A Fabry Disease Gene Therapy Study

NCT04040049 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: FLT190-01
• Study Type: interventional
• Target: 3
• Locations: 7 countries
• Sites: 13

Brief Summary

This is a multinational, open-label study to assess the safety and efficacy of FLT190 in up to 15 adult male participants with classical Fabry disease.

Conditions

Fabry Disease; Lysosomal Storage Diseases

Keywords

Gene Therapy

Outcome Measures

Primary Outcomes (1)

• Frequency of treatment-emergent adverse events (AEs)

  To investigate the safety of systemic administration of FLT190.

  From screening to 12 weeks post infusion

Study Arms (1)

FLT190

EXPERIMENTAL

FLT190 is a recombinant adeno- associated viral (AAV) vector. Administered by a single intravenous infusion.

Genetic: FLT190

Interventions

FLT190 GENETIC

Gene Therapy product.

FLT190

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males, ≥ 18 years of age with classic Fabry disease.
• Confirmed diagnosis of classic Fabry Disease
• Decreased plasma alpha galactosidase (αGLA) activity at screening.
• One or more of the characteristic features of classic Fabry disease.
• Estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73m2 at screening.
• \<500 mg/g Urine Protein to Creatinine Ratio (UPCR) in a spot urine sample OR \< 1g/24 hours of urinary protein (24hour urine analysis), at
• Able to give full informed consent and able to comply with all requirements of the trial including the 5-year long term follow-up.
• Willingness to practice barrier contraception whilst vector shedding via semen is present.
• Lack of AAV neutralizing antibodies within 6 weeks prior to dosing.
• Willingness to avoid strenuous exercise during first 3 months after dosing.

You may not qualify if:

• Non-classical Fabry disease.
• Prior hypersensitivity or intolerance to ERT
• Prior lack of response to ERT.
• Subjects with a history of chronic kidney disease for a minimum of 3 months.
• Subjects with severe myocardial fibrosis.
• Use of investigational therapy for Fabry disease within 60 days before enrolment. In addition, participation in any other clinical trial of an investigational medicinal product (IMP), and/or receiving any other IMP during the course of the study
• Evidence of liver dysfunction as demonstrated by elevated blood levels during screening.
• Platelet count \< 100 xE9L.
• Subjects receiving warfarin or other anticoagulants or subjects with a clinically significant bleeding disorder.
• Either history of, or a positive serology test at screening for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C antibody (HCAb) and human immunodeficiency virus (HIV) or a negative test at screening for anti-varicella zoster virus (VZV) IgG or hepatitis surface antibody (HBsAb).
• \. Subjects with a history of or a positive screening test for tuberculosis. 14. Subjects who have received a live attenuated vaccination within 12 weeks prior to screening or intend to receive such a vaccine within the course of the study.
• \. Uncontrolled glaucoma, diabetes mellitus, or hypertension. 16. History of any malignancy requiring treatment. 17. History or detection of significant arrhythmia during screening. 18. Subjects with uncontrolled cardiac failure, unstable chest pain, or heart attack deemed significant in the past 6 months.
• \. History of acute myocarditis or presence of acute myocarditis during screening.
• \. Prior treatment with any gene therapy medicinal product. 21. Known or suspected intolerance to gadolinium, tacrolimus and other macrolides, steroids, local anesthetics used for skin or renal biopsies, or any non-investigational medicinal products (NIMPs) or their excipients.
• \. Subjects with contraindications to MRI. Including subjects with ferromagnetic metallic implants, including pacing and defibrillator devices, nerve stimulators and cochlear implants.

Sponsors & Collaborators

• Spur Therapeutics: lead

Study Sites (13)

Kaiser Permanente

Los Angeles, California, 90027, United States

Location

Columbia University

New York, New York, 10032, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Lysosomal and Rare Disorders Research and Treatment Center

Fairfax, Virginia, 22030, United States

Location

Medical University of Vienna

Vienna, Austria

Location

Metabolics and Genetics in Calgary (MAGIC Clinic)

Calgary, Toronto, T2E 7Z4, Canada

Location

Charité - Universitätsmedizin Berlin

Berlin, Germany

Location

UKEA University Hospital Hamburg

Hamburg, Germany

Location

University of Würzburg

Würzburg, Germany

Location

Universita Federico II di Napoli

Napoli, Italy

Location

Haukeland University Hospital

Bergen, Norway

Location

Royal Free Hospital

London, United Kingdom

Location

Salford Royal NHS Foundation Trust

Salford, United Kingdom

Location

Related Publications (1)

• Jeyakumar JM, Kia A, Tam LCS, McIntosh J, Spiewak J, Mills K, Heywood W, Chisari E, Castaldo N, Verhoef D, Hosseini P, Kalcheva P, Cocita C, Miranda CJ, Canavese M, Khinder J, Rosales C, Hughes D, Sheridan R, Corbau R, Nathwani A. Preclinical evaluation of FLT190, a liver-directed AAV gene therapy for Fabry disease. Gene Ther. 2023 Jun;30(6):487-502. doi: 10.1038/s41434-022-00381-y. Epub 2023 Jan 11.

  PMID: 36631545 DERIVED

MeSH Terms

Conditions

Fabry Disease; Lysosomal Storage Diseases

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2019
• First Posted: July 31, 2019
• Study Start: July 8, 2019
• Primary Completion: May 2, 2023
• Study Completion: May 2, 2023
• Last Updated: June 5, 2023

Record last verified: 2023-04

Locations

NO (1); GB (2); AU (1); DE (3); CA (1); US (4); IT (1)