Clinical trial NCT04040049: A Fabry Disease Gene Therapy Study
Official title: A Phase 1/2, Baseline-controlled, Non-randomized, Open-label, Single-ascending Dose Study of a Novel Adeno-associated Viral Vector (FLT190) in Patients With Fabry Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Fabry Disease
Lysosomal Storage Diseases
Keywords: Gene Therapy
Lead sponsor: Spur Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-07-31
Enrollment: 3
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: Patients who provide consent to participate in this study will be screened for eligibility.

Eligible patients will attend the study site on the day prior to infusion (Day -1) for a baseline visit. On Day 0, FLT190 will be administered as a single dose, slow intravenous infusion. Following FLT190 treatment the patient will be discharged from the investigational site and will continue to be monitored at outpatient visits for a period of approximately 9 months; following which, the patient will enter a period of long-term follow-up conducted under a separate protocol.

The study will be conducted in 2 parts;

Part 1: Enrolment of previously treated patients (Dose escalation)

Part 2: Enrolment of previously untreated patients (Dose expansion).

Eligibility criteria: Inclusion Criteria:

1. Adult males, ≥ 18 years of age with classic Fabry disease.
2. Confirmed diagnosis of classic Fabry Disease
3. Decreased plasma alpha galactosidase (αGLA) activity at screening.
4. One or more of the characteristic features of classic Fabry disease.
5. Estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73m2 at screening.
6. \<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
7. Able to give full informed consent and able to comply with all requirements of the trial including the 5-year long term follow-up.
8. Willingness to practice barrier contraception whilst vector shedding via semen is present.
9. Lack of AAV neutralizing antibodies within 6 weeks prior to dosing.
10. For inclusion in Part 1, subjects must have received either a licensed ERT or PCT for at least 12 months prior to dosing. For inclusion in Part 2, subjects must never have been previously dosed with Enzyme Replacement Therapy (ER) or Pharmacological Chaperone Therapy (PCT).
11. Willingness to avoid strenuous exercise during first 3 months after dosing.

Exclusion Criteria:

1. Non-classical Fabry disease.
2. Prior hypersensitivity or intolerance to ERT
3. Prior lack of response to ERT.
4. Subjects with a history of chronic kidney disease for a minimum of 3 months.
5. Subjects with severe myocardial fibrosis.
6. 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
7. Evidence of liver dysfunction as demonstrated by elevated blood levels during screening.
8. Platelet count \< 100 xE9L.
9. Subjects receiving warfarin or other anticoagulants or subjects with a clinically significant bleeding disorder.

10 - 12. 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).

13. 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.

15. 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.

19. History of acute myocarditis or presence of acute myocarditis during screening.

20. 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.

22. Subjects with contraindications to MRI. Including subjects with ferromagnetic metallic implants, including pacing and defibrillator devices, nerve stimulators and cochlear implants.

23. Subjects who have had a renal transplant. 24. Cytomegalovirus immunoglobulin positive subjects who are CMV polymerase chain reaction (PCR) positive at screening.

25-26.History of physical or psychiatric illness that could affect the subject's ability to participate or a history of substance abuse including alcohol abuse.

Primary outcomes:
measure: Frequency of treatment-emergent adverse events (AEs)
timeFrame: From screening to 12 weeks post infusion
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: New York
country: United States
facility: Columbia University
state: New York
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Fairfax
country: United States
facility: Lysosomal and Rare Disorders Research and Treatment Center
state: Virginia
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Calgary
country: Canada
facility: Metabolics and Genetics in Calgary (MAGIC Clinic)
state: Toronto
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Hamburg
country: Germany
facility: UKEA University Hospital Hamburg
city: Würzburg
country: Germany
facility: University of Würzburg
city: Napoli
country: Italy
facility: Universita Federico II di Napoli
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
Study officials:
References: