A Phase 1/2 interventional study of AVR-RD-01 in Fabry Disease, sponsored by AVROBIO. Terminated at 5 sites in 3 countries. Open to male participants aged 16 Years to 50 Years. Per ClinicalTrials.gov, last updated 2024-01-05.
Sponsored by AVROBIO · Phase 1/2, Interventional, and Treatment
Among 94 studies in Fabry Disease with a site in United States — 13 open to participants now, 18 under way, 6 of them phase 3. Fabry Disease · United States.
Among the 94 studies in Fabry Disease with a site in United States, this one is the 41st largest by enrollment of the 58 interventional ones that give a count, is one of 7 that started in 2018, is one of 7 in phase 1/2, and was the 62nd registered.
244 studies on the registry are indexed under Fabry Disease; 55 are open to participants now.
Browse Fabry Disease studies →13 of the 94 studies in Fabry Disease with a site in United States are open now. Recruiting first, the newest first:
Idorsia Pharmaceuticals Ltd. · Sites in United States, Canada, France and 2 more countries
Ages 18–60 · Men only
Amicus Therapeutics · Sites in United States
Ages 18+
Amicus Therapeutics · Sites in United States, Belgium, Germany and 3 more countries
Ages 2–11
Chiesi Farmaceutici S.p.A. · Sites in United States, Austria, France and 3 more countries
Ages 2–17
Chiesi Farmaceutici S.p.A. · Sites in United States, Germany, Italy and 2 more countries
Women only
A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →
Of the 45 Fabry Disease studies recruiting now, 32 (71%) set no upper age limit and 11 (24%) stop at 75 or younger; 20 take children under 18; 7 take healthy volunteers.
This study: 16 Years to 50 Years · male · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
94 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 11 · Phase 2 23 · Phase 3 22 · Phase 4 7
First in 1995; this study’s year is marked. 7 started in 2018.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 15 is below the median of 22 across 108 interventional studies indexed under Fabry Disease.
Median enrollment 22 across the 58 interventional studies, 54 across the 34 observational. Of the 66 that completed or were terminated, 37 (56%) have results posted.
This tab as a report to print or save as PDF → With an account.
60 of 94 have an industry lead sponsor. The 10 most frequent:
AVROBIO is the lead sponsor of 5 studies on the registry; none are open to participants now.
AVROBIO has 2 studies filed under Fabry Disease — fewer than ten, so there is no comparison to draw.
1 of the studies in Fabry Disease with a site in United States that are under way reach primary completion within a year, 1 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT04020055Phase 3Amicus TherapeuticsA Study to Evaluate Migalastat in Fabry Subjects With Amenable GLA Variant and Renal Disease | 2026-12-31 |
Add it to your calendar (.ics) → With an account.
Among the 94 studies in Fabry Disease with a site in United States, from their registry updates:
This tab as a report to print or save as PDF → With an account.
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.
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Subject had a history of 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].
Other inclusion/exclusion criteria apply.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: AVR-RD-01
Single IV infusion of between 3 - 20 x 10\^6 CD34+ cells/kg.
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline to Week 48 post gene therapy
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.
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)
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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)
mGFR is a measure of the time the kidney takes to filter products that the body does not naturally produce.
Time frame: 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.
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
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.
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)
LVMI is a surrogate of left ventricular hypertrophy. An increase in LVMI is an independent risk factor for cardiovascular morbidity and mortality.
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)
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.
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
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.
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
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.
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)
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.
Time frame: At Week 48 post gene therapy
Total number of subjects who signed the ICF was 16 (one subject who re-screened was not considered enrolled initially), as a result there were 15 distinct subjects who signed ICF. There were 4 participants who failed screening and were not rescreened. The Safety population consists of all 11 enrolled subjects who received any preparatory medication. The Infused population consists of all 9 enrolled subjects who received all preparatory medications and AVR-RD-01.
| Milestone | Single Assignment AVR-RD-01 |
|---|---|
| Started | 15 |
| Safety population | 11 |
| Infused population | 9 |
| Completed | 6 |
| Not completed | 9 |
| Withdrew: Study terminated by the sponsor | 5 |
| Withdrew: Did not pass screening | 4 |
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.
| Number of events | Single Assignment AVR-RD-01 |
|---|---|
| AE | 354 |
| SAE | 13 |
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.
| Number of positive subjects | Single Assignment AVR-RD-01 |
|---|---|
| Change From Baseline in Immunogenicity of AVR-RD-01 | 4 |
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.
| Number of positive subjects | Single Assignment AVR-RD-01 |
|---|---|
| Presence of Replication Competent Lentivirus (RCL) | 0 |
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.
| number of abnormal clonal proliferations | Single Assignment AVR-RD-01 |
|---|---|
| Evaluation of Aberrant Clonal Expansion | 0 |
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.
| Number of inclusions | Single Assignment AVR-RD-01 |
|---|---|
| Change From Baseline in the Average Number of Gb3 Inclusions (ie, Myelinosomes) Per Kidney Peritubular Capillary (PTC) Per Subject | -3.555 (-4.020 to -3.090) |
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.
| copies/diploid genome | Single Assignment AVR-RD-01 |
|---|---|
| Week 24 | 0.383 ± 0.4628 |
| Week 48 | 0.313 ± 0.3447 |
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.
| nmol/h/mg | Single Assignment AVR-RD-01 |
|---|---|
| CFB Plasma W24 | 1.973 ± 2.585 |
| CFB Plasma W48 | 1.548 ± 2.152 |
| CFB PBL Week 24 | 29.524 ± 39.194 |
| CFB PBL Week 48 | 18.973 ± 32.800 |
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.
| nM | Single Assignment AVR-RD-01 |
|---|---|
| Week 24 | -3334.0 ± 3846.8 |
| Week 48 | -5067.8 ± 4067.0 |
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.
| nmol/mmol creatinine | Single Assignment AVR-RD-01 |
|---|---|
| Week 24 | -11.73 ± 309.78 |
| Week 48 | -188.73 ± 262.90 |
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.
| number of myelinosomes | Single Assignment AVR-RD-01 |
|---|---|
| Myelinosomes in superficial dermal capillary endothelial cells (Week 24) | -0.4 ± 1.3 |
| Myelinosomes in superficial dermal capillary endothelial cells (Week 48) | -0.5 ± 1.0 |
| Myelinosomes in deep dermal capillary endothelial cells (Week 24) | 0 ± 1.3 |
| Myelinosomes in deep dermal capillary endothelial cells (Week 48) | -0.5 ± 1.0 |
| Myelinosomes in vascular smooth muscle cells (Week 24) | 0.1 ± 1.2 |
| Myelinosomes in vascular smooth muscle cells (Week 48) | -0.5 ± 1.0 |
| Myelinosomes in perineurium (Week 24) | 0 ± 1.4 |
| Myelinosomes in perineurium (Week 48) | -0.5 ± 1.0 |
mGFR is a measure of the time the kidney takes to filter products that the body does not naturally produce.
| mL/min/1.73m^2 | Single Assignment AVR-RD-01 |
|---|---|
| Change From Baseline in Renal Function as Assessed by Measured Glomerular Filtration Rate (mGFR) | -2.358 ± 14.502 |
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.
| mL/min/1.73 m^2 | Single Assignment AVR-RD-01 |
|---|---|
| Week 24 | -6.386 ± 9.699 |
| Week 48 | -3.561 ± 7.332 |
No measurements were reported for this outcome.
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.
| mg/dL | Single Assignment AVR-RD-01 |
|---|---|
| Week 24 | 0.915 ± 6.704 |
| Week 48 | 0.643 ± 5.789 |
LVMI is a surrogate of left ventricular hypertrophy. An increase in LVMI is an independent risk factor for cardiovascular morbidity and mortality.
| g/m^2 | Single Assignment AVR-RD-01 |
|---|---|
| Change From Baseline in Left Ventricular Mass Index (LVMI) as Assessed by Cardiac Magnetic Resonance Imaging (MRI) | 7.270 ± 6.055 |
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.
| units on a scale | Single Assignment AVR-RD-01 |
|---|---|
| Abdominal Pain Week 24 | -0.445 ± 0.583 |
| Abdominal Pain Week 48 | -0.497 ± 0.626 |
| Stool Consistency Week 24 | -0.373 ± 0.216 |
| Stool Consistency Week 48 | -0.530 ± 0.104 |
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.
| score on a scale | Single Assignment AVR-RD-01 |
|---|---|
| Week 24 (pain severity) | -0.188 ± 0.874 |
| Week 48 (pain severity) | -0.500 ± 0.612 |
| Week 24 (pain interference) | 0.073 ± 1.007 |
| Week 48 (pain interference) | -0.573 ± 0.996 |
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.
| score on a scale | Single Assignment AVR-RD-01 |
|---|---|
| Physical Functioning Week 48 | 3.235 ± 4.810 |
| Mental Functioning Week 48 | -1.580 ± 4.652 |
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.
| copies/diploid genome | Single Assignment AVR-RD-01 |
|---|---|
| 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) | 1.14 (1.14 to 1.14) |
Collected over Up to week 48. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Single Assignment AVR-RD-01 | 0/11 (0%) | 8/11 (72.7%) | 11/11 (100%) |
| Event | Single Assignment AVR-RD-01 |
|---|---|
| Febrile neutropeniaBlood and lymphatic system disorders | 2/11 |
| ThrombocytopeniaBlood and lymphatic system disorders | 1/11 |
| NauseaGastrointestinal disorders | 1/11 |
| OdynophagiaGastrointestinal disorders | 1/11 |
| VomitingGastrointestinal disorders | 1/11 |
| Mucosal inflammationGeneral disorders | 1/11 |
| PyrexiaGeneral disorders | 1/11 |
| CholelithiasisHepatobiliary disorders | 1/11 |
| DehydrationMetabolism and nutrition disorders | 1/11 |
| SeizureNervous system disorders | 1/11 |
| Event | Single Assignment AVR-RD-01 |
|---|---|
| NauseaGastrointestinal disorders | 10/11 |
| LeukopeniaBlood and lymphatic system disorders | 9/11 |
| NeutropeniaBlood and lymphatic system disorders | 9/11 |
| ThrombocytopeniaBlood and lymphatic system disorders | 9/11 |
| Febrile neutropeniaBlood and lymphatic system disorders | 8/11 |
| DiarrhoeaGastrointestinal disorders | 8/11 |
| HeadacheNervous system disorders | 8/11 |
| AlopeciaSkin and subcutaneous tissue disorders | 8/11 |
| VomitingGastrointestinal disorders | 6/11 |
| Citrate toxicityInjury, poisoning and procedural complications | 6/11 |
Safety population consists of all enrolled subjects who received any preparatory medication.
| Age, Continuous(years) | Single Assignment AVR-RD-01 |
|---|---|
| Mean | 31.45 ± 10.98 |
| Sex: Female, Male(Participants) | Single Assignment AVR-RD-01 |
|---|---|
| Female | 0 |
| Male | 11 |
| Ethnicity (NIH/OMB)(Participants) | Single Assignment AVR-RD-01 |
|---|---|
| Hispanic or Latino | 5 |
| Not Hispanic or Latino | 6 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Single Assignment AVR-RD-01 |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 8 |
| More than one race | 0 |
| Unknown or Not Reported | 2 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Feb 2018 to primary completion in Mar 2022, 48 months.
Results were first posted in Jan 2024, 1 year 9 months after primary completion. A results delay was requested in Nov 2022.
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