A Fabry Disease Gene Therapy Study

Fabry Disease Clinical Trial

— MARVEL1  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04040049
• Other study ID #: FLT190-01
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: July 8, 2019
• Est. completion date: May 2, 2023

Study information

• Verified date: April 2023
• Source: Freeline Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: May 2, 2023
• Est. primary completion date: May 2, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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 (aGLA) 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.

Related Conditions & MeSH terms

• Fabry Disease
• Lysosomal Storage Diseases

Intervention

Genetic:
• FLT190
Gene Therapy product.

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna
Canada	Metabolics and Genetics in Calgary (MAGIC Clinic)	Calgary	Toronto
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	UKEA University Hospital Hamburg	Hamburg
Germany	University of Würzburg	Würzburg
Italy	Universita Federico II di Napoli	Napoli
Norway	Haukeland University Hospital	Bergen
United Kingdom	Royal Free Hospital	London
United Kingdom	Salford Royal NHS Foundation Trust	Salford
United States	Lysosomal and Rare Disorders Research and Treatment Center	Fairfax	Virginia
United States	Kaiser Permanente	Los Angeles	California
United States	Columbia University	New York	New York
United States	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Freeline Therapeutics

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Germany,  Italy,  Norway,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of treatment-emergent adverse events (AEs)	To investigate the safety of systemic administration of FLT190.	From screening to 12 weeks post infusion