<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01678898</url>
  </required_header>
  <id_info>
    <org_study_id>PB-102-F01 &amp; PB-102-F02</org_study_id>
    <nct_id>NCT01678898</nct_id>
    <nct_alias>NCT01769001</nct_alias>
  </id_info>
  <brief_title>Dose-ranging Study of PRX-102 in Adult Fabry Disease Patients</brief_title>
  <official_title>A Phase 1/2, Open Label, Dose Ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Exploratory Efficacy Parameters of PRX-102 Administered by Intravenous Infusion Every 2 Weeks for 12 Months to Adult Fabry Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Protalix</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chiesi Farmaceutici S.p.A.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Protalix</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is the first human treatment with PRX-102, an enzyme being developed as a long-term&#xD;
      enzyme replacement therapy in patients with a confirmed diagnosis of Fabry disease (alpha&#xD;
      galactosidase deficiency). The safety, tolerability, and exploratory efficacy will be&#xD;
      evaluated in this study of increasing doses. Patients will be treated with infusions every&#xD;
      two weeks for 12 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Under the PB-102-F01 study protocol, patients will be enrolled into one of three PRX-102&#xD;
      dosing groups (0.2 mg/kg, 1.0 mg/kg, 2.0 mg/kg) and receive PRX-102 as an intravenous&#xD;
      infusion every 2 weeks for 12 weeks (3 months). Patients who finish the PB-102-F01 study will&#xD;
      be enrolled in the PB-102-F02 extension study and receive the same dose they had received in&#xD;
      the PB-102-F01 study for an additional 38 weeks (9 months).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2012</start_date>
  <completion_date type="Actual">March 6, 2016</completion_date>
  <primary_completion_date type="Actual">March 6, 2016</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>12 months</time_frame>
    <description>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.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Plasma Gb3 Concentrations</measure>
    <time_frame>Plasma Gb3 concentration (ug/mL) was measured at baseline and every 3 months up to 12 months.</time_frame>
    <description>Results are presented as mean percent change from baseline (visit 1) to 12 months +/- standard error.</description>
  </other_outcome>
  <other_outcome>
    <measure>Kidney Function - Change in eGFR</measure>
    <time_frame>eGFR is performed at baseline (day 1) weeks 4, 8, 12, 26, 38 and 52 (12 months)</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Plasma Lyso-Gb3 Levels</measure>
    <time_frame>Plasma Lyso-Gb3 concentration (ng/mL) was measured at baseline and every 3 months up to 12 months.</time_frame>
    <description>Results are presented as mean percent change from baseline (visit 1) to 12 months +/- standard error.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Kidney Gb3 Accumulation</measure>
    <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).</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Cardiac Fibrosis Per MRI</measure>
    <time_frame>Cardiac MRI was performed in order to assess myocardial fibrosis at baseline, 6 months and 12 months visit.</time_frame>
    <description>Cardiac MRI was performed to estimate the percentage and mass of the myocardial fibrotic area.&#xD;
Results represent the number of subjects with fibrosis after 1 year of treatment.</description>
  </other_outcome>
  <other_outcome>
    <measure>Cardiac MRI - Ejection Fraction</measure>
    <time_frame>Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months.</time_frame>
    <description>Results are presented as mean percent change from baseline (visit 1) to 12 months.</description>
  </other_outcome>
  <other_outcome>
    <measure>Cardiac MRI - LVM</measure>
    <time_frame>Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months.</time_frame>
    <description>Results are presented as mean percent change from baseline (visit 1) to 12 months.</description>
  </other_outcome>
  <other_outcome>
    <measure>Cardiac MRI - LVMI</measure>
    <time_frame>Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months.</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacokinetics - AUC</measure>
    <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.</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacokinetics - Terminal Half Life</measure>
    <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.</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacokinetics - Clearance of Drug (Cl)</measure>
    <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.</time_frame>
    <description>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.&#xD;
Results reported represent the averaged values following a single dosing of the study drug.</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacokinetics - Volume of Distribution (Vz)</measure>
    <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.</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Pharmacokinetics - Cmax</measure>
    <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.</time_frame>
    <description>Pharmacokinetic (PK) parameters were derived from the plasma concentration versus time profiles.&#xD;
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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of Participants With Anti-Drug Antibodies</measure>
    <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.</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Short Form Brief Pain Inventory (BPI)</measure>
    <time_frame>The Short Form Brief Pain Inventory (BPI) is assessed at baseline, 3-month, 6-month, and 12-month visits.</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Urine Creatinine Level</measure>
    <time_frame>Urine creatinine level is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits using spot urine tests.</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Urine Protein/Creatinine Ratio</measure>
    <time_frame>Protein/.creatinine ratio is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Total Urine Protein Level</measure>
    <time_frame>Total urine protein level is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits.</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Brain MRI</measure>
    <time_frame>Brain MRI is performed at baseline and 12-month visit.</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Mainz Severity Score Index (MSSI)</measure>
    <time_frame>The MSSI is performed at baseline, 6-month, and 12-month</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Gastrointestinal Symptoms Questionnaire - Severity of Abdominal Pain</measure>
    <time_frame>The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits.</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Gastrointestinal Symptoms Questionnaire - Frequency of Abdominal Pain</measure>
    <time_frame>The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits.</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>Gastrointestinal Symptoms Questionnaire - Frequency of Diarrhea</measure>
    <time_frame>The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits.</time_frame>
    <description>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.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Fabry Disease</condition>
  <arm_group>
    <arm_group_label>0.2 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PRX-102 0.2 mg/kg every 2 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PRX-102 1 mg/kg every 2 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2 mg/kg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PRX-102 2 mg/kg every 2 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PRX-102</intervention_name>
    <arm_group_label>0.2 mg/kg</arm_group_label>
    <arm_group_label>1 mg/kg</arm_group_label>
    <arm_group_label>2 mg/kg</arm_group_label>
    <other_name>plant cell expressed recombinant human alpha-galactosidase-A</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Symptomatic adult Fabry patients (≥18 yrs)&#xD;
&#xD;
          -  Males: plasma and/or leucocyte alpha galactosidase activity (by activity assay) less&#xD;
             than lower limit of normal (LLN in plasma=3.2 nmol/hr/ml, LLN in leucocytes=32&#xD;
             nmol/hr/mg/protein)&#xD;
&#xD;
          -  Females: historical genetic test results consistent with Fabry mutations&#xD;
&#xD;
          -  Globotriaosylceramide (Gb3) concentration in urine &gt; 1.5 times upper normal limit&#xD;
&#xD;
          -  Patients who have never received enzyme replacement therapy (ERT) in the past, or&#xD;
             patients who have not received ERT in the past 6 months and have a negative anti alpha&#xD;
             galactosidase antibody test&#xD;
&#xD;
          -  eGFR ≥ 60 mL/min/1.73m2&#xD;
&#xD;
          -  The patient signs informed consent&#xD;
&#xD;
          -  Female patients and male patients whose co-partners are of child-bearing potential&#xD;
             agree to use a medically acceptable method of contraception, not including the rhythm&#xD;
             method&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participation in any trial of an investigational drug within 30 days prior to study&#xD;
             screening&#xD;
&#xD;
          -  Chronic kidney disease stages 3-5 (CKD 3-5) (Appendix 7)&#xD;
&#xD;
          -  History of dialysis or renal transplantation&#xD;
&#xD;
          -  Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)&#xD;
             therapy initiated or dose changed in the 4 weeks prior to screening&#xD;
&#xD;
          -  Severe myocardial fibrosis by MRI (≥2 late-enhancement [LE] positive left ventricular&#xD;
             segments) (Weidemann et al. 2009)&#xD;
&#xD;
          -  History of clinical stroke&#xD;
&#xD;
          -  Pregnant or nursing&#xD;
&#xD;
          -  Presence of HIV and/or HBsAg and/or Hepatitis C infections&#xD;
&#xD;
          -  Known allergies to ERT&#xD;
&#xD;
          -  Known allergy to Gadolinium based contrast agents&#xD;
&#xD;
          -  Presence of any medical, emotional, behavioral or psychological condition that, in the&#xD;
             judgment of the Investigator and/or Medical Director, would interfere with the&#xD;
             patient's compliance with the requirements of the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>UC Davis Medical Center, MIND Institute Department of Pediatrics, Section of Genetics</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Human Genetics, Emory University School of Medicine</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa Health Clinics</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University School of Medicine</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Pittsburgh of UPMC</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Baylor Institute of Metabolic Disease</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>O &amp; O Alpan LLC</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Melbourne Hospital</name>
      <address>
        <city>Victoria Park</city>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hematology and Clinical Research Private Institute</name>
      <address>
        <city>Asuncion</city>
        <country>Paraguay</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Center of Serbia</name>
      <address>
        <city>Belgrade</city>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Dia Quiron Zaragoza</name>
      <address>
        <city>Zaragoza</city>
        <zip>50012</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal Free Hospital</name>
      <address>
        <city>London</city>
        <zip>NW3 2QG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Paraguay</country>
    <country>Serbia</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>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.</citation>
    <PMID>30834538</PMID>
  </results_reference>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>August 31, 2012</study_first_submitted>
  <study_first_submitted_qc>September 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2012</study_first_posted>
  <results_first_submitted>August 27, 2019</results_first_submitted>
  <results_first_submitted_qc>January 14, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 27, 2020</results_first_posted>
  <last_update_submitted>September 10, 2023</last_update_submitted>
  <last_update_submitted_qc>September 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Fabry disease</keyword>
  <keyword>Alpha galactosidase deficiency</keyword>
  <keyword>Metabolic storage disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fabry Disease</mesh_term>
  </condition_browse>

  <clinical_results>

    <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.</recruitment_details>
      <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.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>0.2 mg/kg</title>
          <description>PRX-102 0.2 mg/kg every 2 weeks&#xD;
PRX-102</description>
        </group>
        <group group_id="P2">
          <title>1 mg/kg</title>
          <description>PRX-102 1 mg/kg every 2 weeks&#xD;
PRX-102</description>
        </group>
        <group group_id="P3">
          <title>2 mg/kg</title>
          <description>PRX-102 2 mg/kg every 2 weeks&#xD;
PRX-102</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>PB-102-F01</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>PB-102-F02</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>0.2 mg/kg</title>
          <description>PRX-102 0.2 mg/kg every 2 weeks&#xD;
PRX-102</description>
        </group>
        <group group_id="B2">
          <title>1 mg/kg</title>
          <description>PRX-102 1 mg/kg every 2 weeks&#xD;
PRX-102</description>
        </group>
        <group group_id="B3">
          <title>2 mg/kg</title>
          <description>PRX-102 2 mg/kg every 2 weeks&#xD;
PRX-102</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="8"/>
            <count group_id="B3" value="4"/>
            <count group_id="B4" value="18"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="8"/>
                    <count group_id="B3" value="4"/>
                    <count group_id="B4" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="8"/>
                    <count group_id="B3" value="4"/>
                    <count group_id="B4" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Phenotypically Classic vs Non Classic Fabry Patients</title>
          <population>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.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="6"/>
                    <count group_id="B3" value="4"/>
                    <count group_id="B4" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Phenotypically Classic Fabry Patients</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Non Classic Fabry Patients</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Adverse Events</title>
        <description>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.</description>
        <time_frame>12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Safety Group</title>
            <description>The safety population in the study included 18 patients: 6 patients in the 0.2 mg/kg treatment group, 8 patients in the 1.0 mg/kg, and 4 patients in the 2.0 mg/kg treatment groups.</description>
          </group>
          <group group_id="O2">
            <title>0.2 mg/kg</title>
            <description>PRX-102 0.2 mg/kg every 2 weeks</description>
          </group>
          <group group_id="O3">
            <title>1.0 mg/kg</title>
            <description>PRX-102 1.0 mg/kg every 2 weeks</description>
          </group>
          <group group_id="O4">
            <title>2.0 mg/kg</title>
            <description>PRX-102 2.0 mg/kg every 2 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Adverse Events</title>
          <description>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.</description>
          <units>adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54"/>
                    <measurement group_id="O2" value="11"/>
                    <measurement group_id="O3" value="29"/>
                    <measurement group_id="O4" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Plasma Gb3 Concentrations</title>
        <description>Results are presented as mean percent change from baseline (visit 1) to 12 months +/- standard error.</description>
        <time_frame>Plasma Gb3 concentration (ug/mL) was measured at baseline and every 3 months up to 12 months.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.2 mg/kg</title>
            <description>PRX-102 0.2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O2">
            <title>1 mg/kg</title>
            <description>PRX-102 1 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O3">
            <title>2 mg/kg</title>
            <description>PRX-102 2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O4">
            <title>Efficacy Group</title>
            <description>The efficacy group includes all the subjects that completed the study.</description>
          </group>
          <group group_id="O5">
            <title>Phenotypically Classic Fabry Patients</title>
            <description>Patients who are phenotypically classic Fabry Patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma Gb3 Concentrations</title>
          <description>Results are presented as mean percent change from baseline (visit 1) to 12 months +/- standard error.</description>
          <units>mean percent change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="16"/>
                <count group_id="O5" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16.8" spread="8.6"/>
                    <measurement group_id="O2" value="-30.7" spread="11.2"/>
                    <measurement group_id="O3" value="-16.2" spread="12.7"/>
                    <measurement group_id="O4" value="-22.2" spread="6.1"/>
                    <measurement group_id="O5" value="-33.3" spread="7.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Kidney Function - Change in eGFR</title>
        <description>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.</description>
        <time_frame>eGFR is performed at baseline (day 1) weeks 4, 8, 12, 26, 38 and 52 (12 months)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pegunigalsidase Alfa Reporting Group</title>
            <description>All 16 patients in the efficacy group, including both phenotypically classic Fabry patients and non classic Fabry patients.</description>
          </group>
          <group group_id="O2">
            <title>Phenotypically Classic Fabry Patients</title>
            <description>10 patients who are phenotypically classic Fabry patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Kidney Function - Change in eGFR</title>
          <description>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.</description>
          <units>mL/min/1.73 m2</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" spread="1.9"/>
                    <measurement group_id="O2" value="0" spread="2.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Plasma Lyso-Gb3 Levels</title>
        <description>Results are presented as mean percent change from baseline (visit 1) to 12 months +/- standard error.</description>
        <time_frame>Plasma Lyso-Gb3 concentration (ng/mL) was measured at baseline and every 3 months up to 12 months.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.2 mg/kg</title>
            <description>PRX-102 0.2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O2">
            <title>1 mg/kg</title>
            <description>PRX-102 1 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O3">
            <title>2 mg/kg</title>
            <description>PRX-102 2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O4">
            <title>Efficacy Group</title>
            <description>The efficacy group includes all the subjects that completed the study.</description>
          </group>
          <group group_id="O5">
            <title>Phenotypically Classic Fabry Patients</title>
            <description>Patients who are phenotypically classic Fabry patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma Lyso-Gb3 Levels</title>
          <description>Results are presented as mean percent change from baseline (visit 1) to 12 months +/- standard error.</description>
          <units>mean percent change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="16"/>
                <count group_id="O5" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-43.4" spread="12.2"/>
                    <measurement group_id="O2" value="-59.9" spread="7.1"/>
                    <measurement group_id="O3" value="-40.4" spread="7.5"/>
                    <measurement group_id="O4" value="-48.9" spread="5.7"/>
                    <measurement group_id="O5" value="-57.6" spread="6.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Kidney Gb3 Accumulation</title>
        <description>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.</description>
        <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).</time_frame>
        <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</population>
        <group_list>
          <group group_id="O1">
            <title>Pegunigalsidase Alfa Reporting Group</title>
            <description>All 16 patients in the efficacy group, including both phenotypically classic Fabry patients and non classic Fabry patients.</description>
          </group>
          <group group_id="O2">
            <title>Phenotypically Classic Fabry Patients</title>
            <description>10 patients who are phenotypically classic Fabry patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Kidney Gb3 Accumulation</title>
          <description>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.</description>
          <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</population>
          <units>Percent change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-67.8" spread="8.9"/>
                    <measurement group_id="O2" value="-84.1" spread="3.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Cardiac Fibrosis Per MRI</title>
        <description>Cardiac MRI was performed to estimate the percentage and mass of the myocardial fibrotic area.&#xD;
Results represent the number of subjects with fibrosis after 1 year of treatment.</description>
        <time_frame>Cardiac MRI was performed in order to assess myocardial fibrosis at baseline, 6 months and 12 months visit.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pegunigalsidase Alfa Reporting Group</title>
            <description>All 16 patients in the efficacy group, including both phenotypically classic Fabry patients and non classic Fabry patients.</description>
          </group>
          <group group_id="O2">
            <title>Phenotypically Classic Fabry Patients</title>
            <description>10 patients who are phenotypically classic Fabry patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Cardiac Fibrosis Per MRI</title>
          <description>Cardiac MRI was performed to estimate the percentage and mass of the myocardial fibrotic area.&#xD;
Results represent the number of subjects with fibrosis after 1 year of treatment.</description>
          <units>number of subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Cardiac MRI - Ejection Fraction</title>
        <description>Results are presented as mean percent change from baseline (visit 1) to 12 months.</description>
        <time_frame>Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pegunigalsidase Alfa Reporting Group</title>
            <description>All 16 patients in the efficacy group, including both phenotypically classic Fabry patients and non classic Fabry patients.</description>
          </group>
          <group group_id="O2">
            <title>Phenotypically Classic Fabry Patients</title>
            <description>10 patients who are phenotypically classic Fabry patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Cardiac MRI - Ejection Fraction</title>
          <description>Results are presented as mean percent change from baseline (visit 1) to 12 months.</description>
          <units>Percent Change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.1" spread="3.6"/>
                    <measurement group_id="O2" value="-7.3" spread="3.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Cardiac MRI - LVM</title>
        <description>Results are presented as mean percent change from baseline (visit 1) to 12 months.</description>
        <time_frame>Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pegunigalsidase Alfa Reporting Group</title>
            <description>All 16 patients in the efficacy group, including both phenotypically classic Fabry patients and non classic Fabry patients.</description>
          </group>
          <group group_id="O2">
            <title>Phenotypically Classic Fabry Patients</title>
            <description>10 patients who are phenotypically classic Fabry patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Cardiac MRI - LVM</title>
          <description>Results are presented as mean percent change from baseline (visit 1) to 12 months.</description>
          <units>Percent change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="2.5"/>
                    <measurement group_id="O2" value="-2.6" spread="3.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Cardiac MRI - LVMI</title>
        <description>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.</description>
        <time_frame>Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pegunigalsidase Alfa Reporting Group</title>
            <description>All 16 patients in the efficacy group, including both phenotypically classic Fabry patients and non classic Fabry patients.</description>
          </group>
          <group group_id="O2">
            <title>Phenotypically Classic Fabry Patients</title>
            <description>10 patients who are phenotypically classic Fabry patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Cardiac MRI - LVMI</title>
          <description>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.</description>
          <units>Percent Change</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="2.6"/>
                    <measurement group_id="O2" value="-3.1" spread="3.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Pharmacokinetics - AUC</title>
        <description>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.</description>
        <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.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.2 mg/kg</title>
            <description>PRX-102 0.2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O2">
            <title>1 mg/kg</title>
            <description>PRX-102 1 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O3">
            <title>2 mg/kg</title>
            <description>PRX-102 2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics - AUC</title>
          <description>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.</description>
          <units>ng*hr/ml</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70070" spread="26044"/>
                    <measurement group_id="O2" value="390896" spread="136476"/>
                    <measurement group_id="O3" value="619393" spread="158562"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Pharmacokinetics - Terminal Half Life</title>
        <description>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.</description>
        <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.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.2 mg/kg</title>
            <description>PRX-102 0.2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O2">
            <title>1 mg/kg</title>
            <description>PRX-102 1 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O3">
            <title>2 mg/kg</title>
            <description>PRX-102 2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics - Terminal Half Life</title>
          <description>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.</description>
          <units>hour</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.3" spread="19.6"/>
                    <measurement group_id="O2" value="78.9" spread="10.3"/>
                    <measurement group_id="O3" value="70.7" spread="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Pharmacokinetics - Clearance of Drug (Cl)</title>
        <description>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.&#xD;
Results reported represent the averaged values following a single dosing of the study drug.</description>
        <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.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.2 mg/kg</title>
            <description>PRX-102 0.2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O2">
            <title>1 mg/kg</title>
            <description>PRX-102 1 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O3">
            <title>2 mg/kg</title>
            <description>PRX-102 2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics - Clearance of Drug (Cl)</title>
          <description>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.&#xD;
Results reported represent the averaged values following a single dosing of the study drug.</description>
          <units>ml/hr/kg</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.96" spread="0.81"/>
                    <measurement group_id="O2" value="2.85" spread="0.66"/>
                    <measurement group_id="O3" value="3.41" spread="0.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Pharmacokinetics - Volume of Distribution (Vz)</title>
        <description>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.</description>
        <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.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.2 mg/kg</title>
            <description>PRX-102 0.2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O2">
            <title>1 mg/kg</title>
            <description>PRX-102 1 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O3">
            <title>2 mg/kg</title>
            <description>PRX-102 2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics - Volume of Distribution (Vz)</title>
          <description>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.</description>
          <units>ml/kg</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="246" spread="68"/>
                    <measurement group_id="O2" value="321" spread="71"/>
                    <measurement group_id="O3" value="345" spread="105"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Pharmacokinetics - Cmax</title>
        <description>Pharmacokinetic (PK) parameters were derived from the plasma concentration versus time profiles.&#xD;
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.</description>
        <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.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.2 mg/kg</title>
            <description>PRX-102 0.2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O2">
            <title>1 mg/kg</title>
            <description>PRX-102 1 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O3">
            <title>2 mg/kg</title>
            <description>PRX-102 2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics - Cmax</title>
          <description>Pharmacokinetic (PK) parameters were derived from the plasma concentration versus time profiles.&#xD;
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.</description>
          <units>ng/ml</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1858" spread="531"/>
                    <measurement group_id="O2" value="11123" spread="2409"/>
                    <measurement group_id="O3" value="16625" spread="4299"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants With Anti-Drug Antibodies</title>
        <description>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.</description>
        <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.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.2 mg/kg</title>
            <description>PRX-102 0.2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O2">
            <title>1 mg/kg</title>
            <description>PRX-102 1 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O3">
            <title>2 mg/kg</title>
            <description>PRX-102 2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O4">
            <title>Efficacy Group</title>
            <description>The efficacy group includes all the subjects that completed the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Anti-Drug Antibodies</title>
          <description>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.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Short Form Brief Pain Inventory (BPI)</title>
        <description>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.</description>
        <time_frame>The Short Form Brief Pain Inventory (BPI) is assessed at baseline, 3-month, 6-month, and 12-month visits.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pegunigalsidase Alfa Reporting Group</title>
            <description>All 16 patients in the efficacy group, including both phenotypically classic Fabry patients and non classic Fabry patients.</description>
          </group>
          <group group_id="O2">
            <title>Phenotypically Classic Fabry Patients</title>
            <description>10 patients who are phenotypically classic Fabry patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Short Form Brief Pain Inventory (BPI)</title>
          <description>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.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.7" spread="0.4"/>
                    <measurement group_id="O2" value="-1.2" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Urine Creatinine Level</title>
        <description>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.</description>
        <time_frame>Urine creatinine level is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits using spot urine tests.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.2 mg/kg</title>
            <description>PRX-102 0.2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O2">
            <title>1 mg/kg</title>
            <description>PRX-102 1 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O3">
            <title>2 mg/kg</title>
            <description>PRX-102 2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O4">
            <title>Efficacy Group</title>
            <description>The efficacy group includes all the subjects that completed the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Urine Creatinine Level</title>
          <description>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.</description>
          <units>Percentage change from baseline</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.9" spread="25.6"/>
                    <measurement group_id="O2" value="-15.3" spread="27.8"/>
                    <measurement group_id="O3" value="-68.3" spread="2.5"/>
                    <measurement group_id="O4" value="-28.8" spread="14.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Urine Protein/Creatinine Ratio</title>
        <description>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.</description>
        <time_frame>Protein/.creatinine ratio is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.2 mg/kg</title>
            <description>PRX-102 0.2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O2">
            <title>1 mg/kg</title>
            <description>PRX-102 1 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O3">
            <title>2 mg/kg</title>
            <description>PRX-102 2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O4">
            <title>Efficacy Group</title>
            <description>The efficacy group includes all the subjects that completed the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Urine Protein/Creatinine Ratio</title>
          <description>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.</description>
          <units>Percentage change from baseline</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.6" spread="23.4"/>
                    <measurement group_id="O2" value="-14.8" spread="14.1"/>
                    <measurement group_id="O3" value="-7.9" spread="12.4"/>
                    <measurement group_id="O4" value="-8.5" spread="10.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Total Urine Protein Level</title>
        <description>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.</description>
        <time_frame>Total urine protein level is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.2 mg/kg</title>
            <description>PRX-102 0.2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O2">
            <title>1 mg/kg</title>
            <description>PRX-102 1 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O3">
            <title>2 mg/kg</title>
            <description>PRX-102 2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O4">
            <title>Efficacy Group</title>
            <description>The efficacy group includes all the subjects that completed the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Urine Protein Level</title>
          <description>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.</description>
          <units>Percentage change from baseline</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-35.1" spread="18.4"/>
                    <measurement group_id="O2" value="-32.8" spread="17.4"/>
                    <measurement group_id="O3" value="-71.7" spread="7.3"/>
                    <measurement group_id="O4" value="-43.4" spread="9.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Brain MRI</title>
        <description>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.</description>
        <time_frame>Brain MRI is performed at baseline and 12-month visit.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.2 mg/kg</title>
            <description>PRX-102 0.2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O2">
            <title>1 mg/kg</title>
            <description>PRX-102 1 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O3">
            <title>2 mg/kg</title>
            <description>PRX-102 2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O4">
            <title>Efficacy Group</title>
            <description>The efficacy group includes all the subjects that completed the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Brain MRI</title>
          <description>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.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Mainz Severity Score Index (MSSI)</title>
        <description>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.</description>
        <time_frame>The MSSI is performed at baseline, 6-month, and 12-month</time_frame>
        <group_list>
          <group group_id="O1">
            <title>0.2 mg/kg</title>
            <description>PRX-102 0.2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O2">
            <title>1 mg/kg</title>
            <description>PRX-102 1 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O3">
            <title>2 mg/kg</title>
            <description>PRX-102 2 mg/kg every 2 weeks&#xD;
PRX-102</description>
          </group>
          <group group_id="O4">
            <title>Efficacy Group</title>
            <description>The efficacy group includes all the subjects that completed the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Mainz Severity Score Index (MSSI)</title>
          <description>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.</description>
          <units>score of a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.8" spread="1.2"/>
                    <measurement group_id="O2" value="-1.2" spread="0.6"/>
                    <measurement group_id="O3" value="-1.5" spread="0.9"/>
                    <measurement group_id="O4" value="-1.9" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Gastrointestinal Symptoms Questionnaire - Severity of Abdominal Pain</title>
        <description>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.</description>
        <time_frame>The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pegunigalsidase Alfa Reporting Group</title>
            <description>All 16 patients in the efficacy group, including both phenotypically classic Fabry patients and non classic Fabry patients.</description>
          </group>
          <group group_id="O2">
            <title>Phenotypically Classic Fabry Patients</title>
            <description>10 patients who are phenotypically classic Fabry patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Gastrointestinal Symptoms Questionnaire - Severity of Abdominal Pain</title>
          <description>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.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Gastrointestinal Symptoms Questionnaire - Frequency of Abdominal Pain</title>
        <description>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.</description>
        <time_frame>The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pegunigalsidase Alfa Reporting Group</title>
            <description>All 16 patients in the efficacy group, including both phenotypically classic Fabry patients and non classic Fabry patients.</description>
          </group>
          <group group_id="O2">
            <title>Phenotypically Classic Fabry Patients</title>
            <description>10 patients who are phenotypically classic Fabry patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Gastrointestinal Symptoms Questionnaire - Frequency of Abdominal Pain</title>
          <description>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.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Gastrointestinal Symptoms Questionnaire - Frequency of Diarrhea</title>
        <description>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.</description>
        <time_frame>The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pegunigalsidase Alfa Reporting Group</title>
            <description>All 16 patients in the efficacy group, including both phenotypically classic Fabry patients and non classic Fabry patients.</description>
          </group>
          <group group_id="O2">
            <title>Phenotypically Classic Fabry Patients</title>
            <description>10 patients who are phenotypically classic Fabry patients.</description>
          </group>
        </group_list>
        <measure>
          <title>Gastrointestinal Symptoms Questionnaire - Frequency of Diarrhea</title>
          <description>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.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>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.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>0.2 mg/kg</title>
          <description>PRX-102 0.2 mg/kg every 2 weeks</description>
        </group>
        <group group_id="E2">
          <title>1 mg/kg</title>
          <description>PRX-102 1.0 mg/kg every 2 weeks</description>
        </group>
        <group group_id="E3">
          <title>2 mg/kg</title>
          <description>PRX-102 2.0 mg/kg every 2 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (16.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Renal Hematoma</sub_title>
                <description>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.</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bronchospasm</sub_title>
                <description>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</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (16.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="8"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Corneal Edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Conjunctival Hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="7" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Infusion reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Peripheral Edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="6" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal Stiffness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Visual field defect</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Typical aura without headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Nervousness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Sneezing</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Paranasal sinus hypersecretion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Bronchospasm</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Itching</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Sweating</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Raul Chertkoff</name_or_title>
      <organization>Protalix Ltd</organization>
      <phone>+972-4-9028100</phone>
      <email>raul@protalix.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01678898
org study id: PB-102-F01 & PB-102-F02
nct id: NCT01678898
nct alias: NCT01769001
lead sponsor: 
collaborator: 
has dmc: No
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).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Events
time frame: 12 months
description: 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.
measure: Plasma Gb3 Concentrations
time frame: Plasma Gb3 concentration (ug/mL) was measured at baseline and every 3 months up to 12 months.
description: Results are presented as mean percent change from baseline (visit 1) to 12 months +/- standard error.
measure: Kidney Function - Change in eGFR
time frame: eGFR is performed at baseline (day 1) weeks 4, 8, 12, 26, 38 and 52 (12 months)
description: 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.
measure: Plasma Lyso-Gb3 Levels
time frame: Plasma Lyso-Gb3 concentration (ng/mL) was measured at baseline and every 3 months up to 12 months.
description: Results are presented as mean percent change from baseline (visit 1) to 12 months +/- standard error.
measure: Change in Kidney Gb3 Accumulation
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).
description: 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.
measure: Cardiac Fibrosis Per MRI
time frame: Cardiac MRI was performed in order to assess myocardial fibrosis at baseline, 6 months and 12 months visit.
description: 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.
measure: Cardiac MRI - Ejection Fraction
time frame: Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months.
description: Results are presented as mean percent change from baseline (visit 1) to 12 months.
measure: Cardiac MRI - LVM
time frame: Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months.
description: Results are presented as mean percent change from baseline (visit 1) to 12 months.
measure: Cardiac MRI - LVMI
time frame: Cardiac MRI was performed 3 times: at baseline (visit 1), 6 months and 12 months.
description: 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.
measure: Pharmacokinetics - AUC
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.
description: 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.
measure: Pharmacokinetics - Terminal Half Life
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.
description: 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.
measure: Pharmacokinetics - Clearance of Drug (Cl)
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.
description: 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.
measure: Pharmacokinetics - Volume of Distribution (Vz)
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.
description: 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.
measure: Pharmacokinetics - Cmax
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.
description: 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.
measure: Number of Participants With Anti-Drug Antibodies
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.
description: 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.
measure: Change in Short Form Brief Pain Inventory (BPI)
time frame: The Short Form Brief Pain Inventory (BPI) is assessed at baseline, 3-month, 6-month, and 12-month visits.
description: 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.
measure: Urine Creatinine Level
time frame: Urine creatinine level is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits using spot urine tests.
description: 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.
measure: Urine Protein/Creatinine Ratio
time frame: Protein/.creatinine ratio is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits
description: 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.
measure: Total Urine Protein Level
time frame: Total urine protein level is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits.
description: 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.
measure: Brain MRI
time frame: Brain MRI is performed at baseline and 12-month visit.
description: 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.
measure: Change in Mainz Severity Score Index (MSSI)
time frame: The MSSI is performed at baseline, 6-month, and 12-month
description: 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.
measure: Gastrointestinal Symptoms Questionnaire - Severity of Abdominal Pain
time frame: The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits.
description: 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.
measure: Gastrointestinal Symptoms Questionnaire - Frequency of Abdominal Pain
time frame: The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits.
description: 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.
measure: Gastrointestinal Symptoms Questionnaire - Frequency of Diarrhea
time frame: The Gastrointestinal Symptoms Questionnaire is assessed at baseline, 3-month, 6-month, 9-month, and 12-month visits.
description: 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.
arm group label: 0.2 mg/kg
arm group type: Experimental
description: PRX-102 0.2 mg/kg every 2 weeks
arm group label: 1 mg/kg
arm group type: Experimental
description: PRX-102 1 mg/kg every 2 weeks
arm group label: 2 mg/kg
arm group type: Experimental
description: PRX-102 2 mg/kg every 2 weeks
intervention type: Drug
intervention name: PRX-102
arm group label: 0.2 mg/kg
arm group label: 1 mg/kg
arm group label: 2 mg/kg
other name: plant cell expressed recombinant human alpha-galactosidase-A
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Paraguay
country: Serbia
country: Spain
country: United Kingdom
country: United States
citation: 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.
PMID: 30834538
responsible party type: Sponsor
mesh term: Fabry Disease
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 