Dose-ranging Study of PRX-102 in Adult Fabry Disease Patients

• Gb3 concentrations [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  Gb3 concentrations in plasma and urine sediment
• Kidney function [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  Measurement of glomerular filtration and proteinuria
• Pain [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
  Short term brief pain inventory

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 weeks (7 infusions).

• Experimental: 0.2 mg/kg
  PRX-102 0.2 mg/kg every 2 weeks
  Intervention: Drug: PRX-102
• Experimental: 1 mg/kg
  PRX-102 1 mg/kg every 2 weeks
  Intervention: Drug: PRX-102
• Experimental: 2 mg/kg
  PRX-102 2 mg/kg every 2 weeks
  Intervention: Drug: PRX-102

Inclusion Criteria:

• Symptomatic adult Fabry patients (≥18 yrs)
• Males: plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than lower limit of normal (LLN in plasma=3.2 nmol/hr/ml, LLN in leucocytes=32 nmol/hr/mg/protein)
• Females: historical genetic test results consistent with Fabry mutations
• Globotriaosylceramide (Gb3) concentration in urine > 1.5 times upper normal limit
• Patients who have never received enzyme replacement therapy (ERT) in the past, or patients who have not received ERT in the past 6 months and have a negative anti alpha galactosidase antibody test
• Chronic kidney disease - stages 1 or 2 (CKD1 or 2) (Appendix 7) with proteinuria > 300 mg/g protein-to-creatinine ratio or equivalent, measured in a Spot urine sample, demonstrated in 2 separate samples (1 sample at screening visit and the other from historical data)
• The patient signs informed consent
• Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically acceptable method of contraception, not including the rhythm method

Exclusion Criteria:

• Participation in any trial of an investigational drug within 30 days prior to study screening
• Chronic kidney disease stages 3-5 (CKD 3-5) (Appendix 7)
• History of dialysis or renal transplantation
• Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening
• Severe myocardial fibrosis by MRI (≥2 late-enhancement [LE] positive left ventricular segments) (Weidemann et al. 2009)
• History of clinical stroke
• Pregnant or nursing
• Presence of HIV and/or HBsAg and/or Hepatitis C infections
• Known allergies to ERT
• Known allergy to Gadolinium based contrast agents
• Presence of any medical, emotional, behavioral or psychological condition that, in the judgment of the Investigator and/or Medical Director, would interfere with the patient's compliance with the requirements of the study