search
Back to results

A Fabry Disease Gene Therapy Study (MARVEL1)

Primary Purpose

Fabry Disease, Lysosomal Storage Diseases

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
FLT190
Sponsored by
Freeline Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fabry Disease focused on measuring Gene Therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Kaiser Permanente
  • Columbia University
  • UPMC Children's Hospital of Pittsburgh
  • Lysosomal and Rare Disorders Research and Treatment Center
  • Medical University of Vienna
  • Metabolics and Genetics in Calgary (MAGIC Clinic)
  • Charité - Universitätsmedizin Berlin
  • UKEA University Hospital Hamburg
  • University of Würzburg
  • Universita Federico II di Napoli
  • Haukeland University Hospital
  • Royal Free Hospital
  • Salford Royal NHS Foundation Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

FLT190

Arm Description

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

Outcomes

Primary Outcome Measures

Frequency of treatment-emergent adverse events (AEs)
To investigate the safety of systemic administration of FLT190.

Secondary Outcome Measures

Full Information

First Posted
July 26, 2019
Last Updated
June 2, 2023
Sponsor
Freeline Therapeutics
search

1. Study Identification

Unique Protocol Identification Number
NCT04040049
Brief Title
A Fabry Disease Gene Therapy Study
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Terminated
Why Stopped
Freeline has decided to pause development of FLT190 in Fabry disease to focus its resources on advancing FLT201.
Study Start Date
July 8, 2019 (Actual)
Primary Completion Date
May 2, 2023 (Actual)
Study Completion Date
May 2, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Freeline Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fabry Disease, Lysosomal Storage Diseases
Keywords
Gene Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FLT190
Arm Type
Experimental
Arm Description
FLT190 is a recombinant adeno- associated viral (AAV) vector. Administered by a single intravenous infusion.
Intervention Type
Genetic
Intervention Name(s)
FLT190
Intervention Description
Gene Therapy product.
Primary Outcome Measure Information:
Title
Frequency of treatment-emergent adverse events (AEs)
Description
To investigate the safety of systemic administration of FLT190.
Time Frame
From screening to 12 weeks post infusion

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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). Willingness to avoid strenuous exercise during first 3 months after dosing. Exclusion Criteria: 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. 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.
Facility Information:
Facility Name
Kaiser Permanente
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
UPMC Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Lysosomal and Rare Disorders Research and Treatment Center
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22030
Country
United States
Facility Name
Medical University of Vienna
City
Vienna
Country
Austria
Facility Name
Metabolics and Genetics in Calgary (MAGIC Clinic)
City
Calgary
State/Province
Toronto
ZIP/Postal Code
T2E 7Z4
Country
Canada
Facility Name
Charité - Universitätsmedizin Berlin
City
Berlin
Country
Germany
Facility Name
UKEA University Hospital Hamburg
City
Hamburg
Country
Germany
Facility Name
University of Würzburg
City
Würzburg
Country
Germany
Facility Name
Universita Federico II di Napoli
City
Napoli
Country
Italy
Facility Name
Haukeland University Hospital
City
Bergen
Country
Norway
Facility Name
Royal Free Hospital
City
London
Country
United Kingdom
Facility Name
Salford Royal NHS Foundation Trust
City
Salford
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

A Fabry Disease Gene Therapy Study

We'll reach out to this number within 24 hrs