Trial Outcomes & Findings for Lentiviral Vector Gene Therapy - The Guard1 Trial of AVR-RD-02 for Subjects With Type 1 Gaucher Disease (NCT NCT04145037)

Last Updated: 2024-01-18

Results Overview

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The AE/SAE are also inclusive of any abnormalities in Clinical Laboratory Tests, Vital Signs and in Electrocardiographs (ECGs). AE/SAE can either be related to AVR-RD-02 infusion or attributed to the conditioning agent, mobilization agent(s), study procedures, and the underlying disease.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

8 participants

Primary outcome timeframe

Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

Results posted on

2024-01-18

Participant Flow

Participant milestones

Participant milestones
Measure	Switch Stable Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e, any combination of infusions resulting in a total monthly ERT do.se of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note : No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Overall Study STARTED	8	0
Overall Study Mobilized and Apheresed	6	0
Overall Study Received AVR-RD-02	5	0
Overall Study COMPLETED	4	0
Overall Study NOT COMPLETED	4	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Switch Stable Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e, any combination of infusions resulting in a total monthly ERT do.se of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note : No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Overall Study Study terminated	2	0
Overall Study Withdrawal by Subject	1	0
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

Lentiviral Vector Gene Therapy - The Guard1 Trial of AVR-RD-02 for Subjects With Type 1 Gaucher Disease

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

Population: Population consists of switch-stable subjects. Treatment-naïve arm did not enroll any subjects at the time of study termination.

Outcome measures

Outcome measures
Measure	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note: No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Switch Stable n=6 Participants Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e, any combination of infusions resulting in a total monthly ERT dose of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Number of Clinically Significant Adverse Events (AEs) and Serious Adverse Events (SAEs) of AVR-RD-02 SAEs Related to AVR-RD-02 Infusion	—	0 Number of events
Number of Clinically Significant Adverse Events (AEs) and Serious Adverse Events (SAEs) of AVR-RD-02 AEs Related to AVR-RD-02 Infusion	—	0 Number of events
Number of Clinically Significant Adverse Events (AEs) and Serious Adverse Events (SAEs) of AVR-RD-02 SAEs Not Related to AVR-RD-02 Infusion	—	2 Number of events
Number of Clinically Significant Adverse Events (AEs) and Serious Adverse Events (SAEs) of AVR-RD-02 AEs Not Related to AVR-RD-02 Infusion	—	189 Number of events

PRIMARY outcome

Timeframe: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

Population: Population consists of switch-stable subjects. Treatment-naïve arm did not enroll any subjects at the time of study termination.

VCN, defined as the average number of copies of the therapeutic gene (transgene) in a sample of cells, is conventionally reported as the number of vector copies found in a sample, relative to copies of a reference gene in the human genome. This is an estimate of the number of integration sites per cell (on average). A VCN of 1 would signify that a sample of cells evaluated contains on average at least one \[working\] copy of the therapeutic transgene per cell. This measurement was for VCN in a sample of progenitor cells obtained from a peripheral blood sample.

Outcome measures

Outcome measures
Measure	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note: No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Switch Stable n=4 Participants Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e, any combination of infusions resulting in a total monthly ERT dose of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Vector Copy Number (VCN) in Peripheral Blood as Assessed by Quantitative Polymerase Chain Reaction (qPCR) and/or Droplet Digital Polymerase Chain Reaction (ddPCR)	—	0.55 number of copies/cell Interval 0.17 to 0.86

PRIMARY outcome

Timeframe: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

Population: Population consists of switch-stable subjects. Bone marrow samples were collected and batched for analysis, but due to the early termination of the study, samples were not analyzed and subsequently discarded. Refer to "Limitations and Caveats" section. Treatment-naïve arm did not enroll any subjects at the time of study termination.

VCN is defined as the average number of copies of the therapeutic gene (transgene) in a sample of cells and is a measurement of the number of copies of the vector found in a sample, relative to copies of a reference gene in the human genome. This is an estimate of the number of integration sites per cell (on average). A VCN of 1 would signify that a sample of cells evaluated contains on average at least one \[working\] copy of the therapeutic transgene per cell. This measurement was for VCN in a sample of bone marrow progenitor cells obtained from an aspirate.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

Population: Population consists of switch-stable subjects. Of the four participants who completed the study, one participant had been splenectomized. Treatment-naïve arm did not enroll any subjects at the time of study termination.

Percent change in spleen volume = (\[spleen volume at Week 52 minus spleen volume at baseline\] divided by \[spleen volume at baseline\]) multiplied by 100. A reduction in the percent change from baseline (%CFB) in spleen volume (mL) is a positive indicator of efficacy.

Outcome measures

Outcome measures
Measure	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note: No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Switch Stable n=3 Participants Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e, any combination of infusions resulting in a total monthly ERT dose of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Change From Baseline in Spleen Volume Assessed by Abdominal MRI	—	-17.03 percentage Interval -22.8 to -10.9

PRIMARY outcome

Timeframe: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

Population: Population consists of switch-stable subjects. Treatment-naïve arm did not enroll any subjects at the time of study termination.

Percent change in liver volume = (\[liver volume at Week 52 minus liver volume at baseline\] divided by \[liver volume at baseline\]) multiplied by 100. A reduction in the percent change from baseline (%CFB) in liver volume (mL) is a positive indicator of efficacy.

Outcome measures

Outcome measures
Measure	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note: No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Switch Stable n=4 Participants Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e, any combination of infusions resulting in a total monthly ERT dose of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Change From Baseline in Liver Volume Assessed by Abdominal MRI	—	-4.95 percentage Interval -21.1 to 7.8

PRIMARY outcome

Timeframe: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

Population: Population consists of switch-stable subjects. Treatment-naïve arm did not enroll any subjects at the time of study termination.

Ratio to baseline indicates the percent change in hemoglobin concentration. The baseline value is defined as 1 or 100%. A ratio to Baseline \<1 indicates a reduction in hemoglobin concentration and a ratio to Baseline \>1 indicates an increase in hemoglobin concentration.

Outcome measures

Outcome measures
Measure	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note: No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Switch Stable n=4 Participants Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e, any combination of infusions resulting in a total monthly ERT dose of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Change From Baseline in Hemoglobin Concentration	—	1.00 ratio Interval 0.87 to 1.14

PRIMARY outcome

Timeframe: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

Population: Population consists of switch-stable subjects. Treatment-naïve arm did not enroll any subjects at the time of study termination.

Ratio to baseline indicates the percent change in platelet count. The Baseline value is defined as 1 or 100%. A ratio to Baseline \<1 indicates a reduction in platelet count and a ratio to Baseline \>1 indicates an increase in platelet count.

Outcome measures

Outcome measures
Measure	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note: No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Switch Stable n=4 Participants Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e, any combination of infusions resulting in a total monthly ERT dose of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Change From Baseline in Platelet Count	—	0.83 ratio Interval 0.64 to 1.08

PRIMARY outcome

Timeframe: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

Population: Population consists of switch-stable subjects. Treatment-naïve arm did not enroll any subjects at the time of study termination.

Glucosylsphingosine (lyso-Gb1) is the substrate that accumulates in the lysosomes of patients affected by Gaucher disease as a result of deficiencies in GCase enzyme activity. Treatment with AVR-RD-02 is intended to replace the missing GCase enzymatic activity, which allows degradation of accumulated lyso-Gb1 substrate in the lysosomes. Negative values (decrease from Baseline) are an indicator of efficacy.

Outcome measures

Outcome measures
Measure	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note: No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Switch Stable n=4 Participants Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e, any combination of infusions resulting in a total monthly ERT dose of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Change From Baseline in Plasma Lyso-Gb1 Levels by Liquid Chromatography Tandem Mass Spectrometry (LC/MS/MS)	—	-12.03 ng/mL Interval -29.5 to -0.5

SECONDARY outcome

Timeframe: Weeks 13, 26, 39, and 52

Population: Population consists of switch-stable subjects. Treatment-naïve arm did not enroll any subjects at the time of study termination

Treatment-naïve Gaucher patients are deficient in glucosylcerebrosidase (GCase) enzyme activity due to mutations in the GBA gene. AVR-RD-02 is intended to increase the amount of GCase enzyme activity in the lysosomes of treated subjects. A positive value (increase from Baseline in GCase enzyme activity) is a positive indicator of efficacy.

Outcome measures

Outcome measures
Measure	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note: No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Switch Stable n=4 Participants Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e, any combination of infusions resulting in a total monthly ERT dose of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Change From Baseline in GCase Enzyme Activity Level in Plasma Week 13	—	7.6 μmol/L/h Interval 1.8 to 10.9
Change From Baseline in GCase Enzyme Activity Level in Plasma Week 26	—	5.0 μmol/L/h Interval 4.0 to 5.9
Change From Baseline in GCase Enzyme Activity Level in Plasma Week 39	—	4.9 μmol/L/h Interval 1.7 to 8.4
Change From Baseline in GCase Enzyme Activity Level in Plasma Week 52	—	1.5 μmol/L/h Interval -1.8 to 3.6

SECONDARY outcome

Timeframe: Weeks 13, 26, 39, and 52

Population: Population consists of switch-stable subjects. Although samples were collected, GCase PBL results were not available at many timepoints due to sample instability, and therefore, only available results are reported in the table below. Refer to "Limitations and Caveats" section. Treatment-naïve arm did not enroll any subjects at the time of study termination

Outcome measures

Outcome measures
Measure	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note: No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Switch Stable n=4 Participants Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e, any combination of infusions resulting in a total monthly ERT dose of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Change From Baseline in GCase Enzyme Activity Level in Peripheral Blood Leukocytes Week 13	—	13.3 μmol/g protein/h Interval 11.0 to 15.6
Change From Baseline in GCase Enzyme Activity Level in Peripheral Blood Leukocytes Week 26	—	19.2 μmol/g protein/h Interval 19.2 to 19.2
Change From Baseline in GCase Enzyme Activity Level in Peripheral Blood Leukocytes Week 39	—	6.0 μmol/g protein/h Interval 0.6 to 13.2
Change From Baseline in GCase Enzyme Activity Level in Peripheral Blood Leukocytes Week 52	—	7.1 μmol/g protein/h Interval 0.2 to 11.5

SECONDARY outcome

Timeframe: Between Week 26 and Week 52 post-AVR-RD-02 treatment

Population: Population consists of switch-stable subjects. Treatment-naïve arm did not enroll any subjects at the time of study termination.

The absence of the need to re-start ERT post treatment is a positive indicator of efficacy.

Outcome measures

Outcome measures
Measure	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note: No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Switch Stable n=5 Participants Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e, any combination of infusions resulting in a total monthly ERT dose of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Number of Subjects Who Restarted ERT	—	0 Participants

SECONDARY outcome

Timeframe: At Weeks 5, 13, 26, 39, and 52

Population: Population consists of switch-stable subjects. One of the five subjects had pre-existing antibodies to GCase due to ERT exposure. This subject had a positive and unchanged low titer at all pre-infusion and post-infusion timepoints. Treatment-naïve arm did not enroll at the time of study termination

Number of subjects with changes in anti-GCase antibodies from Baseline to post infusion timepoints. Unit of measure: Number of subjects negative at baseline but positive at post-treatment timepoints. A negative or zero result (titer lower or unchanged at post-infusion timepoints compared to Baseline) indicates no immune response to the therapeutic protein.

Outcome measures

Outcome measures
Measure	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note: No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Switch Stable n=5 Participants Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e, any combination of infusions resulting in a total monthly ERT dose of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Change From Baseline in Presence of Anti-GCase Total Antibodies Week 5	—	0 Participants
Change From Baseline in Presence of Anti-GCase Total Antibodies Week 13	—	0 Participants
Change From Baseline in Presence of Anti-GCase Total Antibodies Week 26	—	0 Participants
Change From Baseline in Presence of Anti-GCase Total Antibodies Week 39	—	0 Participants
Change From Baseline in Presence of Anti-GCase Total Antibodies Week 52	—	0 Participants

SECONDARY outcome

Timeframe: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

Population: Population consists of switch-stable subjects. Some subjects had missing baseline and/or Week 52 data, and therefore change from baseline could not be calculated. Refer to "Limitations and Caveats" section. Treatment-naïve arm did not enroll any subjects at the time of study termination.

An increase in BMD is a positive indicator of efficacy. Subjects had T-scores reported for change from baseline in Bone Mineral Density in the Femoral Neck and Lumbar Spine regions assessed by Bone Mineral Density (DXA). The T-score on the subject's bone density report shows how many standard deviations the subject's bone mass differs from the bone mass of an average healthy 30-year-old adult. If the bones are more dense than the average 30-year-old adult, the bone mass will be indicated as a positive T-score. Higher positive T-score indicates greater bone density. If the bones are less dense than the average 30-year-old adult, the bone mass will be indicated as a negative T-score. Lower negative T-score indicates lesser bone density.

Outcome measures

Outcome measures
Measure	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note: No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Switch Stable n=2 Participants Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e, any combination of infusions resulting in a total monthly ERT dose of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Change From Baseline in Bone Mineral Density (BMD) Assessed by Bone Density Scan (DXA) Femoral Neck Bone Mineral Density	—	0.0 T-score Interval 0.0 to 0.0
Change From Baseline in Bone Mineral Density (BMD) Assessed by Bone Density Scan (DXA) Lumbar Spine Bone Mineral Density (maximum)	—	0.0 T-score Interval -0.7 to 0.7

SECONDARY outcome

Timeframe: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

An increase in BMD is a positive indicator of efficacy. Subjects had Z-scores reported for change from baseline in Bone Mineral Density in the Femoral Neck and Lumbar Spine regions assessed by Bone Mineral Density (DXA). A Z-score compares the subject's bone density to the average bone density of people their own age and gender. If the bones more dense than the average person their own age and gender, the bone mass will be indicated as a positive Z-score. Higher positive Z-score indicates greater bone density. If the bones are less dense than the average person their own age and gender, the bone mass will be indicated as a negative Z-score. Lower negative Z-score indicates lesser bone density.

Outcome measures

Outcome measures
Measure	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note: No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Switch Stable n=3 Participants Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e, any combination of infusions resulting in a total monthly ERT dose of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Change From Baseline in Bone Mineral Density (BMD) Assessed by Bone Density Scan (DXA) Femoral Neck Bone Mineral Density	—	0.45 Z-score Interval 0.2 to 0.7
Change From Baseline in Bone Mineral Density (BMD) Assessed by Bone Density Scan (DXA) Lumbar Spine Bone Mineral Density	—	-0.13 Z-score Interval -0.7 to 0.2

SECONDARY outcome

Timeframe: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

Population: Population consists of switch-stable subjects. Treatment-naïve arm do not enroll any subjects at the time of study termination. The secondary efficacy clinical outcome measure was not evaluated as originally planned. (Refer to "Limitations and Caveats" Section.)

Chitotriosidase enzyme is part of an inflammatory response originating in macrophages, which are the primary cell type affected in Gaucher disease. Gaucher disease patients typically have elevated Chitotriosidase enzyme activity in their plasma compared to healthy population. A reduction from Baseline in chitotriosidase enzyme activity is a positive indicator of efficacy.

Outcome measures

Outcome measures
Measure	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note: No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Switch Stable n=2 Participants Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e, any combination of infusions resulting in a total monthly ERT dose of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Change From Baseline in Plasma Chitotriosidase Activity Levels Measured by Fluorometric Enzyme Assay	—	-37.8 μmol/L/h Interval -70.4 to -5.1

SECONDARY outcome

Timeframe: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

Population: Population consists of switch-stable subjects. Treatment-naïve arm did not enroll any subjects at the time of study termination.

Bone Marrow Burden Score is a semi-quantitative MRI scoring system for assessing the extent of bone marrow involvement in Gaucher disease. A BMB score from 0 to 8 could be given for the lumbar spine, and a BMB score from 0 to 8 could be given to the femurs. Thus, a total BMB score of up to 16 is obtained by adding the lumbar and femoral BMB scores. A higher total BMB-score indicates more severe bone marrow involvement. A reduction in BMB score is a positive indicator of efficacy.

Outcome measures

Outcome measures
Measure	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note: No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Switch Stable n=4 Participants Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e, any combination of infusions resulting in a total monthly ERT dose of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Change From Baseline in Bone Marrow Burden (BMB) Score as Assessed by Bone Magnetic Resonance Imaging (MRI)	—	0.5 Change from baseline score Interval -1.0 to 1.0

Adverse Events

Switch Stable

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Treatment-naïve

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Switch Stable n=6 participants at risk Switch-stable arm: Subjects who have undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; ie, any combination of infusions resulting in a total monthly ERT dose of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must discontinue ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who have been on ERT and substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who have never received either ERT or SRT for Gaucher disease or have not received either ERT or SRT for Gaucher disease within 12 months of Screening (ie, treatment-naïve subjects). Enrollment will follow a similar scheme as for the switch-stable subjects. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).
Blood and lymphatic system disorders Febrile neutropenia	16.7% 1/6 • Up to week 52 An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience; persistent or significant disability/incapacity; congenital anomaly. The AE/SAE are also inclusive of any abnormalities in Clinical Laboratory Tests, Vital Signs and ECGs.	— 0/0 • Up to week 52 An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience; persistent or significant disability/incapacity; congenital anomaly. The AE/SAE are also inclusive of any abnormalities in Clinical Laboratory Tests, Vital Signs and ECGs.
Gastrointestinal disorders Pancreatitis	16.7% 1/6 • Up to week 52 An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience; persistent or significant disability/incapacity; congenital anomaly. The AE/SAE are also inclusive of any abnormalities in Clinical Laboratory Tests, Vital Signs and ECGs.	— 0/0 • Up to week 52 An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience; persistent or significant disability/incapacity; congenital anomaly. The AE/SAE are also inclusive of any abnormalities in Clinical Laboratory Tests, Vital Signs and ECGs.

Other adverse events

Additional Information

AVROBIO MedInfo

AVROBIO, Inc

Phone: 617-914-8419

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Switch Stable n=8 Participants Switch-stable arm: Subjects who had undergone ERT ≥15 U/kg and ≤60 U/kg every other week (or equivalent; i.e., any combination of infusions resulting in a total monthly ERT do.se of \>30 U/kg and \<120 U/kg) for ≥24 consecutive months for Type 1 Gaucher disease at the time of Screening. Switch-stable subjects must have discontinued ERT at least 2 weeks before the scheduled transplant day. Switch-stable subjects who had been on substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Treatment-naïve Treatment-naïve arm: Subjects with Type 1 Gaucher disease who had never received either ERT or SRT for Gaucher disease or had not received either ERT or SRT for Gaucher disease within 12 months of Screening (i.e., treatment-naïve subjects). Enrollment followed a similar scheme as for the switch-stable subjects. Note : No subjects enrolled in this arm. AVR-RD-02: AVR-RD-02 Drug product: active substance is autologous CD34+ enriched hematopoietic stem cells (HSCs) that have been genetically modified ex vivo with a lentiviral vector (LV) to contain a ribonucleic acid (RNA) transcript that, after reverse transcription, results in codon-optimized, complementary deoxyribonucleic acid (cDNA) that, upon its integration into human genome, encodes for functional human glucocerebrosidase (GCase).	Total n=8 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	0 Participants n=7 Participants	8 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	34.25 years STANDARD_DEVIATION 6.30 • n=5 Participants	—	34.25 years STANDARD_DEVIATION 6.30 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	0 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	0 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants