A Fabry Disease Gene Therapy Study (MARVEL1)

• ClinicalTrials.gov Identifier: NCT04040049
• Recruitment Status: Unknown
• First Posted: July 31, 2019
• Last Update Posted: February 3, 2021
• Sponsor: Freeline Therapeutics
• Information provided by (Responsible Party): Freeline Therapeutics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Fabry Disease; Lysosomal Storage Diseases	Genetic: FLT190	Phase 1; Phase 2

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 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).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2, Baseline-controlled, Non-randomised, Open-label, Single-ascending Dose Study of a Novel Adeno-associated Viral Vector (FLT190) in Patients With Fabry Disease
• Actual Study Start Date: July 8, 2019
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: FLT190; FLT190 is a replication-incompetent adeno- associated viral (AAV) vector. Administered by a single intravenous infusion.	Genetic: FLT190; Gene Therapy product.

Outcome Measures

Primary Outcome Measures :

1. Frequency of treatment-emergent adverse events (AEs) [ Time Frame: From screening to 9 months post infusion ]
   To investigate the safety of systemic administration of FLT190.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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. Elevated plasma LysoGb3 levels at screening (Part 2 only)
6. Estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73m2 at screening.
7. <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
8. Able to give full informed consent and able to comply with all requirements of the trial including long term follow-up.
9. Willingness to practice barrier contraception whilst vector shedding via semen is present.
10. Lack of AAV neutralising antibodies.
11. For inclusion in Part 1, subjects must have received 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 ERT or PCT.

Exclusion Criteria:

1. Non-classical Fabry disease.
2. Presence of antibodies to αGLA, Replagal, or Fabrazyme.
3. Subjects with chronic kidney disease.
4. Subjects with severe myocardial fibrosis.
5. 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
6. Evidence of liver dysfunction.
7. Platelet count < 100 xE9L.
8. Subjects receiving warfarin or other anticoagulants or subjects with a clinically significant bleeding disorder.

9 - 12. Either history of, or a positive serology test at screening for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCAb) and human immunodeficiency virus (HIV) or a negative test at screening for anti-varicella zoster virus (VZV) IgG.

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. Malignancy requiring treatment. 17. Subjects with uncontrolled cardiac failure, unstable angina, or myocardial infarction in the past 6 months.

18. Acute cardiac failure, unstable angina or myocardial infarction in the past 6 months.

19. Prior treatment with any gene transfer medicinal product. 20. Known or suspected intolerance to Replagal, Fabrazyme or any NIMPs used in the study.

21. Subjects with contraindications to MRI. 22. Subjects who have had a renal transplant. 23. Cytomegalovirus immunoglobulin positive subjects who are CMV PCR positive at screening.

24-25.History of physical or psychiatric illness that could affect the subject's ability to participate or a history of substance abuse including alcohol abuse.

Contacts and Locations

Contacts

Contact: Clinical Operations; +44 1438 906870; contact@freeline.life

Locations

Germany

Charité - Universitätsmedizin Berlin; Recruiting

Berlin, Germany

University of Würzburg; Recruiting

Würzburg, Germany

Italy

Universita Federico II di Napoli; Recruiting

Napoli, Italy

Norway

Haukeland University Hospital; Recruiting

Bergen, Norway

United Kingdom

Royal Free Hospital; Recruiting

London, United Kingdom

Sponsors and Collaborators

Freeline Therapeutics

More Information

• Responsible Party: Freeline Therapeutics
• ClinicalTrials.gov Identifier: NCT04040049
• Other Study ID Numbers: FLT190-01
• First Posted: July 31, 2019
• Last Update Posted: February 3, 2021
• Last Verified: February 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Freeline Therapeutics:

Gene Therapy

Additional relevant MeSH terms:

Fabry Disease; Lysosomal Storage Diseases; 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; Metabolic Diseases; Lipid Metabolism Disorders; Sphingolipidoses; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors