Clinical trial NCT04999059: Long-Term Follow-up Study of Subjects With Fabry Disease Who Received Lentiviral Gene Therapy in Study AVRO-RD-01-201
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
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Fabry Disease
Keywords: Fabry Disease
Cell therapy
Gene therapy
Long-term follow-up
Lysosomal storage disorder
Lenti-viral
Lead sponsor: AVROBIO
Sponsor class: INDUSTRY
First posted: 2021-08-10
Enrollment: 5
Sex: MALE
Minimum age (years): 16
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of clinically significant AEs and SAEs
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Number of participants with clinically relevant abnormalities, as assessed by clinical laboratory tests
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Number of participants with clinically relevant abnormalities, as assessed by vital signs
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Presence of anti-Alpha-galactosidase A (AGA) antibodies
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Presence of replication competent lentivirus (RCL)
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Evaluate for the presence of aberrant clonal expansion as assessed by integration site analysis (ISA)
timeFrame: Baseline to Year 15 post gene therapy infusion
Secondary outcomes:
measure: Change from baseline in AGA enzyme activity level and peripheral blood leukocytes (PBLs)
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: 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)
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Change from baseline in Globotriaosylceramide (Gb3) biomarkers for Fabry disease in plasma and urine
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: 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)
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Change from baseline in eGFR
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Change from baseline in left ventricular mass index (LVMI) as assessed by cardiac magnetic resonance imaging (MRI)
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Change from baseline in abdominal pain and stool consistency as assessed by the Diary for Irritable Bowel Syndrome Symptoms-Diarrhea (DIBSS-D)
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Change from baseline in Brief Pain Inventory-Short Form (BPI-SF) questionnaire scores
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: 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
timeFrame: Baseline to Year 15 post gene therapy infusion
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Parkville VIC
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Grande Do Sul
Study officials:
affiliation: AVROBIO, Inc
name: Inderpal Panesar, MRPharmS
role: STUDY_DIRECTOR
References: