Gaucher DiseasePhase 1/2NCT04145037
Lentiviral Vector Gene Therapy - The Guard1 Trial of AVR-RD-02 for Subjects With Type 1 Gaucher Disease
A Phase 1/2 study testing AVR-RD-02 in people with Gaucher Disease, run by AVROBIO at 5 sites in 2 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Gaucher Disease
- What is being tested?
- AVR-RD-02
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 30 May 2019to 21 Aug 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
None listed.
Who cannot join
- Subject had Type 2 or 3 Gaucher disease, had severe neurological signs and symptoms, defined as complete ocular paralysis, overt myoclonus or history of seizures, characteristic of neuronopathic Gaucher disease, or had a tremor, peripheral neuropathy or symptoms of Parkinson's disease.
- Subject had any one of the following:
- Hemoglobin value <9.0 g/dL, or
- Platelet count <70 x 10˄9/L, or
- Spleen volume >10 x normal, or
- Pulmonary hypertension 3. Subject had experienced a prior anaphylactic or anaphylactoid reaction (of any severity) to ERT.
Show all 26Show fewer
- 4. Treatment-naïve subject had history of clinically significant (CS) anti-GCase antibodies.
- 5. Subject had a contraindication to ERT, in the opinion of the Investigator. 6. Subject had a contraindication to HSC transplantation (HSCT), in the opinion of the Investigator.
- 7. Subject presented with iron, folic acid, and/or vitamin B12 deficiency sustained anemia during Screening.
- 8. Subject had idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), thrombocytopenia, anemia, hepatomegaly, splenomegaly, and/or osteoporosis, unrelated to Gaucher disease, in the opinion of the Investigator.
- 9. Subject had a clinical co-morbidity such as neurologic, cardiovascular, pulmonary, hepatic, gastrointestinal, renal, hematologic, endocrine, metabolic, genetic, immunologic, neoplastic, or psychiatric disease, other medical condition(s), or intercurrent illnesses that may have confounded the study results or, in the opinion of the Investigator, may have precluded participation in the study.
- 10. Subject was a pregnant and/or lactating female. 11. Subject was unable to understand the nature, scope, and possible consequences of the study.
- 12. Subject had diabetes mellitus (Type 1 or Type 2). 13. Subject had active, progressive bone necrosis. 14. Subject had an active chronic infection during the Screening, Baseline, or Pre-gene Therapy Infusion Period of the study.
- 15. Subject had an active uncontrolled acute bacterial, viral, fungal, parasitic, or prion-associated infection during the Screening, Baseline, or Pre-gene Therapy Infusion Period of the study.
- 16. Subject had a history of (or current) tuberculosis. 17. Subject tested positive for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV, Type 1 or 2), human T-cell lymphotropic virus (HTLV)-1, HTLV-2, and/or syphilis on Venereal Disease Research Laboratory (VDRL) test, chemiluminescent microplate immunoassay (CMIA), or enzyme immunosorbent assay (EIA) at Screening.
- 18. Subject had a prior history of (or current) cancer or precancerous lesion or has a known genetic predisposition to cancer. The one exception was a prior history of resected squamous cell carcinoma.
- 19. Subject had any other medical condition that predisposes him/her to (or conveys increased risk of) malignancy, in the opinion of the Investigator - including history of (or current) monoclonal gammopathy of undetermined significance (MGUS).
- 20. Subject had a history of alcohol or illicit drug abuse, according to the Investigator's judgment.
- 21. Subject had undergone, or was scheduled to undergo, bone marrow transplant, HSC transplant, and/or solid organ transplant. NOTE: Subjects who were otherwise eligible for the study but were scheduled for bone marrow or HSC transplant to treat Type 1 Gaucher disease may have been enrolled in the study (instead of receiving an allogeneic transplant) and undergo gene therapy infusion with AVR-RD-02.
- 22. Subject had white blood cell count (WBC) < 3.0 x 10˄9/L and/or uncorrected bleeding disorder from enrollment (i.e., signing of informed consent at Screening) through the Gene Therapy Infusion Period of the study (i.e., the day of AVR-RD-02 gene therapy infusion).
- 23. Subject had clinically significant immunosuppressive disease or condition, in the opinion of the Investigator, at Screening.
- 24. Subject was on (or requires treatment with) cytotoxic or immunosuppressive agents from 60 days prior to signing informed consent at Screening (i.e., study enrollment) through the Week 52 study visit; the one exception was treatment with cytotoxic or immunosuppressive agents required per protocol for stem cell transplant.
- 25. Subject was on (or requires treatment with) red blood cell (RBC) growth factor (e.g., erythropoietin) from 6 months prior to enrollment (i.e., signing of informed consent at Screening) through the Week 52 study visit.
- 26. Subject had any condition that made it impossible to perform MRI studies. 27. Subject had medical condition(s) and/or was receiving medication(s) that would contraindicate ability to undergo mobilization (including contraindication to granulocyte colony-stimulating factor (G-CSF) and/or plerixafor), apheresis, or conditioning.
- 28. Busulfan was contraindicated for the subject. 29. Subject had previously received treatment with AVR-RD-02 or any other gene therapy.
- 30. Subject was participating in (or plans to participate in) any other investigational drug trial or plans to be exposed to any other investigational agent, device and/or procedure, from 30 days prior to enrollment (i.e., signing of informed consent at Screening) through study completion.
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
Hackensack University Medical Center
Hackensack, New Jersey, 07601
University of Iowa
Iowa City, Iowa, 52242
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
University of California San Diego
San Diego, California, 92103
About this study
Official title: The Guard1 Trial, an Open-Label, Multinational Phase 1/2 Study of the Safety and Efficacy of Ex Vivo, Lentiviral Vector-Mediated Gene Therapy AVR-RD-02 for Subjects With Type 1 Gaucher Disease
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).
Read the detailed description
Five study periods (Screening, Baseline, Pre-gene Therapy Infusion, Gene Therapy Infusion, and Post-gene Therapy Infusion Follow-up) comprised the study. During the Screening Period (approximately 60 days), written informed consent was obtained and the subject completed other Screening procedures to confirm study eligibility. Once study eligibility was confirmed, subjects entered the Baseline Period (up to 7 days) during which time assessments were performed to establish Pre-gene Therapy Infusion baseline. Once baseline assessments were completed, the subject entered the Pre-gene Therapy Infusion Period (approximately 8 to 10 weeks) during which time mobilization, apheresis, AVR-RD-02 investigational product preparation and testing for release, busulfan conditioning regimen administration took place. Enzyme replacement therapy was discontinued at least 2 weeks before the scheduled Gene Therapy Infusion Day. Following completion of the Pre-gene Therapy Infusion Period, the subject entered the Gene Therapy Infusion Period (1 day) during which AVR-RD-02 infusion took place. After AVR-RD-02 Gene Therapy Infusion, the subject entered the Post-gene Therapy Infusion Follow-up Period (approximately 52 weeks) during which time periodic safety and efficacy assessments were performed to assess measures of safety, engraftment, and clinical response following AV-RD-02 infusion.
In August 2023, the study was terminated early by the Sponsor, which was not based on any safety or medical reasons and therefore, one subject did not complete the study (i.e., Week 52). Subsequently, in August 2023, the sponsor's long-term follow-up study (AVRO-RD-02-LTF01), was also terminated early for the same reason as the AVRO-RD-02-201 study, and therefore, no subjects completed the 15-year long-term follow-up study.
- Conditions
- Gaucher Disease
- Being tested
- AVR-RD-02
- Keywords
- Type 1 Gaucher, Guard1
- Medical subject headings
- Gaucher Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AVR-RD-02Drug
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).
| Study group | Role | What they receive |
|---|---|---|
| Switch Stable | Experimental | 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 AVR-RD-02 infusion. Switch-stable subjects who had been and substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. Receives: Drug: AVR-RD-02 |
| Treatment-naïve | Experimental | 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. Receives: Drug: AVR-RD-02 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Clinically Significant Adverse Events (AEs) and Serious Adverse Events (SAEs) of AVR-RD-02
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.
Measured: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up
Vector Copy Number (VCN) in Peripheral Blood as Assessed by Quantitative Polymerase Chain Reaction (qPCR) and/or Droplet Digital Polymerase Chain Reaction (ddPCR)
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.
Measured: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up
Vector Copy Number (VCN) in Bone Marrow as Assessed by Quantitative Polymerase Chain Reaction (qPCR) and/or Droplet Digital Polymerase Chain Reaction (ddPCR)
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.
Measured: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up
Change From Baseline in Spleen Volume Assessed by Abdominal MRI
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.
Measured: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up
Change From Baseline in Liver Volume Assessed by Abdominal MRI
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.
Measured: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up
Change From Baseline in Hemoglobin Concentration
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.
Measured: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up
Change From Baseline in Platelet Count
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.
Measured: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up
Change From Baseline in Plasma Lyso-Gb1 Levels by Liquid Chromatography Tandem Mass Spectrometry (LC/MS/MS)
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.
Measured: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up
Secondary outcomes (8)
Change From Baseline in GCase Enzyme Activity Level in Plasma
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.
Measured: Weeks 13, 26, 39, and 52
Change From Baseline in GCase Enzyme Activity Level in Peripheral Blood Leukocytes
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.
Measured: Weeks 13, 26, 39, and 52
Number of Subjects Who Restarted ERT
The absence of the need to re-start ERT post treatment is a positive indicator of efficacy.
Measured: Between Week 26 and Week 52 post-AVR-RD-02 treatment
Change From Baseline in Presence of Anti-GCase Total Antibodies
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.
Measured: At Weeks 5, 13, 26, 39, and 52
Change From Baseline in Bone Mineral Density (BMD) Assessed by Bone Density Scan (DXA)
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.
Measured: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up
Change From Baseline in Bone Mineral Density (BMD) Assessed by Bone Density Scan (DXA)
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.
Measured: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up
Change From Baseline in Plasma Chitotriosidase Activity Levels Measured by Fluorometric Enzyme Assay
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.
Measured: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up
Change From Baseline in Bone Marrow Burden (BMB) Score as Assessed by Bone Magnetic Resonance Imaging (MRI)
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.
Measured: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2019
- Study start30 May 2019
- Primary completion21 Aug 2023
- Study completion21 Aug 2023
Why it stopped: This study was voluntarily terminated by the sponsor to halt development and was not based on any safety or medical reasons.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Gaucher DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- AVROBIO
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Milena Veselinovic, MD, Study director, AVROBIO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04145037
- Sponsor's protocol ID
- AVRO-RD-02-201
- Status last verified
- Oct 2023
- First submitted
- 27 Aug 2019
- Last updated
- 18 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Guard1 Trial, an Open-Label, Multinational Phase 1/2 Study of the Safety and Efficacy of Ex Vivo, Lentiviral Vector-Mediated Gene Therapy AVR-RD-02 for Subjects With Type 1 Gaucher Disease
- ClinicalTrials.gov ID
- NCT04145037
- Acronym / sponsor ID
- AVRO-RD-02-201
- Conditions
- Gaucher Disease
- Keywords
- Type 1 Gaucher, Guard1
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was voluntarily terminated by the sponsor to halt development and was not based on any safety or medical reasons.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- AVROBIOIndustry (pharma, biotech, devices)
- Study start
- 30 May 2019 (actual)
- Primary completion
- 21 Aug 2023 (actual)
- Study completion
- 21 Aug 2023 (actual)
- First posted
- 30 Oct 2019 (actual)
- Results
- Posted 18 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Five study periods (Screening, Baseline, Pre-gene Therapy Infusion, Gene Therapy Infusion, and Post-gene Therapy Infusion Follow-up) comprised the study. During the Screening Period (approximately 60 days), written informed consent was obtained and the subject completed other Screening procedures to confirm study eligibility. Once study eligibility was confirmed, subjects entered the Baseline Period (up to 7 days) during which time assessments were performed to establish Pre-gene Therapy Infusion baseline. Once baseline assessments were completed, the subject entered the Pre-gene Therapy Infusion Period (approximately 8 to 10 weeks) during which time mobilization, apheresis, AVR-RD-02 investigational product preparation and testing for release, busulfan conditioning regimen administration took place. Enzyme replacement therapy was discontinued at least 2 weeks before the scheduled Gene Therapy Infusion Day. Following completion of the Pre-gene Therapy Infusion Period, the subject entered the Gene Therapy Infusion Period (1 day) during which AVR-RD-02 infusion took place. After AVR-RD-02 Gene Therapy Infusion, the subject entered the Post-gene Therapy Infusion Follow-up Period (approximately 52 weeks) during which time periodic safety and efficacy assessments were performed to assess measures of safety, engraftment, and clinical response following AV-RD-02 infusion.
In August 2023, the study was terminated early by the Sponsor, which was not based on any safety or medical reasons and therefore, one subject did not complete the study (i.e., Week 52). Subsequently, in August 2023, the sponsor's long-term follow-up study (AVRO-RD-02-LTF01), was also terminated early for the same reason as the AVRO-RD-02-201 study, and therefore, no subjects completed the 15-year long-term follow-up study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Switch Stable | Experimental | Drug: AVR-RD-02Switch-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 AVR-RD-02 infusion. Switch-stable subjects who had been and substrate reduction therapy (SRT) must not have received SRT within 12 months of Screening. |
| Treatment-naïve | Experimental | Drug: AVR-RD-02Treatment-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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (26 listed)
- Subject had Type 2 or 3 Gaucher disease, had severe neurological signs and symptoms, defined as complete ocular paralysis, overt myoclonus or history of seizures, characteristic of neuronopathic Gaucher disease, or had a tremor, peripheral neuropathy or symptoms of Parkinson's disease.
- Hemoglobin value <9.0 g/dL, or
- Platelet count <70 x 10˄9/L, or
- Spleen volume >10 x normal, or
- Pulmonary hypertension 3. Subject had experienced a prior anaphylactic or anaphylactoid reaction (of any severity) to ERT.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AVR-RD-02AVR-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). | Drug | Switch Stable, Treatment-naïve |
Primary outcome
Number of Clinically Significant Adverse Events (AEs) and Serious Adverse Events (SAEs) of AVR-RD-02
Time frame: 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 or attributed to the conditioning agent, mobilization agent(s), study procedures, and the underlying disease.
Vector Copy Number (VCN) in Peripheral Blood as Assessed by Quantitative Polymerase Chain Reaction (qPCR) and/or Droplet Digital Polymerase Chain Reaction (ddPCR)
Time frame: 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.
Vector Copy Number (VCN) in Bone Marrow as Assessed by Quantitative Polymerase Chain Reaction (qPCR) and/or Droplet Digital Polymerase Chain Reaction (ddPCR)
Time frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up
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.
Change From Baseline in Spleen Volume Assessed by Abdominal MRI
Time frame: 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.
Change From Baseline in Liver Volume Assessed by Abdominal MRI
Time frame: 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.
Change From Baseline in Hemoglobin Concentration
Time frame: 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.
Change From Baseline in Platelet Count
Time frame: 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.
Change From Baseline in Plasma Lyso-Gb1 Levels by Liquid Chromatography Tandem Mass Spectrometry (LC/MS/MS)
Time frame: 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.
8 secondary outcomes
Change From Baseline in GCase Enzyme Activity Level in Plasma
Time frame: Weeks 13, 26, 39, and 52
Change From Baseline in GCase Enzyme Activity Level in Peripheral Blood Leukocytes
Time frame: Weeks 13, 26, 39, and 52
Number of Subjects Who Restarted ERT
Time frame: Between Week 26 and Week 52 post-AVR-RD-02 treatment
Change From Baseline in Presence of Anti-GCase Total Antibodies
Time frame: At Weeks 5, 13, 26, 39, and 52
Change From Baseline in Bone Mineral Density (BMD) Assessed by Bone Density Scan (DXA)
Time frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up
Change From Baseline in Bone Mineral Density (BMD) Assessed by Bone Density Scan (DXA)
Time frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up
Change From Baseline in Plasma Chitotriosidase Activity Levels Measured by Fluorometric Enzyme Assay
Time frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up
Change From Baseline in Bone Marrow Burden (BMB) Score as Assessed by Bone Magnetic Resonance Imaging (MRI)
Time frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Milena Veselinovic, MD study director
AVROBIO
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AVR-RD-02 in people with Gaucher Disease, run by AVROBIO at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Clinically Significant Adverse Events (AEs) and Serious Adverse Events (SAEs) of AVR-RD-02 (time frame: Baseline to 52 weeks post-AVR-RD-02 treatment follow-up). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2024.