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

Fabry Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04999059
• Other study ID #: AVRO-RD-01-LTF01
• Status: Terminated
• Start date: May 8, 2019
• Est. completion date: August 16, 2023

Study information

• Verified date: October 2022
• Source: AVROBIO
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: August 16, 2023
• Est. primary completion date: August 16, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 16 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fabry Disease

Intervention

Other:
• Safety and Efficacy Assessments
Safety evaluations, disease-specific assessments, and other assessments to monitor for long-term complications of gene therapy intervention.

Locations

Country	Name	City	State
Australia	Royal Melbourne Hospital	Melbourne	Parkville VIC
Australia	Royal Perth Hospital	Perth
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul

Sponsors (1)

Lead Sponsor	Collaborator
AVROBIO

Countries where clinical trial is conducted

Australia,  Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of clinically significant AEs and SAEs		Baseline to Year 15 post gene therapy infusion
Primary	Number of participants with clinically relevant abnormalities, as assessed by clinical laboratory tests		Baseline to Year 15 post gene therapy infusion
Primary	Number of participants with clinically relevant abnormalities, as assessed by vital signs		Baseline to Year 15 post gene therapy infusion
Primary	Presence of anti-Alpha-galactosidase A (AGA) antibodies		Baseline to Year 15 post gene therapy infusion
Primary	Presence of replication competent lentivirus (RCL)		Baseline to Year 15 post gene therapy infusion
Primary	Evaluate for the presence of aberrant clonal expansion as assessed by integration site analysis (ISA)		Baseline to Year 15 post gene therapy infusion
Secondary	Change from baseline in AGA enzyme activity level and peripheral blood leukocytes (PBLs)		Baseline to Year 15 post gene therapy infusion
Secondary	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
Secondary	Change from baseline in Globotriaosylceramide (Gb3) biomarkers for Fabry disease in plasma and urine		Baseline to Year 15 post gene therapy infusion
Secondary	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
Secondary	Change from baseline in eGFR		Baseline to Year 15 post gene therapy infusion
Secondary	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
Secondary	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
Secondary	Change from baseline in Brief Pain Inventory-Short Form (BPI-SF) questionnaire scores		Baseline to Year 15 post gene therapy infusion
Secondary	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