AMT-191 for Fabry Disease

Recruiting at4 trial locations

Age: 18 - 65

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

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

Trial Summary

What is the purpose of this trial?

This is an open-label, multi-center study to evaluate safety, tolerability, and exploratory efficacy of a single dose of intravenously-administered AMT-191. The plan is to investigate 2 sequential dose cohorts with 3-6 Participants per cohort. Participants will continue receiving regularly scheduled enzyme replacement therapy (ERT) until they meet the criteria for withdrawal.

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.

How does the drug AMT-191 differ from other treatments for Fabry disease?

AMT-191 is unique because it may involve a novel approach compared to traditional enzyme replacement therapy (ERT) and oral pharmacological chaperones, which are the current standard treatments for Fabry disease. While ERT focuses on replacing the deficient enzyme, AMT-191 could potentially offer a different mechanism or administration method, although specific details about its uniqueness are not provided in the available research. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• AMT-191 (Enzyme Replacement Therapy)

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.

Participant Groups

Group I: Expansion Dose Cohorts Experimental Treatment 1 Intervention

Dose level 1: 6.0 x 10e13 gc/kg - Additional 3 if needed to assess dose-limiting toxicity Dose level 2: 3.0 x 10e14 gc/kg - Additional 3 if needed to assess dose-limiting toxicity

Group II: Dose Escalating Low and High Cohorts Experimental Treatment 1 Intervention

Dose level 1: 6.0 x 10e13 gc/kg - 3 Participants (plus additional 3 if needed to assess dose-limiting toxicity) Dose level 2: 3.0 x 10e14 gc/kg - 3 Participants (plus additional 3 if needed to assess dose-limiting toxicity)

Who Is Running the Clinical Trial?

UniQure Biopharma B.V.

Lead Sponsor

Trials

12

Recruited

260+

Findings from Research

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pulmonary involvement in Fabry disease: effect of plasma globotriaosylsphingosine and time to initiation of enzyme replacement therapy. [2022]

2. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Treatment of Anderson-Fabry Disease. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Fabry International Prognostic Index: a predictive severity score for Anderson-Fabry disease. [2012]

4. England pubmed.ncbi.nlm.nih.gov

Advances in the management of Anderson-Fabry disease: enzyme replacement therapy. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

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