Long-Term Follow-up Study of Subjects With Fabry Disease Who Received Lentiviral Gene Therapy in Study AVRO-RD-01-201

A Long-Term Follow-Up Study of Subjects With Fabry Disease Who Previously Received Ex-Vivo, Lentiviral Vector-Mediated Gene-Modified Autologous Cell Therapy AVR-RD-01 in Study AVRO-RD-01-201

This is a multinational, long-term follow-up study to assess the long-term safety and durability of AVR-RD-01 treatment in participants who received a single dose administration of lentiviral gene therapy in Study AVRO-RD-01-201 (treatment study). No investigational product will be administered in this study. Participants will continue periodic safety and efficacy assessments in this long-term follow-up study up to 15 years from AVR-RD-01 gene therapy infusion.

Study Overview

• Status: Terminated
• Conditions: Fabry Disease
• Intervention / Treatment: Other: Safety and Efficacy Assessments

Detailed Description

Participants enrolled in the AVRO-RD-01-201 study will be offered participation in the AVRO-RD-01-LTF01 study. The Baseline visit for the AVRO-RD-01-LTF01 study will coincide with the participant's last visit in the AVRO-RD-01-201 study. Participants confirmed eligible for the AVRO-RD-01-LTF01 study will be asked to return for study visits at approximately 6-month intervals for the first 4 years and annually thereafter for 10 years (for a total of 15 years from AVR-RD-01 infusion) during which time continued safety, engraftment, and efficacy of treatment will be assessed.

• Study Type: Observational
• Enrollment (Actual): 5

Contacts and Locations

Study Locations

• Australia
  • Perth, Australia
    • Royal Perth Hospital
  • Parkville VIC
    • Melbourne, Parkville VIC, Australia
      • Royal Melbourne Hospital
• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90420-020
      • Hospital de Clinicas de Porto Alegre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects who received AVR-RD-01 in the preceding treatment study, meet all eligibility criteria, and agree to comply with the study visit schedule and procedures.

Description

Inclusion Criteria:

1. Subject must have been enrolled and received AVR-RD-01 in the AVRO-RD-01-201 study.

Exclusion Criteria:

1. Subject has any medical, psychological, or other condition that, in the opinion of the Investigator:

   • Might interfere with the subject's participation in the study (including consenting to procedures); and/or
   • Poses any additional risk to the subject; and/or
   • Might confound the results of any study-required assessments.
2. Subject is currently enrolled in an AVROBIO-sponsored AVR-RD-01 treatment study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Participants with Fabry Disease; This is a long-term follow-up study of participants who previously received AVR-RD-01 (single dose administration) in the AVRO-RD-01-201 treatment study. No investigational product will be administered in this study.	Other: Safety and Efficacy Assessments; Safety evaluations, disease-specific assessments, and other assessments to monitor for long-term complications of gene therapy intervention.; Other Names: Gene Therapy Intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with clinically relevant abnormalities, as assessed by clinical laboratory tests	Baseline to Year 15 post gene therapy infusion
Presence of replication competent lentivirus (RCL)	Baseline to Year 15 post gene therapy infusion
Incidence of clinically significant AEs and SAEs	Baseline to Year 15 post gene therapy infusion
Number of participants with clinically relevant abnormalities, as assessed by vital signs	Baseline to Year 15 post gene therapy infusion
Presence of anti-Alpha-galactosidase A (AGA) antibodies	Baseline to Year 15 post gene therapy infusion
Evaluate for the presence of aberrant clonal expansion as assessed by integration site analysis (ISA)	Baseline to Year 15 post gene therapy infusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in AGA enzyme activity level and peripheral blood leukocytes (PBLs)	Baseline to Year 15 post gene therapy infusion
Average Vector Copy Number (VCN) in peripheral blood leukocytes as assessed by quantitative polymerase chain reaction (qPCR) and/or droplet digital polymerase chain reaction (ddPCR)	Baseline to Year 15 post gene therapy infusion
Change from baseline in Globotriaosylceramide (Gb3) biomarkers for Fabry disease in plasma and urine	Baseline to Year 15 post gene therapy infusion
Average Vector Copy Number (VCN) in bone marrow / progenitor cells as assessed by quantitative polymerase chain reaction (qPCR) and/or droplet digital polymerase chain reaction (ddPCR)	Baseline to Year 15 post gene therapy infusion
Change from baseline in eGFR	Baseline to Year 15 post gene therapy infusion
Change from baseline in left ventricular mass index (LVMI) as assessed by cardiac magnetic resonance imaging (MRI)	Baseline to Year 15 post gene therapy infusion
Change from baseline in abdominal pain and stool consistency as assessed by the Diary for Irritable Bowel Syndrome Symptoms-Diarrhea (DIBSS-D)	Baseline to Year 15 post gene therapy infusion
Change from baseline in Brief Pain Inventory-Short Form (BPI-SF) questionnaire scores	Baseline to Year 15 post gene therapy infusion
Change from baseline in physical and mental functioning as assessed by the Short Form 36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores	Baseline to Year 15 post gene therapy infusion

Collaborators and Investigators

• Sponsor: AVROBIO
• Investigators: Study Director: Inderpal Panesar, MRPharmS, AVROBIO, Inc

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2019
• Primary Completion (Actual): August 16, 2023
• Study Completion (Actual): August 16, 2023

Study Registration Dates

• First Submitted: August 4, 2021
• First Submitted That Met QC Criteria: August 4, 2021
• First Posted (Actual): August 10, 2021

Study Record Updates

• Last Update Posted (Actual): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Cell therapy; Gene therapy; Fabry Disease; Long-term follow-up; Lysosomal storage disorder; Lenti-viral
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease
• Other Study ID Numbers: AVRO-RD-01-LTF01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No