AMT-191 for Fabry Disease

Recruiting at 7 trial locations

Overseen By uniQure

Age: 18 - 65

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: UniQure Biopharma B.V.

Must be taking: Enzyme replacement therapy

Must not be taking: Chaperone therapy, Anticoagulants

Disqualifiers: Allergy to ERT, Proteinuria, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called AMT-191 for individuals with Fabry disease. The main goals are to assess the treatment's safety and its behavior in the body. Participants will receive varying doses to determine the optimal and safest amount. Suitable candidates have a confirmed diagnosis of classic Fabry disease, experience moderate to severe pain or digestive issues, and have not responded well to current enzyme replacement therapy. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must continue your enzyme replacement therapy (ERT) until you meet the criteria for withdrawal. If you are using chaperone therapy like migalastat, you cannot participate in the trial.

Is there any evidence suggesting that AMT-191 is likely to be safe for humans?

Studies have shown that AMT-191 is generally safe. In earlier research, a specific dose led to two serious side effects. However, most participants found the side effects manageable, meaning they weren't too severe. This suggests that AMT-191 could be a promising option for people with Fabry disease, although, like any new treatment, it may have some risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about AMT-191 for Fabry Disease because it introduces a novel approach to treatment through gene therapy. Unlike traditional treatments such as enzyme replacement therapies, which require regular infusions to manage symptoms, AMT-191 aims to provide a longer-lasting solution by addressing the underlying genetic cause of the disease. This gene therapy has the potential to reduce the frequency of treatments and improve quality of life by offering a more sustainable and effective way to manage Fabry Disease.

What evidence suggests that AMT-191 might be an effective treatment for Fabry disease?

Research has shown that AMT-191 might help treat Fabry disease. In one study, patients experienced a significant boost in α-Gal A enzyme activity, with levels increasing 27 to 208 times higher than normal. This enzyme is crucial because it breaks down fats that accumulate in the cells of people with Fabry disease. Early studies also suggest that AMT-191 can reduce harmful substances like lysoGb3 in the body. The treatment aims to encourage the liver to produce more of the enzyme missing in Fabry disease, which may help manage the condition. Participants in this trial will receive different doses of AMT-191 to evaluate its effectiveness and safety. ^{1 2 4 5 6}

Who Is on the Research Team?

Arian Pano, MD, MPH

Principal Investigator

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

Are You a Good Fit for This Trial?

This trial is for men aged 18-50 with classic Fabry Disease, showing minimal GLA enzyme activity or a specific genetic variant. Participants must have moderate to severe gastrointestinal symptoms and persistent neuropathic pain. They should have an eGFR indicating moderate kidney function and weigh ≤80 kg. Candidates must agree to vaccination requirements and use condoms for 18 months post-dosing.

Inclusion Criteria

I haven't had any vaccinations 6 weeks before or plan to have any within 6 weeks after getting AMT-191.

eGFR between 45 mL/min/1.73 m2 and 75 mL/min/1.73m2

Able and willing to provide informed consent

Exclusion Criteria

Hypersensitivity reaction to ERT or infusion reaction in the 12 months prior to consent with specific severity criteria

Proteinuria with urine creatinine ratio > 1 at Screening

Positive serology test at Screening for certain infections

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous dose of AMT-191 and continue enzyme replacement therapy until criteria for withdrawal are met

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, tolerability, and exploratory efficacy, including the incidence of treatment-emergent adverse events and vector DNA shedding

26 months

What Are the Treatments Tested in This Trial?

Interventions

• AMT-191

Trial Overview The study tests AMT-191's safety, how it affects the body (PK/PD), and potential benefits in treating Fabry Disease over two years. It involves two groups receiving different doses of AMT-191 intravenously while continuing their regular enzyme replacement therapy.

How Is the Trial Designed?

Group I: Dose Ranging Cohort 3 Experimental Treatment 1 Intervention

Group II: Dose Ranging Cohort 2 Experimental Treatment 1 Intervention

Group III: Dose Ranging Cohort 1 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

UniQure Biopharma B.V.

Lead Sponsor

Trials

12

Recruited

260+

Published Research Related to This Trial

A new prognostic severity score, called the Fabry International Prognostic Index (FIPI), was developed using data from 1483 patients with Anderson-Fabry disease, allowing for the differentiation of patient groups based on their risk of disease progression.

The FIPI can predict outcomes for cardiac, renal, and neurological complications, with significant differences in event-free survival of up to 10 years between different risk groups, making it a useful tool for patient management and treatment comparisons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fabry International Prognostic Index: a predictive severity score for Anderson-Fabry disease. Hughes, DA., Malmenäs, M., Deegan, PB., et al.[2012]

In a study of 53 adult patients with Anderson-Fabry disease, early initiation of enzyme replacement therapy (ERT) was associated with a slower decline in lung function, suggesting that starting treatment sooner may help preserve pulmonary health.

Plasma levels of Lyso-Gb3 may serve as a potential marker for predicting airflow limitations in patients, indicating its usefulness in monitoring disease progression and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary involvement in Fabry disease: effect of plasma globotriaosylsphingosine and time to initiation of enzyme replacement therapy. Franzen, D., Haile, SR., Kasper, DC., et al.[2022]

Fabry disease is caused by a deficiency of the enzyme alpha-galactosidase A, leading to the accumulation of harmful substances in various tissues, which results in multi-organ symptoms.

Current treatments include enzyme replacement therapy and oral pharmacological chaperones, while future strategies may involve innovative approaches like stem cell therapy and gene therapy to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Anderson-Fabry Disease. Simonetta, I., Tuttolomondo, A., Daidone, M., et al.[2021]

Anderson-Fabry disease (AFD) is a serious genetic disorder caused by a deficiency in the enzyme alpha-galactosidase A, leading to harmful accumulation of certain fats in the body, primarily affecting males but also impacting carrier females.

Recent advancements in treatment include the approval of two recombinant enzyme formulations in Europe, which offer a promising targeted therapy for AFD, moving beyond just symptomatic management to potentially improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the management of Anderson-Fabry disease: enzyme replacement therapy. Pastores, GM., Thadhani, R.[2019]

Fabry disease is an X-linked disorder caused by a deficiency in the enzyme a-galactosidase A, leading to harmful accumulation of globotriaosylceramide and affecting multiple organs.

Enzyme replacement therapy (ERT) has shown long-term efficacy in reducing disease burden in Fabry disease patients, but it also has limitations that need to be addressed as treatment options evolve.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anderson-Fabry disease: developments in diagnosis and treatment. Mehta, AB.[2019]

Citations

1. uniqure.gcs-web.com uniqure.gcs-web.com/news-releases/news-release-details/uniqure-announces-initial-amt-191-phase-iiia-data-showing

uniQure Announces Initial AMT-191 Phase I/IIa Data Showing ... ... ~ All patients in the first cohort achieved between 27- to 208-fold increases in α-Gal A activity relative to mean normal level ~.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06270316

Safety, PK/PD, and Exploratory Efficacy Study of AMT-191 ... 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 ...

3. uniqure.com uniqure.com/programs-pipeline/fabry-disease

Fabry Disease | Programs & Pipeline Pre-clinical studies have shown that AMT-191, driven by a proprietary liver-specific promoter, results in a high degree of (lyso)Gb3 lowering, cross-correction ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2329050124001918

Preclinical efficacy and safety of adeno-associated virus 5 ... AAV5-GLA was developed to be a potential one-time treatment for Fabry disease, which is a rare, inherited, multi-systemic, X-linked, lysosomal storage disorder.

5. cdn.craft.cloud cdn.craft.cloud/fe68e1a2-b284-4f69-ba29-921f065edf17/assets/uploads/ICIEM_Final_Sept-2025-AMT-191-Initial-Fabry-Data.pdf

AMT-191 investigational gene therapy in adult males with ... AMT-191 is an investigational agent that has not been approved by the U.S.. Food and Drug Administration or any other regulatory health ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06270316

Safety, PK/PD, and Exploratory Efficacy Study of AMT-191 ... 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 ...