Fabry DiseasePhase 1/2NCT06270316
Safety, PK/PD, and Exploratory Efficacy Study of AMT-191 in Classic Fabry Disease
A Phase 1/2 study testing AMT-191 in people with Fabry Disease, run by UniQure Biopharma B.V. at 10 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men only
- Conditions the study is for
- Fabry Disease
- What is being tested?
- AMT-191
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 10 sitesUnited States
- Study dates
- 5 Jun 2024to 30 Nov 2031
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male of age ≥ 18 years and ≤65 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
- Participant agrees to use a condom during sexual intercourse with any female partner who could become pregnant
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- 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) and ≥ 45 kg
- Able and willing to provide informed consent
- Agrees to have no vaccinations within 6 weeks prior to and 6 weeks after dosing with AMT-191 unless allowed by stud protocol
Who cannot join
- 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
- Any anticipated participation in interventional studies for the treatment of FD
- Current use of chaperone therapy such as migalastat (Galafold®)
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- 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
- Moderately severe to severe cardiovascular disease, history of stroke or transient ischemic attacks within 12 months prior to Screening, history of ventricular tachycardia, history of or detection of other significant arrhythmia during Screening; significant thromboembolic disease history; or history of thrombotic risk resulting in current use of anticoagulant/antiplatelet agents.
- 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 12 months prior to Screening
- Screening laboratory values for renal and liver function that meet or exceed any of the following:
- Alanine transaminase (ALT) > 1.5 x upper limit of normal for the testing laboratory (ULN)
- Aspartate aminotransferase (AST) > 1.5 x ULN
- Total Bilirubin > ULN (except if this is caused by Gilbert disease)
- Alkaline phosphatase (ALP) > ULN
- Creatinine > 2 x ULN
- Direct bilirubin > ULN
- Albumin < 30 g/L
- Gamma-glutamyl transferase (GGT) > ULN
- Alpha-fetoprotein > 20 ng/mL unless cause is known and does not meet any other exclusion criteria
- Screening laboratory values for hematologic and coagulation function that meet any of the following:
- Hemoglobin < lower limit of normal (LLN) (as per reference laboratory ranges)
- Platelet count < 150 x1000/μl
- International normalized ratio (INR) >1.1
- 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
- Pre-existing ocular disease and/or intraocular pressure >21 mmHg at Screening unless referred for formal ophthalmology review and cleared b ophthalmologist to commence prednisone
- To be (re)-assessed on Day 0 prior to planned infusion:
- Active systemic bacterial, viral, or fungal infection
- ALT or AST ≥ 1.5 x ULN
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
United States10 sites, 10 recruiting
- Recruiting
Emory University School of Medicine
Atlanta, Georgia, 30322
Dawn Laney, 404-778-8518, dawn.laney@emory.edu
William Wilcox, MD
- Recruiting
The Kirklin Clinic Of University of Alabama Birmingham Hospital
Birmingham, Alabama, 35233
Christina Desruisseau, BSN, 205-975-2935, csingleton@uabmc.edu
Eric Wallace, MD
- Recruiting
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Carolyn Rasmussen, MS Genetic Counseling, 312.227.6763, crasmussen@luriechildrens.org
Esperanza Mendoza, eemendoza@luriechildrens.org
- Recruiting
Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Laurie Bailey, Laurie.Bailey@cchmc.org
Robert J. Hopkin, MD
- Recruiting
Lysosomal & Rare Disorders Research and Treatment Center, Inc
Fairfax, Virginia, 22030
Lauren Noll, (571) 732-4655, LNoll@ldrtc.org
BreAnna Davis, BDavis@ldrtc.org
- Recruiting
University of California Los Angeles (UCLA)
Los Angeles, California, 90095
Kimberly L. Schweigman, KSchweigman@mednet.ucla.edu
Nicola Longo, MD
- Recruiting
MHealth Fairview University of Minnesota Medical Center East Bank
Minneapolis, Minnesota, 55455
Melissa Fetterley, BSN, 612-672-5151, Melissa.Fetterley@fairview.org
Brenda Diethelm-Okita, Masters, dieth001@umn.edu
- Recruiting
NYC Health + Hospitals/Metropolitan
New York, New York, 10029
Alla Pinkhasova, (917) 796-8272, pinkhasa4@nychhc.org
Maryam Banikazemi
- Recruiting
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Jennifer Baker, 412-692-6378, Jennifer.Baker@chp.edu
Damara Ortiz, MD
- Recruiting
University of Utah, Clinical and Translational Sciences Institute
Salt Lake City, Utah, 84108
Carrie Bailey, Bachelor of Science, 801-587-3605, carrie.bailey@hsc.utah.edu
Jenny Billy, jenny.billy@hsc.utah.edu
About this study
Official title: 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.
Read the 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, three 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.
- Conditions
- Fabry Disease
- Being tested
- AMT-191
- Keywords
- GLA, gene therapy, ERT, FD
- Medical subject headings
- Fabry Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMT-191Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Dose Ranging Cohort 1 | Experimental | Not described Receives: Drug: AMT-191 |
| Dose Ranging Cohort 2 | Experimental | Not described Receives: Drug: AMT-191 |
| Dose Ranging Cohort 3 | Experimental | Not described Receives: Drug: AMT-191 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the safety and tolerability of different dose levels of intravenously-administered AMT-191 in Participants with FD
Measured: 60 Months
Secondary 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.
Measured: 60 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2024
- Study start5 Jun 2024
- Primary completion1 Dec 2027 (estimated)
- Study completion30 Nov 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UniQure Biopharma B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Arian Pano, MD, MPH, Study director, Clinical Development and Program Lead, uniQure biopharma, B.V.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06270316
- Sponsor's protocol ID
- CT-AMT-191-01
- Status last verified
- Sep 2026
- First submitted
- 19 Dec 2023
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Single Dose, Dose Ranging Study of Intravenous AAV5-GLA (AMT-191) in Adult Males With Classic Fabry Disease
- ClinicalTrials.gov ID
- NCT06270316
- Acronym / sponsor ID
- CT-AMT-191-01
- Conditions
- Fabry Disease
- Keywords
- GLA, gene therapy, ERT, FD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- UniQure Biopharma B.V.Industry (pharma, biotech, devices)
- Study start
- 5 Jun 2024 (actual)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 30 Nov 2031 (estimated)
- First posted
- 21 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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, three 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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Ranging Cohort 1 | Experimental | Drug: AMT-191 |
| Dose Ranging Cohort 2 | Experimental | Drug: AMT-191 |
| Dose Ranging Cohort 3 | Experimental | Drug: AMT-191 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Male of age ≥ 18 years and ≤65 years
- Confirmed clinical diagnosis of classic Fabry disease (FD) defined as:
- eGFR ≥ 40 mL/min/1.73 m2
- Participant agrees to use a condom during sexual intercourse with any female partner who could become pregnant
- 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:
Key exclusion criteria (37 listed)
- 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
- Any anticipated participation in interventional studies for the treatment of FD
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMT-191A 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. | Drug | Dose Ranging Cohort 1, Dose Ranging Cohort 2, Dose Ranging Cohort 3 |
Primary outcome
Evaluate the safety and tolerability of different dose levels of intravenously-administered AMT-191 in Participants with FD
Time frame: 60 Months
1 secondary outcome
Characterize the vector shedding of intravenously-administered AMT-191
Time frame: 60 Months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Arian Pano, MD, MPH study director
Clinical Development and Program Lead, uniQure biopharma, B.V.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AMT-191 in people with Fabry Disease, run by UniQure Biopharma B.V. at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact uniQure (1-866-520-1257, medinfo@uniqure.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the safety and tolerability of different dose levels of intravenously-administered AMT-191 in Participants with FD (time frame: 60 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.