Fabry Disease
Conditions
Keywords
Fabry disease, Alpha galactosidase deficiency, Metabolic storage disease
Brief summary
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.
Detailed description
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).
Interventions
DRUGPRX-102
Sponsors
Chiesi Farmaceutici S.p.A.
Protalix
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Symptomatic adult Fabry patients (≥18 yrs) * Males: plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than lower limit of normal (LLN in plasma=3.2 nmol/hr/ml, LLN in leucocytes=32 nmol/hr/mg/protein) * Females: historical genetic test results consistent with Fabry mutations * Globotriaosylceramide (Gb3) concentration in urine \> 1.5 times upper normal limit * Patients who have never received enzyme replacement therapy (ERT) in the past, or patients who have not received ERT in the past 6 months and have a negative anti alpha galactosidase antibody test * eGFR ≥ 60 mL/min/1.73m2 * The patient signs informed consent * Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically acceptable method of contraception, not including the rhythm method
Exclusion criteria
* Participation in any trial of an investigational drug within 30 days prior to study screening * Chronic kidney disease stages 3-5 (CKD 3-5) (Appendix 7) * History of dialysis or renal transplantation * Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening * Severe myocardial fibrosis by MRI (≥2 late-enhancement \[LE\] positive left ventricular segments) (Weidemann et al. 2009) * History of clinical stroke * Pregnant or nursing * Presence of HIV and/or HBsAg and/or Hepatitis C infections * Known allergies to ERT * Known allergy to Gadolinium based contrast agents * Presence of any medical, emotional, behavioral or psychological condition that, in the judgment of the Investigator and/or Medical Director, would interfere with the patient's compliance with the requirements of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 12 months | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Kidney Function - Change in eGFR | eGFR is performed at baseline (day 1) weeks 4, 8, 12, 26, 38 and 52 (12 months) | 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. |
| Plasma Lyso-Gb3 Levels | Plasma Lyso-Gb3 concentration (ng/mL) was measured at baseline and every 3 months up to 12 months. | Results are presented as mean percent change from baseline (visit 1) to 12 months +/- standard error. |
| Change in Kidney Gb3 Accumulation | 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). | 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. |
| Cardiac Fibrosis Per MRI | Cardiac MRI was performed in order to assess myocardial fibrosis at baseline, 6 months and 12 months visit. | 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 - Ejection Fraction | Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months. | Results are presented as mean percent change from baseline (visit 1) to 12 months. |
| Cardiac MRI - LVM | Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months. | Results are presented as mean percent change from baseline (visit 1) to 12 months. |
| Cardiac MRI - LVMI | Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months. | 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. |
| Pharmacokinetics - AUC | 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. | 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. |
| Pharmacokinetics - Terminal Half Life | 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. | 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. |
| Pharmacokinetics - Clearance of Drug (Cl) | 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. | 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. |
| Pharmacokinetics - Volume of Distribution (Vz) | 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. | 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. |
| Plasma Gb3 Concentrations | Plasma Gb3 concentration (ug/mL) was measured at baseline and every 3 months up to 12 months. | Results are presented as mean percent change from baseline (visit 1) to 12 months +/- standard error. |
| Number of Participants With Anti-Drug Antibodies | 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. | 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. |
| Change in Short Form Brief Pain Inventory (BPI) | The Short Form Brief Pain Inventory (BPI) is assessed at baseline, 3-month, 6-month, and 12-month visits. | 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. |
| Urine Creatinine Level | Urine creatinine level is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits using spot urine tests. | 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 Protein/Creatinine Ratio | Protein/.creatinine ratio is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits | 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. |
| Total Urine Protein Level | Total urine protein level is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits. | 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. |
| Brain MRI | Brain MRI is performed at baseline and 12-month visit. | 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. |
| Change in Mainz Severity Score Index (MSSI) | The MSSI is performed at baseline, 6-month, and 12-month | 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. |
| Gastrointestinal Symptoms Questionnaire - Severity of Abdominal Pain | The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits. | 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. |
| Gastrointestinal Symptoms Questionnaire - Frequency of Abdominal Pain | The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits. | 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. |
| Gastrointestinal Symptoms Questionnaire - Frequency of Diarrhea | The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits. | 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. |
| Pharmacokinetics - Cmax | 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. | 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. |
Countries
Australia, Paraguay, Serbia, Spain, United Kingdom, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 0.2 mg/kg PRX-102 0.2 mg/kg every 2 weeks
PRX-102 | 6 |
| 1 mg/kg PRX-102 1 mg/kg every 2 weeks
PRX-102 | 8 |
| 2 mg/kg PRX-102 2 mg/kg every 2 weeks
PRX-102 | 4 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| PB-102-F01 | Adverse Event | 0 | 1 | 0 |
| PB-102-F01 | Physician Decision | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 0.2 mg/kg | 1 mg/kg | 2 mg/kg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 7 Participants | 4 Participants | 17 Participants |
| Phenotypically Classic vs Non Classic Fabry Patients Non Classic Fabry Patients | 1 Participants | 2 Participants | 3 Participants | 6 Participants |
| Phenotypically Classic vs Non Classic Fabry Patients Phenotypically Classic Fabry Patients | 5 Participants | 4 Participants | 1 Participants | 10 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 1 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 8 | 0 / 4 |
| other Total, other adverse events | 2 / 6 | 7 / 8 | 2 / 4 |
| serious Total, serious adverse events | 0 / 6 | 1 / 8 | 1 / 4 |
Outcome results
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.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Safety Group | Adverse Events | 54 adverse events |
| 0.2 mg/kg | Adverse Events | 11 adverse events |
| 1.0 mg/kg | Adverse Events | 29 adverse events |
| 2.0 mg/kg | Adverse Events | 14 adverse events |
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.
Time frame: Brain MRI is performed at baseline and 12-month visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety Group | Brain MRI | 0 Participants |
| 0.2 mg/kg | Brain MRI | 0 Participants |
| 1.0 mg/kg | Brain MRI | 0 Participants |
| 2.0 mg/kg | Brain MRI | 0 Participants |
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.
Time frame: Cardiac MRI was performed in order to assess myocardial fibrosis at baseline, 6 months and 12 months visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Safety Group | Cardiac Fibrosis Per MRI | 0 number of subjects |
| 0.2 mg/kg | Cardiac Fibrosis Per MRI | 0 number of subjects |
Other Pre-specified
Cardiac MRI - Ejection Fraction
Results are presented as mean percent change from baseline (visit 1) to 12 months.
Time frame: Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safety Group | Cardiac MRI - Ejection Fraction | -3.1 Percent Change | Standard Error 3.6 |
| 0.2 mg/kg | Cardiac MRI - Ejection Fraction | -7.3 Percent Change | Standard Error 3.2 |
Other Pre-specified
Cardiac MRI - LVM
Results are presented as mean percent change from baseline (visit 1) to 12 months.
Time frame: Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safety Group | Cardiac MRI - LVM | 0 Percent change | Standard Error 2.5 |
| 0.2 mg/kg | Cardiac MRI - LVM | -2.6 Percent change | Standard Error 3.4 |
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.
Time frame: Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safety Group | Cardiac MRI - LVMI | 0.4 Percent Change | Standard Error 2.6 |
| 0.2 mg/kg | Cardiac MRI - LVMI | -3.1 Percent Change | Standard Error 3.1 |
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.
Time frame: 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).
Population: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safety Group | Change in Kidney Gb3 Accumulation | -67.8 Percent change | Standard Error 8.9 |
| 0.2 mg/kg | Change in Kidney Gb3 Accumulation | -84.1 Percent change | Standard Error 3.4 |
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.
Time frame: The MSSI is performed at baseline, 6-month, and 12-month
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safety Group | Change in Mainz Severity Score Index (MSSI) | -2.8 score of a scale | Standard Error 1.2 |
| 0.2 mg/kg | Change in Mainz Severity Score Index (MSSI) | -1.2 score of a scale | Standard Error 0.6 |
| 1.0 mg/kg | Change in Mainz Severity Score Index (MSSI) | -1.5 score of a scale | Standard Error 0.9 |
| 2.0 mg/kg | Change in Mainz Severity Score Index (MSSI) | -1.9 score of a scale | Standard Error 0.6 |
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.
Time frame: The Short Form Brief Pain Inventory (BPI) is assessed at baseline, 3-month, 6-month, and 12-month visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safety Group | Change in Short Form Brief Pain Inventory (BPI) | -0.7 score on a scale | Standard Error 0.4 |
| 0.2 mg/kg | Change in Short Form Brief Pain Inventory (BPI) | -1.2 score on a scale | Standard Error 0.4 |
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.
Time frame: The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety Group | Gastrointestinal Symptoms Questionnaire - Frequency of Abdominal Pain | 7 Participants |
| 0.2 mg/kg | Gastrointestinal Symptoms Questionnaire - Frequency of Abdominal Pain | 5 Participants |
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.
Time frame: The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Safety Group | Gastrointestinal Symptoms Questionnaire - Frequency of Diarrhea | 11 Participants |
| 0.2 mg/kg | Gastrointestinal Symptoms Questionnaire - Frequency of Diarrhea | 6 Participants |
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.
Time frame: The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Safety Group | Gastrointestinal Symptoms Questionnaire - Severity of Abdominal Pain | 10 participants |
| 0.2 mg/kg | Gastrointestinal Symptoms Questionnaire - Severity of Abdominal Pain | 7 participants |
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.
Time frame: eGFR is performed at baseline (day 1) weeks 4, 8, 12, 26, 38 and 52 (12 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safety Group | Kidney Function - Change in eGFR | -0.8 mL/min/1.73 m2 | Standard Error 1.9 |
| 0.2 mg/kg | Kidney Function - Change in eGFR | 0 mL/min/1.73 m2 | Standard Error 2.8 |
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Safety Group | Number of Participants With Anti-Drug Antibodies | 2 participants |
| 0.2 mg/kg | Number of Participants With Anti-Drug Antibodies | 1 participants |
| 1.0 mg/kg | Number of Participants With Anti-Drug Antibodies | 0 participants |
| 2.0 mg/kg | Number of Participants With Anti-Drug Antibodies | 3 participants |
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safety Group | Pharmacokinetics - AUC | 70070 ng*hr/ml | Standard Error 26044 |
| 0.2 mg/kg | Pharmacokinetics - AUC | 390896 ng*hr/ml | Standard Error 136476 |
| 1.0 mg/kg | Pharmacokinetics - AUC | 619393 ng*hr/ml | Standard Error 158562 |
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safety Group | Pharmacokinetics - Clearance of Drug (Cl) | 2.96 ml/hr/kg | Standard Error 0.81 |
| 0.2 mg/kg | Pharmacokinetics - Clearance of Drug (Cl) | 2.85 ml/hr/kg | Standard Error 0.66 |
| 1.0 mg/kg | Pharmacokinetics - Clearance of Drug (Cl) | 3.41 ml/hr/kg | Standard Error 0.68 |
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safety Group | Pharmacokinetics - Cmax | 1858 ng/ml | Standard Error 531 |
| 0.2 mg/kg | Pharmacokinetics - Cmax | 11123 ng/ml | Standard Error 2409 |
| 1.0 mg/kg | Pharmacokinetics - Cmax | 16625 ng/ml | Standard Error 4299 |
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safety Group | Pharmacokinetics - Terminal Half Life | 60.3 hour | Standard Error 19.6 |
| 0.2 mg/kg | Pharmacokinetics - Terminal Half Life | 78.9 hour | Standard Error 10.3 |
| 1.0 mg/kg | Pharmacokinetics - Terminal Half Life | 70.7 hour | Standard Error 18 |
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safety Group | Pharmacokinetics - Volume of Distribution (Vz) | 246 ml/kg | Standard Error 68 |
| 0.2 mg/kg | Pharmacokinetics - Volume of Distribution (Vz) | 321 ml/kg | Standard Error 71 |
| 1.0 mg/kg | Pharmacokinetics - Volume of Distribution (Vz) | 345 ml/kg | Standard Error 105 |
Other Pre-specified
Plasma Gb3 Concentrations
Results are presented as mean percent change from baseline (visit 1) to 12 months +/- standard error.
Time frame: Plasma Gb3 concentration (ug/mL) was measured at baseline and every 3 months up to 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safety Group | Plasma Gb3 Concentrations | -16.8 mean percent change | Standard Error 8.6 |
| 0.2 mg/kg | Plasma Gb3 Concentrations | -30.7 mean percent change | Standard Error 11.2 |
| 1.0 mg/kg | Plasma Gb3 Concentrations | -16.2 mean percent change | Standard Error 12.7 |
| 2.0 mg/kg | Plasma Gb3 Concentrations | -22.2 mean percent change | Standard Error 6.1 |
| Phenotypically Classic Fabry Patients | Plasma Gb3 Concentrations | -33.3 mean percent change | Standard Error 7.6 |
Other Pre-specified
Plasma Lyso-Gb3 Levels
Results are presented as mean percent change from baseline (visit 1) to 12 months +/- standard error.
Time frame: Plasma Lyso-Gb3 concentration (ng/mL) was measured at baseline and every 3 months up to 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safety Group | Plasma Lyso-Gb3 Levels | -43.4 mean percent change | Standard Error 12.2 |
| 0.2 mg/kg | Plasma Lyso-Gb3 Levels | -59.9 mean percent change | Standard Error 7.1 |
| 1.0 mg/kg | Plasma Lyso-Gb3 Levels | -40.4 mean percent change | Standard Error 7.5 |
| 2.0 mg/kg | Plasma Lyso-Gb3 Levels | -48.9 mean percent change | Standard Error 5.7 |
| Phenotypically Classic Fabry Patients | Plasma Lyso-Gb3 Levels | -57.6 mean percent change | Standard Error 6.8 |
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.
Time frame: Total urine protein level is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safety Group | Total Urine Protein Level | -35.1 Percentage change from baseline | Standard Error 18.4 |
| 0.2 mg/kg | Total Urine Protein Level | -32.8 Percentage change from baseline | Standard Error 17.4 |
| 1.0 mg/kg | Total Urine Protein Level | -71.7 Percentage change from baseline | Standard Error 7.3 |
| 2.0 mg/kg | Total Urine Protein Level | -43.4 Percentage change from baseline | Standard Error 9.9 |
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.
Time frame: Urine creatinine level is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits using spot urine tests.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safety Group | Urine Creatinine Level | -15.9 Percentage change from baseline | Standard Error 25.6 |
| 0.2 mg/kg | Urine Creatinine Level | -15.3 Percentage change from baseline | Standard Error 27.8 |
| 1.0 mg/kg | Urine Creatinine Level | -68.3 Percentage change from baseline | Standard Error 2.5 |
| 2.0 mg/kg | Urine Creatinine Level | -28.8 Percentage change from baseline | Standard Error 14.6 |
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.
Time frame: Protein/.creatinine ratio is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Safety Group | Urine Protein/Creatinine Ratio | -2.6 Percentage change from baseline | Standard Error 23.4 |
| 0.2 mg/kg | Urine Protein/Creatinine Ratio | -14.8 Percentage change from baseline | Standard Error 14.1 |
| 1.0 mg/kg | Urine Protein/Creatinine Ratio | -7.9 Percentage change from baseline | Standard Error 12.4 |
| 2.0 mg/kg | Urine Protein/Creatinine Ratio | -8.5 Percentage change from baseline | Standard Error 10.1 |