Safety, PK/PD, and Exploratory Efficacy Study of AMT-191 in Classic Fabry Disease
NCT ID: NCT06270316
Last Updated: 2025-10-23
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE1/PHASE2
12 participants
INTERVENTIONAL
2024-06-05
2031-04-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Evaluation of the Long-term Safety, Pharmacodynamics, and Exploratory Efficacy of GZ/SAR402671 in Treatment-Naïve Adult Male Patients With Fabry Disease
NCT02489344
Safety, Pharmacodynamics, and Efficacy of Migalastat in Pediatric Subjects (Aged >12 Years) With Fabry Disease
NCT04049760
Study of the Safety and Biologic Activity of AL01211 in Treatment Naive Males With Classic Fabry Disease
NCT06114329
Open-Label Extension Study of the Long-Term Effects of Migalastat HCL in Patients With Fabry Disease
NCT02194985
A Long Term Follow-Up Study of Fabry Disease Subjects Treated With FLT190
NCT04455230
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Dose Ranging Cohort 1
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.
Dose Ranging Cohort 2
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.
Dose Ranging Cohort 3
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
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.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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)
Exclusion Criteria
* 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
18 Years
50 Years
MALE
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
UniQure Biopharma B.V.
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Arian Pano, MD, MPH
Role: STUDY_DIRECTOR
Clinical Development and Progam Lead, uniQure Biopharma, B.V.
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
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
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
CT-AMT-191-01
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.