Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Chiesi Farmaceutici S.p.A. | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is the first human treatment with PRX-102, an enzyme being developed as a long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry disease (alpha galactosidase deficiency). The safety, tolerability, and exploratory efficacy will be evaluated in this study of increasing doses. Patients will be treated with infusions every two weeks for 12 months.
Under the PB-102-F01 study protocol, patients will be enrolled into one of three PRX-102 dosing groups (0.2 mg/kg, 1.0 mg/kg, 2.0 mg/kg) and receive PRX-102 as an intravenous infusion every 2 weeks for 12 weeks (3 months). Patients who finish the PB-102-F01 study will be enrolled in the PB-102-F02 extension study and receive the same dose they had received in the PB-102-F01 study for an additional 38 weeks (9 months).
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 0.2 mg/kg | Experimental | PRX-102 0.2 mg/kg every 2 weeks |
|
| 1 mg/kg | Experimental | PRX-102 1 mg/kg every 2 weeks |
|
| 2 mg/kg | Experimental | PRX-102 2 mg/kg every 2 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PRX-102 | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events | Reportings of adverse events reported by the patient and from monitoring with clinical laboratory, physical examination and ECG. Results represent the number of AEs that were considered possibly, probably, or definitely related to treatment. | 12 months |
Not provided
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Gb3 Concentrations | Results are presented as mean percent change from baseline (visit 1) to 12 months +/- standard error. | Plasma Gb3 concentration (ug/mL) was measured at baseline and every 3 months up to 12 months. |
| Kidney Function - Change in eGFR |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC Davis Medical Center, MIND Institute Department of Pediatrics, Section of Genetics | Sacramento | California | 95817 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30834538 | Result | Schiffmann R, Goker-Alpan O, Holida M, Giraldo P, Barisoni L, Colvin RB, Jennette CJ, Maegawa G, Boyadjiev SA, Gonzalez D, Nicholls K, Tuffaha A, Atta MG, Rup B, Charney MR, Paz A, Szlaifer M, Alon S, Brill-Almon E, Chertkoff R, Hughes D. Pegunigalsidase alfa, a novel PEGylated enzyme replacement therapy for Fabry disease, provides sustained plasma concentrations and favorable pharmacodynamics: A 1-year Phase 1/2 clinical trial. J Inherit Metab Dis. 2019 May;42(3):534-544. doi: 10.1002/jimd.12080. Epub 2019 Apr 8. |
Not provided
Not provided
Eighteen (18) patients were eligible for enrollment for PB-102-F01 study. The eligible patients who completed PB-102-F01, needed to sign an informed consent for PB-102-F02.
Recruitment efforts were conducted in North and South America, Europe and Australia for PB-102-F01 (3 months), and all patients who completed this study continued to the PB-102-F02 extension study for an additional 9 months, to complete a total of 12 months of treatment. 18 patients were eligible for enrollment, and 16 completed the study.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 0.2 mg/kg | PRX-102 0.2 mg/kg every 2 weeks PRX-102 |
| FG001 | 1 mg/kg | PRX-102 1 mg/kg every 2 weeks PRX-102 |
| FG002 | 2 mg/kg | PRX-102 2 mg/kg every 2 weeks PRX-102 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PB-102-F01 |
|
| |||||||||||||||||||||
| PB-102-F02 |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 0.2 mg/kg | PRX-102 0.2 mg/kg every 2 weeks PRX-102 |
| BG001 | 1 mg/kg | PRX-102 1 mg/kg every 2 weeks PRX-102 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Adverse Events | Reportings of adverse events reported by the patient and from monitoring with clinical laboratory, physical examination and ECG. Results represent the number of AEs that were considered possibly, probably, or definitely related to treatment. | Posted | Number | adverse events | 12 months |
|
AEs were collected from the start of treatment throughout the 12 months of the study, plus a follow-up visit 2 months after 12-months study visit.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 0.2 mg/kg | PRX-102 0.2 mg/kg every 2 weeks | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Renal Hematoma | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment | One patient in the 1mg/kg group experienced a renal hematoma due to the kidney biopsy at baseline. The patient was treated and the renal hematoma was resolved. This event was considered unrelated to treatment. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | Vascular disorders | MedDRA (16.1) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Raul Chertkoff | Protalix Ltd | +972-4-9028100 | raul@protalix.com |
Not provided
| ID | Term |
|---|---|
| D000795 | Fabry Disease |
| ID | Term |
|---|---|
| D013106 | Sphingolipidoses |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Estimated glomerular filtration rate (eGFR) was calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Levels of eGFR calculated by the CKD-EPI equation, based on measured serum creatinine on day 1, weeks 4, 8, 12, 26, 38 and 52 are used to determine the annualized slope of eGFR per patient over a 12 months period. The absolute mean change from baseline (visit 1) to 12 months is then derived from the eGFR slope.
| eGFR is performed at baseline (day 1) weeks 4, 8, 12, 26, 38 and 52 (12 months) |
| Plasma Lyso-Gb3 Levels | Results are presented as mean percent change from baseline (visit 1) to 12 months +/- standard error. | Plasma Lyso-Gb3 concentration (ng/mL) was measured at baseline and every 3 months up to 12 months. |
| Change in Kidney Gb3 Accumulation | Kidney biopsy was performed at baseline of study PB-102-F01 and following 6 months treatment with PRX-102. Approximately 300 capillaries were scored in each specimen. A quantitative Barisoni Lipid Inclusion Scoring System (BLISS) was used for scoring Gb3 inclusions in kidney peritubular capillary (PTC) biopsy samples.The scoring system was implemented by 3 blinded pathologists/readers.The BLISS scoring methodology consists of counting the number of Gb-3 inclusions per capillary previously annotated.The final score of each biopsy was the average number of inclusions per capillary. A decrease in scoring from baseline to 6 Month is considered an indication for clinical improvement. | Visit 1 (day 1) in PB-102-F01 study and after a total of 6 months of treatment (i.e., at 3 months into study PB-102-F02). |
| Cardiac Fibrosis Per MRI | Cardiac MRI was performed to estimate the percentage and mass of the myocardial fibrotic area. Results represent the number of subjects with fibrosis after 1 year of treatment. | Cardiac MRI was performed in order to assess myocardial fibrosis at baseline, 6 months and 12 months visit. |
| Cardiac MRI - Ejection Fraction | Results are presented as mean percent change from baseline (visit 1) to 12 months. | Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months. |
| Cardiac MRI - LVM | Results are presented as mean percent change from baseline (visit 1) to 12 months. | Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months. |
| Cardiac MRI - LVMI | Cardiac MRI with computer-calculated left ventricular mass index were conducted at baseline, 6 month, and 12 months. Results are presented as mean percent change from baseline (visit 1) to 12 months. LVMI is calculated by dividing the left ventricular mass by body surface area. | Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months. |
| Pharmacokinetics - AUC | PK parameters were derived from the plasma concentration versus time profiles. Results reported represent the averaged values following a single dosing of the study drug. | PK parameters were determined on Day 1 and 3, 6, and 12 months at these time points: pre-infusion (baseline); 1 h after the beginning of the infusion; at the end of the infusion; 1, 4, 8, 24, 48±3, 72±3, 96±3 h and 2 weeks ± 3 days post-infusion. |
| Pharmacokinetics - Terminal Half Life | PK parameters were derived from the plasma concentration versus time profiles. Results reported represent the averaged values following a single dosing of the study drug. | PK parameters were determined on Day 1 and 3, 6, and 12 months at these time points: pre-infusion (baseline); 1 h after the beginning of the infusion; at the end of the infusion; 1, 4, 8, 24, 48±3, 72±3, 96±3 h and 2 weeks ± 3 days post-infusion. |
| Pharmacokinetics - Clearance of Drug (Cl) | PK parameters were derived from the plasma concentration versus time profiles. Clearance of drug from plasma represents the volume of plasma cleared of the drug per unit time per Kg. Results reported represent the averaged values following a single dosing of the study drug. | PK parameters were determined on Day 1 and 3, 6, and 12 months at these time points: pre-infusion (baseline); 1 h after the beginning of the infusion; at the end of the infusion; 1, 4, 8, 24, 48±3, 72±3, 96±3 h and 2 weeks ± 3 days post-infusion. |
| Pharmacokinetics - Volume of Distribution (Vz) | PK parameters were derived from the plasma concentration versus time profiles. Vz is the volume of distribution during the elimination phase. Results reported represent the averaged values following a single dosing of the study drug. | PK parameters were determined on Day 1 and 3, 6, and 12 months at these time points: pre-infusion (baseline); 1 h after the beginning of the infusion; at the end of the infusion; 1, 4, 8, 24, 48±3, 72±3, 96±3 h and 2 weeks ± 3 days post-infusion. |
| Pharmacokinetics - Cmax | Pharmacokinetic (PK) parameters were derived from the plasma concentration versus time profiles. Cmax is the maximal plasma concentration of a drug after administration. Results reported represent the averaged values following a single dosing of the study drug. | PK parameters were determined on Day 1 and 3, 6, and 12 months at these time points: pre-infusion (baseline); 1 h after the beginning of the infusion; at the end of the infusion; 1, 4, 8, 24, 48±3, 72±3, 96±3 h and 2 weeks ± 3 days post-infusion. |
| Number of Participants With Anti-Drug Antibodies | Results reported represent the number of participants who were tested positive for anti-pegunigalsidase alfa (PRX-102) antibodies, including neutralizing antibodies in patients having a positive IgG antibody response per group, at Visit 1, 2 (Month 1), and then every 2 months during the study, and 2 months after the last infusion. | Anti-pegunigalsidase alfa (PRX-102) antibodies, including neutralizing antibodies in patients having a positive IgG antibody response, were assessed at Visit 1, 2 (Month 1), and then every 2 months during the study, and 2 months after the last infusion. |
| Change in Short Form Brief Pain Inventory (BPI) | Pain severity (worst, least, average, and right now) is summarized at baseline, 3-month, 6-month and 12-month of the study. The Short Form Brief Pain Inventory (BPI) is based on a 10-point scale, where 0=no pain and 10=pain as bad as you can imagine. A reduction in pain severity score indicated an improvement. The changes from baseline for individual scores and composite scores (a mean severity score) was assessed. The mean change in score from baseline at the 12-month visit is reflected. | The Short Form Brief Pain Inventory (BPI) is assessed at baseline, 3-month, 6-month, and 12-month visits. |
| Urine Creatinine Level | Proteinuria is assessed using spot urine tests at baseline, 3-month, 6-month, 9-month, and 12-month visits. The percent changes of urine creatinine level at the 12-month visit from baseline is reflected. | Urine creatinine level is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits using spot urine tests. |
| Urine Protein/Creatinine Ratio | Proteinuria is assessed using spot urine tests at baseline, 3-month, 6-month, 9-month, and 12-month visits. The percent changes of urine protein/creatinine ratio at the 12-month visit from baseline is reflected. | Protein/.creatinine ratio is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits |
| Total Urine Protein Level | Proteinuria is assessed using spot urine tests at baseline, 3-month, 6-month, 9-month, and 12-month visits. The percent changes of total urine protein level at the 12-month visit from baseline is reflected. | Total urine protein level is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits. |
| Brain MRI | Qualitative assessments regarding evidence of stroke using brain MRI were summarized at baseline and 12-month visits. Number is subjects with evidence of stoke on the brain MRI at the 12-month visit is reflected. | Brain MRI is performed at baseline and 12-month visit. |
| Change in Mainz Severity Score Index (MSSI) | The Mainz Severity Score Index (MSSI) is useful for monitoring clinical improvement in patients receiving enzyme replacement therapy. The MSSI scoring system is composed of four sections that cover the general, neurological,cardiovascular and renal signs and symptoms of Fabry disease. Each section includes a group of signs and symptoms that are associated with Fabry disease. The minimal score is 0, and the maximum score for the general section is 18. A higher score indicates more severe clinical manifestations of the disease.The MSSI is performed at baseline, 6-month, and 12-month. The overall mean reduction of the total general score at 12-month from baseline is reflected. | The MSSI is performed at baseline, 6-month, and 12-month |
| Gastrointestinal Symptoms Questionnaire - Severity of Abdominal Pain | A qualitative assessments regarding abdominal pain and diarrhea at baseline, 3-month, 6-month, 9-month, and 12-month visits. The subjects were asked to report the severity of their abdominal pain as no pain, mild, moderate, severe or really severe. The number of subjects who reported no or mild abdominal pain at the 12-month visit are reflected. | The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits. |
| Gastrointestinal Symptoms Questionnaire - Frequency of Abdominal Pain | A qualitative assessments regarding abdominal pain and diarrhea at baseline, 3-month, 6-month, 9-month, and 12-month visits. The subjects were asked to report their frequency of abdominal pain as never, rarely, monthly, weekly, or daily. The numbers of subjects who reported never or rarely having abdominal pain at the 12-month visit are reflected. | The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits. |
| Gastrointestinal Symptoms Questionnaire - Frequency of Diarrhea | A qualitative assessments regarding abdominal pain and diarrhea at baseline, 3-month, 6-month, 9-month, and 12-month visits. The subjects were asked to report their frequency of diarrhea as never, rarely, monthly, weekly, or daily. The number of subjects who reported never or rarely having diarrhea at the 12-month visit is reflected. | The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits. |
| Department of Human Genetics, Emory University School of Medicine |
| Atlanta |
| Georgia |
| 30322 |
| United States |
| University of Iowa Health Clinics | Iowa City | Iowa | 52242 | United States |
| University of Kansas Medical Center | Kansas City | Kansas | 66160 | United States |
| Johns Hopkins University School of Medicine | Baltimore | Maryland | 21205 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania | 15224 | United States |
| Research Baylor Institute of Metabolic Disease | Dallas | Texas | 75226 | United States |
| O & O Alpan LLC | Fairfax | Virginia | 22030 | United States |
| Royal Melbourne Hospital | Victoria Park | 3050 | Australia |
| Hematology and Clinical Research Private Institute | Asunción | Paraguay |
| Clinical Center of Serbia | Belgrade | Serbia |
| Hospital de Dia Quiron Zaragoza | Zaragoza | 50012 | Spain |
| The Royal Free Hospital | London | NW3 2QG | United Kingdom |
| NOT COMPLETED |
|
| BG002 |
| 2 mg/kg |
PRX-102 2 mg/kg every 2 weeks PRX-102 |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Phenotypically Classic vs Non Classic Fabry Patients | A subgroup analysis of patients with phenotypically classic Fabry disease was conducted only in the efficacy group. The efficacy group includes those who completed the study. | Count of Participants | Participants |
|
| 1.0 mg/kg |
PRX-102 1.0 mg/kg every 2 weeks |
| OG003 | 2.0 mg/kg | PRX-102 2.0 mg/kg every 2 weeks |
|
|
| Other Pre-specified | Plasma Gb3 Concentrations | Results are presented as mean percent change from baseline (visit 1) to 12 months +/- standard error. | Posted | Mean | Standard Error | mean percent change | Plasma Gb3 concentration (ug/mL) was measured at baseline and every 3 months up to 12 months. |
|
|
|
| Other Pre-specified | Kidney Function - Change in eGFR | Estimated glomerular filtration rate (eGFR) was calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Levels of eGFR calculated by the CKD-EPI equation, based on measured serum creatinine on day 1, weeks 4, 8, 12, 26, 38 and 52 are used to determine the annualized slope of eGFR per patient over a 12 months period. The absolute mean change from baseline (visit 1) to 12 months is then derived from the eGFR slope. | Posted | Mean | Standard Error | mL/min/1.73 m2 | eGFR is performed at baseline (day 1) weeks 4, 8, 12, 26, 38 and 52 (12 months) |
|
|
|
| Other Pre-specified | Plasma Lyso-Gb3 Levels | Results are presented as mean percent change from baseline (visit 1) to 12 months +/- standard error. | Posted | Mean | Standard Error | mean percent change | Plasma Lyso-Gb3 concentration (ng/mL) was measured at baseline and every 3 months up to 12 months. |
|
|
|
| Other Pre-specified | Change in Kidney Gb3 Accumulation | Kidney biopsy was performed at baseline of study PB-102-F01 and following 6 months treatment with PRX-102. Approximately 300 capillaries were scored in each specimen. A quantitative Barisoni Lipid Inclusion Scoring System (BLISS) was used for scoring Gb3 inclusions in kidney peritubular capillary (PTC) biopsy samples.The scoring system was implemented by 3 blinded pathologists/readers.The BLISS scoring methodology consists of counting the number of Gb-3 inclusions per capillary previously annotated.The final score of each biopsy was the average number of inclusions per capillary. A decrease in scoring from baseline to 6 Month is considered an indication for clinical improvement. | 3 patients were not included in the renal biopsies Gb3 analysis. 1 male patient's biopsies were mixed up by the lab; 1 female patient's baseline biopsy didn't include cortex tissue making sample unreadable; and 1 male patient carries a cardiac GLA variant (p.N215S) associated with rare renal manifestation and had a low BLISS baseline score | Posted | Mean | Standard Error | Percent change | Visit 1 (day 1) in PB-102-F01 study and after a total of 6 months of treatment (i.e., at 3 months into study PB-102-F02). |
|
|
|
| Other Pre-specified | Cardiac Fibrosis Per MRI | Cardiac MRI was performed to estimate the percentage and mass of the myocardial fibrotic area. Results represent the number of subjects with fibrosis after 1 year of treatment. | Posted | Number | number of subjects | Cardiac MRI was performed in order to assess myocardial fibrosis at baseline, 6 months and 12 months visit. |
|
|
|
| Other Pre-specified | Cardiac MRI - Ejection Fraction | Results are presented as mean percent change from baseline (visit 1) to 12 months. | Posted | Mean | Standard Error | Percent Change | Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months. |
|
|
|
| Other Pre-specified | Cardiac MRI - LVM | Results are presented as mean percent change from baseline (visit 1) to 12 months. | Posted | Mean | Standard Error | Percent change | Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months. |
|
|
|
| Other Pre-specified | Cardiac MRI - LVMI | Cardiac MRI with computer-calculated left ventricular mass index were conducted at baseline, 6 month, and 12 months. Results are presented as mean percent change from baseline (visit 1) to 12 months. LVMI is calculated by dividing the left ventricular mass by body surface area. | Posted | Mean | Standard Error | Percent Change | Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months. |
|
|
|
| Other Pre-specified | Pharmacokinetics - AUC | PK parameters were derived from the plasma concentration versus time profiles. Results reported represent the averaged values following a single dosing of the study drug. | Posted | Mean | Standard Error | ng*hr/ml | PK parameters were determined on Day 1 and 3, 6, and 12 months at these time points: pre-infusion (baseline); 1 h after the beginning of the infusion; at the end of the infusion; 1, 4, 8, 24, 48±3, 72±3, 96±3 h and 2 weeks ± 3 days post-infusion. |
|
|
|
| Other Pre-specified | Pharmacokinetics - Terminal Half Life | PK parameters were derived from the plasma concentration versus time profiles. Results reported represent the averaged values following a single dosing of the study drug. | Posted | Mean | Standard Error | hour | PK parameters were determined on Day 1 and 3, 6, and 12 months at these time points: pre-infusion (baseline); 1 h after the beginning of the infusion; at the end of the infusion; 1, 4, 8, 24, 48±3, 72±3, 96±3 h and 2 weeks ± 3 days post-infusion. |
|
|
|
| Other Pre-specified | Pharmacokinetics - Clearance of Drug (Cl) | PK parameters were derived from the plasma concentration versus time profiles. Clearance of drug from plasma represents the volume of plasma cleared of the drug per unit time per Kg. Results reported represent the averaged values following a single dosing of the study drug. | Posted | Mean | Standard Error | ml/hr/kg | PK parameters were determined on Day 1 and 3, 6, and 12 months at these time points: pre-infusion (baseline); 1 h after the beginning of the infusion; at the end of the infusion; 1, 4, 8, 24, 48±3, 72±3, 96±3 h and 2 weeks ± 3 days post-infusion. |
|
|
|
| Other Pre-specified | Pharmacokinetics - Volume of Distribution (Vz) | PK parameters were derived from the plasma concentration versus time profiles. Vz is the volume of distribution during the elimination phase. Results reported represent the averaged values following a single dosing of the study drug. | Posted | Mean | Standard Error | ml/kg | PK parameters were determined on Day 1 and 3, 6, and 12 months at these time points: pre-infusion (baseline); 1 h after the beginning of the infusion; at the end of the infusion; 1, 4, 8, 24, 48±3, 72±3, 96±3 h and 2 weeks ± 3 days post-infusion. |
|
|
|
| Other Pre-specified | Pharmacokinetics - Cmax | Pharmacokinetic (PK) parameters were derived from the plasma concentration versus time profiles. Cmax is the maximal plasma concentration of a drug after administration. Results reported represent the averaged values following a single dosing of the study drug. | Posted | Mean | Standard Error | ng/ml | PK parameters were determined on Day 1 and 3, 6, and 12 months at these time points: pre-infusion (baseline); 1 h after the beginning of the infusion; at the end of the infusion; 1, 4, 8, 24, 48±3, 72±3, 96±3 h and 2 weeks ± 3 days post-infusion. |
|
|
|
| Other Pre-specified | Number of Participants With Anti-Drug Antibodies | Results reported represent the number of participants who were tested positive for anti-pegunigalsidase alfa (PRX-102) antibodies, including neutralizing antibodies in patients having a positive IgG antibody response per group, at Visit 1, 2 (Month 1), and then every 2 months during the study, and 2 months after the last infusion. | Posted | Number | participants | Anti-pegunigalsidase alfa (PRX-102) antibodies, including neutralizing antibodies in patients having a positive IgG antibody response, were assessed at Visit 1, 2 (Month 1), and then every 2 months during the study, and 2 months after the last infusion. |
|
|
|
| Other Pre-specified | Change in Short Form Brief Pain Inventory (BPI) | Pain severity (worst, least, average, and right now) is summarized at baseline, 3-month, 6-month and 12-month of the study. The Short Form Brief Pain Inventory (BPI) is based on a 10-point scale, where 0=no pain and 10=pain as bad as you can imagine. A reduction in pain severity score indicated an improvement. The changes from baseline for individual scores and composite scores (a mean severity score) was assessed. The mean change in score from baseline at the 12-month visit is reflected. | Posted | Mean | Standard Error | score on a scale | The Short Form Brief Pain Inventory (BPI) is assessed at baseline, 3-month, 6-month, and 12-month visits. |
|
|
|
| Other Pre-specified | Urine Creatinine Level | Proteinuria is assessed using spot urine tests at baseline, 3-month, 6-month, 9-month, and 12-month visits. The percent changes of urine creatinine level at the 12-month visit from baseline is reflected. | Posted | Mean | Standard Error | Percentage change from baseline | Urine creatinine level is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits using spot urine tests. |
|
|
|
| Other Pre-specified | Urine Protein/Creatinine Ratio | Proteinuria is assessed using spot urine tests at baseline, 3-month, 6-month, 9-month, and 12-month visits. The percent changes of urine protein/creatinine ratio at the 12-month visit from baseline is reflected. | Posted | Mean | Standard Error | Percentage change from baseline | Protein/.creatinine ratio is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits |
|
|
|
| Other Pre-specified | Total Urine Protein Level | Proteinuria is assessed using spot urine tests at baseline, 3-month, 6-month, 9-month, and 12-month visits. The percent changes of total urine protein level at the 12-month visit from baseline is reflected. | Posted | Mean | Standard Error | Percentage change from baseline | Total urine protein level is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits. |
|
|
|
| Other Pre-specified | Brain MRI | Qualitative assessments regarding evidence of stroke using brain MRI were summarized at baseline and 12-month visits. Number is subjects with evidence of stoke on the brain MRI at the 12-month visit is reflected. | Posted | Count of Participants | Participants | Brain MRI is performed at baseline and 12-month visit. |
|
|
|
| Other Pre-specified | Change in Mainz Severity Score Index (MSSI) | The Mainz Severity Score Index (MSSI) is useful for monitoring clinical improvement in patients receiving enzyme replacement therapy. The MSSI scoring system is composed of four sections that cover the general, neurological,cardiovascular and renal signs and symptoms of Fabry disease. Each section includes a group of signs and symptoms that are associated with Fabry disease. The minimal score is 0, and the maximum score for the general section is 18. A higher score indicates more severe clinical manifestations of the disease.The MSSI is performed at baseline, 6-month, and 12-month. The overall mean reduction of the total general score at 12-month from baseline is reflected. | Posted | Mean | Standard Error | score of a scale | The MSSI is performed at baseline, 6-month, and 12-month |
|
|
|
| Other Pre-specified | Gastrointestinal Symptoms Questionnaire - Severity of Abdominal Pain | A qualitative assessments regarding abdominal pain and diarrhea at baseline, 3-month, 6-month, 9-month, and 12-month visits. The subjects were asked to report the severity of their abdominal pain as no pain, mild, moderate, severe or really severe. The number of subjects who reported no or mild abdominal pain at the 12-month visit are reflected. | Posted | Number | participants | The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits. |
|
|
|
| Other Pre-specified | Gastrointestinal Symptoms Questionnaire - Frequency of Abdominal Pain | A qualitative assessments regarding abdominal pain and diarrhea at baseline, 3-month, 6-month, 9-month, and 12-month visits. The subjects were asked to report their frequency of abdominal pain as never, rarely, monthly, weekly, or daily. The numbers of subjects who reported never or rarely having abdominal pain at the 12-month visit are reflected. | Posted | Count of Participants | Participants | The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits. |
|
|
|
| Other Pre-specified | Gastrointestinal Symptoms Questionnaire - Frequency of Diarrhea | A qualitative assessments regarding abdominal pain and diarrhea at baseline, 3-month, 6-month, 9-month, and 12-month visits. The subjects were asked to report their frequency of diarrhea as never, rarely, monthly, weekly, or daily. The number of subjects who reported never or rarely having diarrhea at the 12-month visit is reflected. | Posted | Count of Participants | Participants | The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits. |
|
|
|
| 6 |
| 0 |
| 6 |
| 2 |
| 6 |
| EG001 | 1 mg/kg | PRX-102 1.0 mg/kg every 2 weeks | 0 | 8 | 1 | 8 | 7 | 8 |
| EG002 | 2 mg/kg | PRX-102 2.0 mg/kg every 2 weeks | 0 | 4 | 1 | 4 | 2 | 4 |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment | A 52 y.o. male experienced a bronchospasm related to the study drug 40 minutes following the first infusion initiation, was treated, recovered, and discontinued Per Protocol. Anti PRX-102 IgG was negative and anti PRX-102 IgE was positive at baseline |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Chest pain | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Infusion reaction | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Itching | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Sweating | Skin and subcutaneous tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Corneal Edema | Eye disorders | MedDRA (16.1) | Systematic Assessment |
|
| Conjunctival Hemorrhage | Eye disorders | MedDRA (16.1) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Edema | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Peripheral Edema | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Paranasal sinus hypersecretion | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
|
| Visual field defect | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
|
| Typical aura without headache | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA (16.1) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (16.1) | Systematic Assessment |
|
| Musculoskeletal Stiffness | Musculoskeletal and connective tissue disorders | MedDRA (16.1) | Systematic Assessment |
|
| Nervousness | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
|
Not provided
Not provided
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D059345 | Cerebral Small Vessel Diseases |
| D002561 | Cerebrovascular Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008661 | Metabolism, Inborn Errors |
| D008064 | Lipidoses |
| D008052 | Lipid Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D052439 | Lipid Metabolism Disorders |
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Non Classic Fabry Patients |
|