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

UniQure Biopharma B.V.8 sites in 1 country12 target enrollmentJune 5, 2024

ConditionsFabry Disease

InterventionsAMT-191

DrugsAMT-191

Overview

Phase: Phase 1
Intervention: AMT-191
Conditions: Fabry Disease
Sponsor: UniQure Biopharma B.V.
Enrollment: 12
Locations: 8
Primary Endpoint: Evaluate the safety and tolerability of different dose levels of intravenously-administered AMT-191 in Participants with FD
Status: Recruiting
Last Updated: 6 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

Brief 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.

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.

Registry

clinicaltrials.gov

Start Date

June 5, 2024

End Date

April 30, 2031

Last Updated

6 months ago

Study Type

Interventional

Study Design

Sequential

Sex

Male

Investigators

Sponsor

UniQure Biopharma B.V.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male of age ≥ 18 years and ≤50 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
•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

•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.