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

October 21, 2025 updated by: UniQure Biopharma B.V.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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 rules for dose translation from preclinical (animal) studies to humans. Subsequent dose cohort levels are decided based on the review of safety, tolerability, and PK/PD results by an Independent Data Monitoring Committee and in agreement with the Sponsor.

Participants will be monitored through study site visits, blood tests, imaging questionnaires, and other assessments as per the study protocols.

Study Type

Interventional

Enrollment (Estimated)

12

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • The Kirklin Clinic of University of Alabama Birmingham Hospital
        • Contact:
        • Principal Investigator:
          • Eric Wallace, MD
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University School of Medicine
        • Principal Investigator:
          • William Wilcox, MD
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Ann & Robert H. Lurie Children's Hospital of Chicago
        • Principal Investigator:
          • Carlos E Prada, MD
        • Contact:
        • Contact:
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • MHealth Fairview University of Minnesota Medical Center East Bank
        • Contact:
        • Contact:
        • Principal Investigator:
          • Chester B Whitley, MD
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • NYC Health + Hospitals/Metropolitan
        • Principal Investigator:
          • Maryam Banikazemi
        • Contact:
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Recruiting
        • UPMC Children's Hospital of Pittsburgh
        • Contact:
        • Principal Investigator:
          • Damara Ortiz, MD
    • Utah
      • Salt Lake City, Utah, United States, 84108
        • Recruiting
        • University of Utah, Clinical and Translational Sciences Institute
        • Contact:
        • Contact:
        • Principal Investigator:
          • Brian Shayota, MD, MPH
    • Virginia
      • Fairfax, Virginia, United States, 22030
        • Recruiting
        • Lysosomal & Rare Disorders Research and Treatment Center, Inc
        • Principal Investigator:
          • Ozlem Goker-Alpan
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Ranging Cohort 1
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.
Experimental: Dose Ranging Cohort 2
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.
Experimental: Dose Ranging Cohort 3
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Evaluate the safety and tolerability of different dose levels of intravenously-administered AMT-191 in Participants with FD
Time Frame: 60 Months
60 Months
Incidence of Treatment-Emergent Adverse Events (TEAE)
Time Frame: 60 Months
60 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Characterize the vector shedding of intravenously-administered AMT-191
Time Frame: 60 Months
Duration of vector deoxyribonucleic acid (DNA) shedding present in blood, saliva, feces, semen, and urine.
60 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UniQure Biopharma B.V.

Investigators

  • Study Director: Arian Pano, MD, MPH, Clinical Development and Progam Lead, uniQure Biopharma, B.V.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 5, 2024

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

April 30, 2031

Study Registration Dates

First Submitted

December 19, 2023

First Submitted That Met QC Criteria

February 20, 2024

First Posted (Actual)

February 21, 2024

Study Record Updates

Last Update Posted (Estimated)

October 23, 2025

Last Update Submitted That Met QC Criteria

October 21, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CT-AMT-191-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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