Clinical trial NCT04836377: A Long-Term Follow-up Study of Subjects With Gaucher Disease Who Previously Received AVR-RD-02
Official title: A Long-Term Follow-up Study of Subjects With Gaucher Disease Who Previously Received AVR-RD-02
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Type 1 Gaucher Disease
Keywords: Gaucher
Guard1
Lead sponsor: AVROBIO
Sponsor class: INDUSTRY
First posted: 2021-04-08
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: To permit longitudinal assessment of safety, efficacy and durability of effect of AVR-RD-02 gene therapy infusion in the AVRO-RD-02-LTF01 study, subjects must have received AVR-RD-02 in a preceding treatment study and agree to comply with the study visit schedule and procedures for AVRO-RD-02-LTF01 for inclusion in the Long-Term Follow-Up study.

Brief summary: This is a multicenter, multinational long-term follow-up study to assess the long-term safety and durability of effect of AVR-RD-02 treatment in subjects who previously received AVR-RD-02 treatment (single dose administration).

Detailed description: Subjects who received AVR-RD-02 in the preceding treatment study and who meet all eligibility criteria may participate in the AVRO-RD-02-LTF01 study. For individual participating subjects, the Baseline visit for the AVRO-RD-02-LTF01 study will coincide with the subject's last visit in the preceding treatment study, whenever feasible. Subjects will be asked to return for study visits at approximately 6-month intervals for the first 4 years of the study and then annually thereafter for 10 years (for a total follow-up of 14 years in this study), during which time periodic safety and efficacy assessments will be performed to assess measures of safety, engraftment, and clinical response after AVR-RD-02 treatment.

Eligibility criteria: Inclusion Criteria:

* Subject must have been enrolled and received AVR-RD-02 as single dose administration
* Subject must be willing and able to provide written informed consent for the AVRO-RD-02-LTF01 study in accordance with applicable regulations and guidelines and to comply with all study visits and procedures.

Exclusion Criteria:

* Subject is currently enrolled in an AVROBIO-sponsored AVR-RD-02 treatment study.

Primary outcomes:
measure: Change from baseline over time in spleen volume as assessed by abdominal Magnetic Resonance Imaging (MRI)
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Baseline over time in liver volume as assessed by abdominal MRI
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Baseline over time in hemoglobin
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Change from Baseline over time in platelet count
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Change from Baseline in plasma lyso-Gb1 levels by liquid chromatography tandem mass spectrometry (LC/MS/MS)
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Incidence of newly-diagnosed malignancy, hematologic disorder, and/or immune related events/immunogenicity
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: Number of participants with clinically relevant abnormalities, as assessed by physical examinations findings
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 electrocardiograms (ECGs)
timeFrame: Baseline to Year 15 post gene therapy infusion
Secondary outcomes:
measure: Change from baseline over time in glucocerebrosidase (GCase) GCase enzyme activity level in
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Change from baseline over time in Enzyme Replacement Therapy (ERT) frequency and dosing
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Changes in Gaucher biomarker indices of Gaucher disease in chitotriosidase enzyme activity levels in plasma
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Changes in Gaucher biomarker indices of Gaucher disease in bone marrow burden (BMB) score as assessed by bone MRI
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Changes in Gaucher biomarker indices of Gaucher disease in bone mineral density (BMD) as assessed by dual-energy X-ray absorptiometry (DXA)
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Average Vector Copy Number (VCN) in bone marrow aspirate 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 anti-GCase total antibodies and subsequent titers by an electrochemiluminescence method
timeFrame: Baseline to Year 15 post gene therapy infusion
measure: Changes in Gaucher disease in potential aberrant clonal expansion(s) assessed by performing insertional site analysis (ISA)
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
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Calgary
country: Canada
facility: M.A.G.I.C. Clinic Ltd
state: Calgary Alberta
Study officials:
affiliation: AVROBIO
name: Milena Veselinovic, MD
role: STUDY_DIRECTOR
References: