Join This Trial: - 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 - Current use of chaperone therapy such as migalastat (Galafold®) - Malignancy within 5 years of Screening, except for basal or squamous cell carcinoma of the skin ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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 at least 12 months of enzyme replacement therapy (ERT) treatment. Suboptimal response is defined as plasma lyso-Gb3 ≥ 2.3 nanograms per milliliter (ng/mL) at Screening and one or both of the following: * Persistent moderate or severe neuropathic pain (intermittent or continuous) over a period of at least 3 months prior to consent * Presence of gastrointestinal symptoms (abdominal cramping, constipation, or diarrhea), reported by the Participant as moderate or severe and that are either persistent or occurring two or more times over the 12 weeks prior to consent * Weight ≤ 120 kilograms (kg) Key Exclusion Criteria: * 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 * Current use of chaperone therapy such as migalastat (Galafold®) * Malignancy within 5 years of Screening, except for basal or squamous cell carcinoma of the skin * Presence of chronic, active, or latent infection with hepatitis B or C, human immunodeficiency virus (HIV), or tuberculosis (TB) as assessed at the screening visit * Active or ongoing infection or any other significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, cardiovascular, hematological, GI, endocrine (such as diabetes mellitus with poor glycemic control), pulmonary, neurological, cerebral, or psychiatric disease, alcoholism, drug dependency, or any other psychological disorder that could, in the opinion of the Investigator, risk the safety of the Participant, or interfere with adherence to the protocol procedures or interpretation of results * Evidence of any liver disease, including hepatitis, fibrosis, cirrhosis of the liver, neoplastic lesion, or any known medical condition that could impact the intended transduction of the vector and/or expression and activity of the protein * History of kidney transplantation or currently on hemodialysis or peritoneal dialysis * Uncontrolled hypertension, defined as systolic blood pressure \>140 millimeters of mercury (mmHg) (inclusive) and/or diastolic blood pressure outside the range of 60 to 85 mmHg (inclusive) at Screening, confirmed on at least 2 repeated measurements * Patients taking blood pressure medication to control blood pressure or proteinuria (eg, angiotensin-converting enzyme \[ACE\] inhibitors and angiotensin II receptor blockers \[ARBs\]) and have been titrated to a stable dose for at least 3 months prior to Screening are allowed in the study. * Glycated hemoglobin (HbA1c) at Screening ≥7% * Contraindication to systemic corticosteroid therapy or immunosuppressive therapy * Chronic steroid use, defined as ≥ 3 months of oral corticosteroid use within the 12 months prior to Screening * Screening laboratory values for renal and liver function that meet or exceed any of the following: 1. Alanine transaminase (ALT) \> 2 x upper limit of normal for the testing laboratory (ULN) 2. Aspartate aminotransferase (AST) \> 2 x ULN 3. Total Bilirubin \> 2 x ULN (except if this is caused by Gilbert disease) 4. Alkaline phosphatase (ALP) \> 2 x ULN 5. Creatinine \> 2 x ULN * Screening laboratory values for hematologic and coagulation function that meet any of the following: 1. Hemoglobin \< lower limit of normal (LLN) (as per reference laboratory ranges) 2. Platelet count \< 150 x1000/μl 3. International normalized ratio (INR) \>1.1 4. Soluble terminal complement complex (sC5b-9)\>ULN * Significant anatomical abnormalities on renal ultrasound such as the presence of only 1 kidney, significant differences in kidney sizes between the right and left kidneys \>1.5 centimeters (about 0.59 inch), or presence of kidney cysts

Treatments Being Tested

DRUG

AMT-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 Hospital
Birmingham, Alabama, United States
Emory University School of Medicine
Atlanta, Georgia, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
MHealth Fairview University of Minnesota Medical Center East Bank
Minneapolis, Minnesota, United States
NYC Health + Hospitals/Metropolitan
New York, New York, United States
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States
University of Utah, Clinical and Translational Sciences Institute
Salt Lake City, Utah, United States
Lysosomal & Rare Disorders Research and Treatment Center, Inc
Fairfax, Virginia, United States