Last reviewed · How we verify

NCT04145037

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

Terminated Phase 1, PHASE2 Results posted Last updated 18 January 2024
What this trial tests

Phase 1, PHASE2 trial testing AVR-RD-02 in Gaucher Disease in 8 participants. Terminated before completion.

Timeline
30 May 2019
Primary endpoint
21 August 2023
21 August 2023

Quick facts

Lead sponsorAVROBIO
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment8
Start date30 May 2019
Primary completion21 August 2023
Estimated completion21 August 2023
Sites5 locations across Canada, United States

Drugs / interventions tested

Conditions studied

Sponsor

AVROBIO — full company profile →

Who can join

Adults 18 to 50, any sex, with Gaucher Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Clinically Significant Adverse Events (AEs) and Serious Adverse Events (SAEs) of AVR-RD-02 Primary · Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

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 o

SAEs Related to AVR-RD-02 Infusion
GroupValue95% CI
Switch Stable0
AEs Related to AVR-RD-02 Infusion
GroupValue95% CI
Switch Stable0
SAEs Not Related to AVR-RD-02 Infusion
GroupValue95% CI
Switch Stable2
AEs Not Related to AVR-RD-02 Infusion
GroupValue95% CI
Switch Stable189
Vector Copy Number (VCN) in Peripheral Blood as Assessed by Quantitative Polymerase Chain Reaction (qPCR) and/or Droplet Digital Polymerase Chain Reaction (ddPCR) Primary · Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

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.

GroupValue95% CI
Switch Stable0.550.17 – 0.86
Change From Baseline in Spleen Volume Assessed by Abdominal MRI Primary · Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

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.

GroupValue95% CI
Switch Stable-17.03-22.8 – -10.9
Change From Baseline in Liver Volume Assessed by Abdominal MRI Primary · Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

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.

GroupValue95% CI
Switch Stable-4.95-21.1 – 7.8
Change From Baseline in Hemoglobin Concentration Primary · Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

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.

GroupValue95% CI
Switch Stable1.000.87 – 1.14
Change From Baseline in Platelet Count Primary · Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

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.

GroupValue95% CI
Switch Stable0.830.64 – 1.08
Change From Baseline in Plasma Lyso-Gb1 Levels by Liquid Chromatography Tandem Mass Spectrometry (LC/MS/MS) Primary · Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

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.

GroupValue95% CI
Switch Stable-12.03-29.50 – -0.50
Change From Baseline in GCase Enzyme Activity Level in Plasma Secondary · Weeks 13, 26, 39, and 52

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.

Week 13
GroupValue95% CI
Switch Stable7.61.8 – 10.9
Week 26
GroupValue95% CI
Switch Stable5.04.0 – 5.9
Week 39
GroupValue95% CI
Switch Stable4.91.7 – 8.4
Week 52
GroupValue95% CI
Switch Stable1.5-1.8 – 3.6
Change From Baseline in GCase Enzyme Activity Level in Peripheral Blood Leukocytes Secondary · Weeks 13, 26, 39, and 52

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.

Week 13
GroupValue95% CI
Switch Stable13.311.0 – 15.6
Week 26
GroupValue95% CI
Switch Stable19.219.2 – 19.2
Week 39
GroupValue95% CI
Switch Stable6.00.6 – 13.2
Week 52
GroupValue95% CI
Switch Stable7.10.2 – 11.5
Number of Subjects Who Restarted ERT Secondary · Between Week 26 and Week 52 post-AVR-RD-02 treatment

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

GroupValue95% CI
Switch Stable0
Change From Baseline in Presence of Anti-GCase Total Antibodies Secondary · At Weeks 5, 13, 26, 39, and 52

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.

Week 5
GroupValue95% CI
Switch Stable0
Week 13
GroupValue95% CI
Switch Stable0
Week 26
GroupValue95% CI
Switch Stable0
Week 39
GroupValue95% CI
Switch Stable0
Week 52
GroupValue95% CI
Switch Stable0
Change From Baseline in Bone Mineral Density (BMD) Assessed by Bone Density Scan (DXA) Secondary · Baseline to 52 weeks post-AVR-RD-02 treatment follow-up

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

Femoral Neck Bone Mineral Density
GroupValue95% CI
Switch Stable0.00.0 – 0.0
Lumbar Spine Bone Mineral Density (maximum)
GroupValue95% CI
Switch Stable0.0-0.7 – 0.7

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to week 52. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Switch Stable
Serious: 2/6 (33%)
Deaths: 0/6
Treatment-naïve
Serious: 0
Deaths: 0

Serious adverse events (2 terms)

ReactionSystemSwitch StableTreatment-naïve
Febrile neutropeniaBlood and lymphatic system disorders
PancreatitisGastrointestinal disorders
Other adverse events (73 terms — click to expand)

ReactionSystemSwitch StableTreatment-naïve
AnaemiaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
Neutrophil count decreasedInvestigations
White blood cell count decreasedInvestigations
AlopeciaSkin and subcutaneous tissue disorders
Febrile neutropeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
Mucosal inflammationGeneral disorders
Lymphocyte count decreasedInvestigations
Platelet count decreasedInvestigations
FatigueGeneral disorders
Bone painMusculoskeletal and connective tissue disorders
DysgeusiaNervous system disorders
HeadacheNervous system disorders
ThrombocytopeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
Catheter site painGeneral disorders
Amylase increasedInvestigations
Blood lactate dehydrogenase increasedInvestigations
Lipase increasedInvestigations
Weight decreasedInvestigations
DehydrationMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
PancreatitisGastrointestinal disorders
StomatitisGastrointestinal disorders
Catheter site erythemaGeneral disorders
Non-cardiac chest painGeneral disorders
PainGeneral disorders
PyrexiaGeneral disorders
SwellingGeneral disorders
HyperbilirubinaemiaHepatobiliary disorders
BacteraemiaInfections and infestations
Skin infectionInfections and infestations
ContusionInjury, poisoning and procedural complications

Most-reported serious reactions: Febrile neutropenia, Pancreatitis.

Data from ClinicalTrials.gov NCT04145037 adverse events section.

Sponsor's own description

This was a multinational, open-label study to assess the safety and efficacy of AVR-RD-02 in approximately 8 to 16 subjects (male or female) who are ≥18 and ≤50 years of age and post pubertal at Screening with a confirmed diagnosis of Type 1 Gaucher disease (based on clinical phenotype, genotyping, and deficient GCase enzyme activity in whole blood).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Current Clinical Applications of In Vivo Gene Therapy with AAVs.
    Mendell JR, Al-Zaidy SA, Rodino-Klapac LR, Goodspeed K, et al · · 2021 · cited 544× · PMID 33309881 · DOI 10.1016/j.ymthe.2020.12.007
  2. Diagnosing neuronopathic Gaucher disease: New considerations and challenges in assigning Gaucher phenotypes.
    Daykin EC, Ryan E, Sidransky E. · · 2021 · cited 51× · PMID 33483255 · DOI 10.1016/j.ymgme.2021.01.002
  3. Immunological barriers to haematopoietic stem cell gene therapy.
    Charlesworth CT, Hsu I, Wilkinson AC, Nakauchi H. · · 2022 · cited 47× · PMID 35301483 · DOI 10.1038/s41577-022-00698-0
  4. Therapeutic Approaches in Lysosomal Storage Diseases.
    Fernández-Pereira C, San Millán-Tejado B, Gallardo-Gómez M, Pérez-Márquez T, et al · · 2021 · cited 43× · PMID 34944420 · DOI 10.3390/biom11121775
  5. Gene Therapy for Lysosomal Storage Disorders: Ongoing Studies and Clinical Development.
    Massaro G, Geard AF, Liu W, Coombe-Tennant O, et al · · 2021 · cited 42× · PMID 33924076 · DOI 10.3390/biom11040611
  6. Gene therapy for inherited metabolic diseases.
    Yilmaz BS, Gurung S, Perocheau D, Counsell J, et al · · 2020 · cited 19× · PMID 33554501 · DOI 10.34763/jmotherandchild.20202402si.2004.000009
  7. Gene Therapy of Sphingolipid Metabolic Disorders.
    Shaimardanova AA, Solovyeva VV, Issa SS, Rizvanov AA. · · 2023 · cited 18× · PMID 36835039 · DOI 10.3390/ijms24043627
  8. Stem Cells in Clinical Trials on Neurological Disorders: Trends in Stem Cells Origins, Indications, and Status of the Clinical Trials.
    Namiot ED, Niemi JVL, Chubarev VN, Tarasov VV, et al · · 2022 · cited 18× · PMID 36232760 · DOI 10.3390/ijms231911453

Verify or expand the search:

Other recruiting trials for Gaucher Disease

Currently open trials in the same condition.

Other AVROBIO trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04145037.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing