RECRUITING

Safety, PK/PD, and Exploratory Efficacy Study of AMT-191 in Classic Fabry Disease

Conditions

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2024-06-05

Study Completion:2027-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06270316

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 50 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT

Inclusion Criteria	Exclusion Criteria
* Male of age ≥ 18 years and ≤50 years * 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)	* 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. * 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

Inclusion Criteria

Exclusion Criteria

* Male of age ≥ 18 years and ≤50 years
* 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)

* 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.
* 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

Contacts and Locations

Study Contact

uniQure

CONTACT

1-866-520-1257

medinfo@uniqure.com

Christy Quintana

CONTACT

734-680-7773

medinfo@uniqure.com

Principal Investigator

Arian Pano, MD, MPH

STUDY_DIRECTOR

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

Study Locations (Sites)

The Kirklin Clinic Of university of Alabama Birmingham Hospital

Birmingham, Alabama, 35233

United States

Emory University School of Medicine

Atlanta, Georgia, 30322

United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611

United States

MHealth Fairview University of Minnesota Medical Center East Bank

Minneapolis, Minnesota, 55455

United States

NYC Health + Hospitals/Metropolitan

New York, New York, 10029

United States

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224

United States

University of Utah, Clinical and Translational Sciences Institute

Salt Lake City, Utah, 84108

United States

Lysosomal & Rare Disorders Research and Treatment Center, Inc

Fairfax, Virginia, 22030

United States

Collaborators and Investigators

Sponsor: UniQure Biopharma B.V.

Arian Pano, MD, MPH, STUDY_DIRECTOR, Clinical Development and Progam Lead, uniQure Biopharma, B.V.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-06-05

Study Completion Date2027-12-01

Study Record Updates

Study Start Date2024-06-05

Study Completion Date2027-12-01

Terms related to this study

Keywords Provided by Researchers

GLA
gene therapy
ERT
FD

Additional Relevant MeSH Terms

Fabry Disease