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

NCT06270316 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CT-AMT-191-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Fabry Disease

Keywords

GLA; gene therapy; ERT; FD

Outcome Measures

Primary Outcomes (2)

• Evaluate the safety and tolerability of different dose levels of intravenously-administered AMT-191 in Participants with FD

  60 Months

• Incidence of Treatment-Emergent Adverse Events (TEAE)

  60 Months

Secondary Outcomes (1)

• Characterize the vector shedding of intravenously-administered AMT-191

  60 Months

Study Arms (3)

Dose Ranging Cohort 1

EXPERIMENTAL

Drug: AMT-191

Dose Ranging Cohort 2

EXPERIMENTAL

Drug: AMT-191

Dose Ranging Cohort 3

EXPERIMENTAL

Drug: AMT-191

Interventions

AMT-191 DRUG

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.

Dose Ranging Cohort 1; Dose Ranging Cohort 2; Dose Ranging Cohort 3

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Male of age ≥ 18 years and ≤ 50 years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male of age ≥ 18 years and ≤50 years
• Confirmed clinical diagnosis of classic Fabry disease (FD) defined as:
• 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
• 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)

You may not qualify if:

• 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:
• Alanine transaminase (ALT) \> 2 x upper limit of normal for the testing laboratory (ULN)

Sponsors & Collaborators

• UniQure Biopharma B.V.: lead

Study Sites (8)

The Kirklin Clinic Of university of Alabama Birmingham Hospital

Birmingham, Alabama, 35233, United States

RECRUITING

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

RECRUITING

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

RECRUITING

MHealth Fairview University of Minnesota Medical Center East Bank

Minneapolis, Minnesota, 55455, United States

RECRUITING

NYC Health + Hospitals/Metropolitan

New York, New York, 10029, United States

RECRUITING

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

University of Utah, Clinical and Translational Sciences Institute

Salt Lake City, Utah, 84108, United States

RECRUITING

Lysosomal & Rare Disorders Research and Treatment Center, Inc

Fairfax, Virginia, 22030, United States

RECRUITING

MeSH Terms

Conditions

Fabry Disease

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Arian Pano, MD, MPH

  Clinical Development and Progam Lead, uniQure Biopharma, B.V.

  STUDY DIRECTOR

Central Study Contacts

uniQure

CONTACT

1-866-520-1257; medinfo@uniqure.com

Christy Quintana

CONTACT

734-680-7773; medinfo@uniqure.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2023
• First Posted: February 21, 2024
• Study Start: June 5, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): April 30, 2031
• Last Updated: October 23, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)