Fabry DiseasePhase 1/2NCT03454893
Open Label, Study Of Efficacy and Safety Of AVR-RD-01 for Treatment-Naive Subjects With Classic Fabry Disease
A Phase 1/2 study testing AVR-RD-01 in people with Fabry Disease, run by AVROBIO at 5 sites in 3 countries.
Trial summary
This was a multinational, open-label study to assess the efficacy and safety of AVR-RD-01 in approximately 15 male subjects, who were 16 years of age or older and postpubertal with a confirmed diagnosis of classic Fabry disease based on deficient alpha galactosidase A (AGA) enzyme activity who were considered… Read more about this study
- Who is it for?
- Ages 16 to 50 years, men only
- Conditions the study is for
- Fabry Disease
- What is being tested?
- AVR-RD-01
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 5 sitesin 3 countries
- Study dates
- 21 Feb 2018to 14 Mar 2022
- 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 16 to 50 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Subject was male, 16 years of age or older (18 years of age or older in the US), and post pubertal,(minimum age by region)
- Subject had a confirmed diagnosis of classic Fabry disease based on deficient AGA enzyme activity (defined as < 1% of normal).
Who cannot join
- Subject had a galactosidase alpha (GLA) gene mutation associated with late-onset cardiac variant Fabry disease.
- Subject had previously received ERT and/or chaperone therapy within 3 years for treatment of Fabry disease.
- Subject had tested positive for anti-AGA antibodies at the time of screening.
- Subject had eGFR < 60 mL/min/1.73 m² (ie, chronic kidney disease [CKD] stage ≥ 3) at Screening.
- Subject had a prior history of myocardial infarction (MI).
- Subject had a history of coronary artery disease (CAD) with angina requiring percutaneous transluminal coronary angioplasty (with or without stent placement) and/or coronary artery bypass graft (CABG).
Show all 15Show fewer
- Subject had a history of moderate to severe valvular heart disease requiring valve replacement.
- Subject had a history of heart failure, moderate to severe diastolic dysfunction, and/or left ventricular ejection fraction (LVEF) ≤ 45% on echocardiogram (ECHO) performed at rest at Screening.
- Subject had a history of clinically significant cardiac arrhythmia (eg, heart block [second or third degree], atrial fibrillation requiring therapy, ventricular fibrillation, ventricular tachycardia, supraventricular tachycardia, or cardiac arrest).
- Note [history of intermittent atrial fibrillation not requiring treatment was allowed].
- Subject had a prior history of stroke and/or transient ischemic attack (TIA).
- Subject had aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≥ 3 times the upper limit of normal (ULN) at Screening.
- Subject had a prior history of (or current) malignancy; the one exception is a prior history of resected basal cell carcinoma.
- Subject had previously received treatment with AVR-RD-01 or any other gene therapy.
- Other inclusion/exclusion criteria apply.
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
United States2 sites
Hackensack University Medical Center
Hackensack, New Jersey, 07601
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Australia2 sites
Royal Melbourne Hospital
Melbourne, Parkville VIC
Royal Perth Hospital
Perth
Brazil1 site
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul
About this study
Official title: An Open-Label, Multinational Study Of The Efficacy And Safety of Ex Vivo, Lentiviral Vector-Mediated Gene Therapy AVR-RD-01 For Treatment-Naive Subjects With Classic Fabry Disease
This was a multinational, open-label study to assess the efficacy and safety of AVR-RD-01 in approximately 15 male subjects, who were 16 years of age or older and postpubertal with a confirmed diagnosis of classic Fabry disease based on deficient alpha galactosidase A (AGA) enzyme activity who were considered treatment naïve, i.e., had not previously received treatment with enzyme replacement therapy (ERT) and/or chaperone therapy within 3 years of the time of Screening.
Read the detailed description
The duration of each subject's participation in this study was approximately 64 weeks (or 1 year, 12 weeks), comprised of five study periods (Screening, Baseline, Pre-transplant, Transplant, and Post-transplant Follow-up). During the Screening Period (approximately 8 weeks), written informed consent (and assent, if applicable) was obtained and the subject had completed other Screening procedures to confirm study eligibility. Once study eligibility was confirmed, the subjects entered the Baseline Period (up to 3 days) during which time assessments would have been performed to establish a pre-transplant baseline. Once baseline assessments were completed, the subject entered the Pre-transplant Period (approximately 6 weeks) during which time mobilization, apheresis, AVR-RD-01 investigational drug product preparation and testing for release, and conditioning regimen administration to achieve myeloablation took place. Following completion of the Pre-transplant Period, the subject entered the Transplant Period (1 day) during which time AVR-RD-01 infusion took place. After AVR-RD-01 infusion, the subject entered the Post-transplant Follow-up Period (approximately 48 weeks), during which time periodic safety and efficacy assessments were performed to assess measures of engraftment, clinical response, and safety post-transplant.
In January 2022, the study was terminated early due to a decision by the study sponsor, to deprioritize its Fabry disease development program, and therefore, some subjects (n=5) did not complete the study (i.e., Week 48). Subsequently, in August 2023, the long-term follow-up study (AVRO-RD-01-LTF01), was also terminated early due to the decision by the sponsor to terminate the development program for Fabry disease, and therefore, no subjects completed the 15-year long-term follow-up study. This decision to terminate was not based on any safety or medical reasons.
- Conditions
- Fabry Disease
- Being tested
- AVR-RD-01
- Keywords
- Fabry disease, Cell therapy, Gene therapy, Lysosomal storage disorder, Lenti-viral
- Medical subject headings
- Fabry Disease, Lysosomal Storage Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AVR-RD-01Drug
Single IV infusion of between 3 - 20 x 10^6 CD34+ cells/kg.
| Study group | Role | What they receive |
|---|---|---|
| Single Assignment AVR-RD-01 | Experimental | AVR-RD-01 is an autologous CD34+-enriched cell fraction transduced with LV/AGA containing an RNA transcript that, after reverse transcription, results in codon-optimized cDNA that, upon its integration into the human genome, encodes for functional human AGA. Receives: Drug: AVR-RD-01 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
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). Of the 13 serious adverse events, no SAEs reported were considered related to AVR RD 01. Of the 354 adverse events, no AEs were considered related to AVR RD 01. The SAEs and AEs reported in the study were attributed to the conditioning agent used, the underlying disease, comorbid conditions, study procedures and concomitant medications.
Measured: Baseline to Week 48 post gene therapy
Change From Baseline in Immunogenicity of AVR-RD-01
Number of subjects with changes in anti-AGA antibodies from Baseline to post infusion timepoints. Unite 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 compare to Baseline) indicates no immune response to the therapeutic protein.
Measured: Baseline to Week 48 post gene therapy
Presence of Replication Competent Lentivirus (RCL)
The "Presence of RCL" is a theoretical risk of lentiviral gene therapy treatment based on the theory that it may be possible for inadvertent generation of RCL caused either by recombination of the lentiviral vector plasmids during the vector production process or by mobilization of proviral DNA in vivo by infectious retroviruses (HIV). The absence of RCL is a positive indicator of safety.
Measured: Baseline to Week 48 post gene therapy
Evaluation of Aberrant Clonal Expansion
Integration Site Analysis (ISA) uses next generation sequencing to identify junction sites between the integrated therapeutic transgene and the host genome. Samples are analyzed for the emergence of clonality (defined as (a single clone accounting for greater than 20% of the population) and whether any integration site is within or near a known oncogene.
Measured: Baseline to Week 48 post gene therapy
Change From Baseline in the Average Number of Gb3 Inclusions (ie, Myelinosomes) Per Kidney Peritubular Capillary (PTC) Per Subject
Globotriaosylceramide (Gb3) Inclusions in Peritubular Capillaries (PTC) on Kidney Biopsy. Electron microscopic images of kidney biopsy samples were taken and read centrally by two independent renal pathologists, each of whom scored the average number of Gb3 inclusions per kidney PTC per subject using a quantification method. Healthy renal tissue would have no Gb3 inclusions. A reduction from baseline is desirable.
Measured: Baseline to Week 48 post gene therapy
Secondary outcomes (14)
Average Vector Copy Number (VCN) in Peripheral Blood Leukocytes as Assessed by Quantitative Polymerase Chain Reaction (qPCR) and/or Droplet Digital Polymerase Chain Reaction (ddPCR)
Vector Copy Number (VCN) is a measurement of the number of copies of the therapeutic transgene 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.
Measured: At Week 24 and Week 48 post gene therapy
Change From Baseline (CFB) in AGA Enzyme Activity Level in Plasma and Peripheral Blood Leukocytes (PBLs)
Treatment-naïve Fabry patients are deficient in alpha-galactosidase A (AGA) enzyme activity due to mutations in the GLA gene. Any therapeutic option offered should aim to increase the amount of available AGA enzyme. This assay measured the AGA enzyme activity levels in plasma and PBLs. It should be noted that the measurement in plasma reflects the amount of "free" AGA enzyme that has been released from cells into the extracellular space and is therefore considered a more indirect measure of AGA enzyme activity, compared to the result in PBLs which is more of a direct measure of enzyme within cells. In both cases, enzyme activity is expected to increase from Baseline to the post-infusion timepoints.
Measured: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Globotriaosylceramide (Gb3) Biomarkers for Fabry Disease in Plasma
Globotriaosylceramide (Gb3) is the substrate that accumulates in the lysosomes of patients affected by Fabry Disease as a result of deficiencies in AGA enzyme activity. Treatment-naive patients are expected to have high levels of Gb3 in their lysosomes and correspondingly elevated levels in plasma. Treatment with AVR-RD-01 is intended to replace the missing AGA enzymatic activity, which allows degradation of accumulated Gb3 substrate in the lysosomes and reductions in the levels of circulating Gb3 in plasma.
Measured: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Globotriaosylceramide (Gb3) Biomarkers for Fabry Disease in Urine
Globotriaosylceramide (Gb3) is the substrate that accumulates in the lysosomes of patients affected by Fabry Disease as a result of deficiencies in AGA enzyme activity. Treatment-naive patients are expected to have high levels of Gb3 in their lysosomes and correspondingly elevated levels in urine. Treatment with AVR-RD-01 is intended to replace the missing AGA enzymatic activity, which allows degradation of accumulated Gb3 substrate in the lysosomes and reductions in the levels of excreted Gb3 in urine.
Measured: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Substrate (i.e. Gb3) in Skin Biopsy
Globotriaosylceramide (Gb3) is the substrate that accumulates in the lysosomes of patients affected by Fabry Disease as a result of deficiencies in AGA enzyme activity. Treatment-naive patients are expected to have high levels of Gb3 in their lysosomes and correspondingly elevated levels in tissue samples. Treatment with AVR-RD-01 is intended to replace the missing AGA enzymatic activity, which allows degradation of accumulated Gb3 substrate in the lysosomes and reductions in the levels of measured Gb3 in tissues.
Measured: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Renal Function as Assessed by Measured Glomerular Filtration Rate (mGFR)
mGFR is a measure of the time the kidney takes to filter products that the body does not naturally produce.
Measured: Baseline to Week 48 post gene therapy
Change From Baseline in Renal Function as Assessed by Estimated Glomerular Filtration Rate (eGFR)
eGFR is the measure to evaluate kidney function. It is the estimated amount of blood that is filtered through all glomeruli in a given time.
Measured: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Renal Function as Assessed by Urine Total Protein Levels
Measured: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Renal Function as Assessed by Urine Albumin Levels
A healthy kidney only allows very small amounts of albumin to pass from the blood into the urine. An increased level of albumin in urine (albuminuria) is a marker of renal damage.
Measured: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Left Ventricular Mass Index (LVMI) as Assessed by Cardiac Magnetic Resonance Imaging (MRI)
LVMI is a surrogate of left ventricular hypertrophy. An increase in LVMI is an independent risk factor for cardiovascular morbidity and mortality.
Measured: Baseline to Week 48 post gene therapy
Change From Baseline in Abdominal Pain and Stool Consistency as Assessed by the Diary for Irritable Bowel Syndrome Symptoms-Diarrhea (DIBSS-D)
DIBSS-D assesses bowel habits and abdominal symptoms over a period of time. It was administered daily for 14 days commencing at each study visit.
Stool Consistency scale has been converted to a numeric rating scale for ease of analysis, where 1=Very hard; 2=Hard; 3=Neither too hard nor too soft; 4=Loose but not lumpy; 5=Very loose and watery. The median of each 14-day period was derived per patient, per visit before deriving the group median. Group median at Baseline (pre-treatment) was 3.540 (n=9). Change from baseline (CFB) is presented below. An increase CFB indicates softening of the stools, and a decrease CFB indicates hardening of the stools. Abdominal Pain measure asked the patient to rate the worst level of pain within the past 24hrs (0=no pain; 10=worst possible pain). A mean score was derived for each 14-day period per patient, per visit, and these means used to derive a group mean. An increase CFB indicates more abdominal pain; a decrease CFB indicates less abdominal pain.
Measured: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Brief Pain Inventory-Short Form (BPI-SF) Questionnaire Scores
The short version of the BPI (Short form) includes 9 items: Q1 - Q9, Question 9 includes 7 sub-items (Q9a - Q9g). It uses a 0 to 10 numeric rating scales for item rating. The pain severity score is calculated as the average of questions answered: Q3 (worst pain), Q4 (least pain), Q5 (average pain) and Q6 (current pain). The pain interference score is calculated as the average of the answered Q9 sub-items, which represents pain interference with general activity (Q9a), mood (Q9b), walking ability (Q9c), normal work (Q9d), relations with other people (Q9e), sleep (Q9f), and enjoyment of life (Q9g). A reduction in score from baseline indicates less pain.
Measured: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Physical and Mental Functioning as Assessed by the Short Form 36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores
The original version of the SF-36 was administered to the participants and consisted of eight subscales (Vitality, Physical Functioning, Bodily Pain, General Health Perceptions, Physical Role Functioning, Emotional Role Functioning, Social Role Functioning and Mental Health) each scored from 0 (worst health) to 100 (best heath). These scores were normalized (re-scaled) against mean scores obtained in the US general population (Mean=50, Standard deviation 10). The summary health components PCS and MCS are derived from the eight subscales mentioned above and summarize information from all eight subscales but with different weights. For PCS, highest weights are given to the physical subscales while some mental subscales are given negative weights. For MCS, highest weights are given to the mental subscales while some physical subscales are given negative weights. An increase in the normalized score from baseline indicates improvement in physical and mental functioning.
Measured: Baseline to Week 48 post gene therapy
Average Vector Copy Number (VCN) in Bone Marrow / Progenitor Cells as Assessed by Quantitative Polymerase Chain Reaction (qPCR) and/or Droplet Digital Polymerase Chain Reaction (ddPCR)
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: At Week 48 post gene therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2018
- Study start21 Feb 2018
- Primary completion14 Mar 2022
- Study completion14 Mar 2022
Why it stopped: AVROBIO has deprioritized its Fabry disease program
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 Fabry 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- AVROBIO
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Inderpal Panesar, MRPharmS, Study director, AVROBIO, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03454893
- Sponsor's protocol ID
- AVRO-RD-01-201
- Status last verified
- Sep 2023
- First submitted
- 20 Dec 2017
- Last updated
- 5 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 5 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multinational Study Of The Efficacy And Safety of Ex Vivo, Lentiviral Vector-Mediated Gene Therapy AVR-RD-01 For Treatment-Naive Subjects With Classic Fabry Disease
- ClinicalTrials.gov ID
- NCT03454893
- Acronym / sponsor ID
- AVRO-RD-01-201
- Conditions
- Fabry Disease
- Keywords
- Fabry disease, Cell therapy, Gene therapy, Lysosomal storage disorder, Lenti-viral
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: AVROBIO has deprioritized its Fabry disease program
- Enrolment
- 15 participants (actual)
- Lead sponsor
- AVROBIOIndustry (pharma, biotech, devices)
- Study start
- 21 Feb 2018 (actual)
- Primary completion
- 14 Mar 2022 (actual)
- Study completion
- 14 Mar 2022 (actual)
- First posted
- 6 Mar 2018 (actual)
- Results
- Posted 5 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 efficacy and safety of AVR-RD-01 in approximately 15 male subjects, who were 16 years of age or older and postpubertal with a confirmed diagnosis of classic Fabry disease based on deficient alpha galactosidase A (AGA) enzyme activity who were considered treatment naïve, i.e., had not previously received treatment with enzyme replacement therapy (ERT) and/or chaperone therapy within 3 years of the time of Screening.
Detailed description
The duration of each subject's participation in this study was approximately 64 weeks (or 1 year, 12 weeks), comprised of five study periods (Screening, Baseline, Pre-transplant, Transplant, and Post-transplant Follow-up). During the Screening Period (approximately 8 weeks), written informed consent (and assent, if applicable) was obtained and the subject had completed other Screening procedures to confirm study eligibility. Once study eligibility was confirmed, the subjects entered the Baseline Period (up to 3 days) during which time assessments would have been performed to establish a pre-transplant baseline. Once baseline assessments were completed, the subject entered the Pre-transplant Period (approximately 6 weeks) during which time mobilization, apheresis, AVR-RD-01 investigational drug product preparation and testing for release, and conditioning regimen administration to achieve myeloablation took place. Following completion of the Pre-transplant Period, the subject entered the Transplant Period (1 day) during which time AVR-RD-01 infusion took place. After AVR-RD-01 infusion, the subject entered the Post-transplant Follow-up Period (approximately 48 weeks), during which time periodic safety and efficacy assessments were performed to assess measures of engraftment, clinical response, and safety post-transplant.
In January 2022, the study was terminated early due to a decision by the study sponsor, to deprioritize its Fabry disease development program, and therefore, some subjects (n=5) did not complete the study (i.e., Week 48). Subsequently, in August 2023, the long-term follow-up study (AVRO-RD-01-LTF01), was also terminated early due to the decision by the sponsor to terminate the development program for Fabry disease, and therefore, no subjects completed the 15-year long-term follow-up study. This decision to terminate was not based on any safety or medical reasons.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Assignment AVR-RD-01 | Experimental | Drug: AVR-RD-01AVR-RD-01 is an autologous CD34+-enriched cell fraction transduced with LV/AGA containing an RNA transcript that, after reverse transcription, results in codon-optimized cDNA that, upon its integration into the human genome, encodes for functional human AGA. |
Who may qualify
- Ages
- 16 to 50 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Subject was male, 16 years of age or older (18 years of age or older in the US), and post pubertal,(minimum age by region)
- Subject had a confirmed diagnosis of classic Fabry disease based on deficient AGA enzyme activity (defined as < 1% of normal).
Key exclusion criteria (15 listed)
- Subject had a galactosidase alpha (GLA) gene mutation associated with late-onset cardiac variant Fabry disease.
- Subject had previously received ERT and/or chaperone therapy within 3 years for treatment of Fabry disease.
- Subject had tested positive for anti-AGA antibodies at the time of screening.
- Subject had eGFR < 60 mL/min/1.73 m² (ie, chronic kidney disease [CKD] stage ≥ 3) at Screening.
- Subject had a prior history of myocardial infarction (MI).
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-01Single IV infusion of between 3 - 20 x 10^6 CD34+ cells/kg. | Drug | Single Assignment AVR-RD-01 |
Primary outcome
Incidence of and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Baseline to Week 48 post gene therapy
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). Of the 13 serious adverse events, no SAEs reported were considered related to AVR RD 01. Of the 354 adverse events, no AEs were considered related to AVR RD 01. The SAEs and AEs reported in the study were attributed to the conditioning agent used, the underlying disease, comorbid conditions, study procedures and concomitant medications.
Change From Baseline in Immunogenicity of AVR-RD-01
Time frame: Baseline to Week 48 post gene therapy
Number of subjects with changes in anti-AGA antibodies from Baseline to post infusion timepoints. Unite 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 compare to Baseline) indicates no immune response to the therapeutic protein.
Presence of Replication Competent Lentivirus (RCL)
Time frame: Baseline to Week 48 post gene therapy
The "Presence of RCL" is a theoretical risk of lentiviral gene therapy treatment based on the theory that it may be possible for inadvertent generation of RCL caused either by recombination of the lentiviral vector plasmids during the vector production process or by mobilization of proviral DNA in vivo by infectious retroviruses (HIV). The absence of RCL is a positive indicator of safety.
Evaluation of Aberrant Clonal Expansion
Time frame: Baseline to Week 48 post gene therapy
Integration Site Analysis (ISA) uses next generation sequencing to identify junction sites between the integrated therapeutic transgene and the host genome. Samples are analyzed for the emergence of clonality (defined as (a single clone accounting for greater than 20% of the population) and whether any integration site is within or near a known oncogene.
Change From Baseline in the Average Number of Gb3 Inclusions (ie, Myelinosomes) Per Kidney Peritubular Capillary (PTC) Per Subject
Time frame: Baseline to Week 48 post gene therapy
Globotriaosylceramide (Gb3) Inclusions in Peritubular Capillaries (PTC) on Kidney Biopsy. Electron microscopic images of kidney biopsy samples were taken and read centrally by two independent renal pathologists, each of whom scored the average number of Gb3 inclusions per kidney PTC per subject using a quantification method. Healthy renal tissue would have no Gb3 inclusions. A reduction from baseline is desirable.
14 secondary outcomes
Average Vector Copy Number (VCN) in Peripheral Blood Leukocytes as Assessed by Quantitative Polymerase Chain Reaction (qPCR) and/or Droplet Digital Polymerase Chain Reaction (ddPCR)
Time frame: At Week 24 and Week 48 post gene therapy
Change From Baseline (CFB) in AGA Enzyme Activity Level in Plasma and Peripheral Blood Leukocytes (PBLs)
Time frame: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Globotriaosylceramide (Gb3) Biomarkers for Fabry Disease in Plasma
Time frame: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Globotriaosylceramide (Gb3) Biomarkers for Fabry Disease in Urine
Time frame: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Substrate (i.e. Gb3) in Skin Biopsy
Time frame: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Renal Function as Assessed by Measured Glomerular Filtration Rate (mGFR)
Time frame: Baseline to Week 48 post gene therapy
Change From Baseline in Renal Function as Assessed by Estimated Glomerular Filtration Rate (eGFR)
Time frame: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Renal Function as Assessed by Urine Total Protein Levels
Time frame: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Renal Function as Assessed by Urine Albumin Levels
Time frame: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Left Ventricular Mass Index (LVMI) as Assessed by Cardiac Magnetic Resonance Imaging (MRI)
Time frame: Baseline to Week 48 post gene therapy
Change From Baseline in Abdominal Pain and Stool Consistency as Assessed by the Diary for Irritable Bowel Syndrome Symptoms-Diarrhea (DIBSS-D)
Time frame: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Brief Pain Inventory-Short Form (BPI-SF) Questionnaire Scores
Time frame: Baseline to Week 24 and Week 48 post gene therapy
Change From Baseline in Physical and Mental Functioning as Assessed by the Short Form 36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores
Time frame: Baseline to Week 48 post gene therapy
Average Vector Copy Number (VCN) in Bone Marrow / Progenitor Cells as Assessed by Quantitative Polymerase Chain Reaction (qPCR) and/or Droplet Digital Polymerase Chain Reaction (ddPCR)
Time frame: At Week 48 post gene therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 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.
Inderpal Panesar, MRPharmS study director
AVROBIO, Inc
5 sites in 3 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-01 in people with Fabry Disease, run by AVROBIO at 5 sites in 3 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 2 inclusion and 15 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 5 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, Australia, Brazil. 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 5 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?
Incidence of and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Baseline to Week 48 post gene therapy). The study lists 5 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 5 Jan 2024.