Safety and Efficacy of PRX-102 in Patients With Fabry Disease Currently Treated With REPLAGAL® (Agalsidase Alfa)
Condition: Fabry Disease
MeSH terms: Fabry Disease
Intervention: PRX-102 (pegunigalsidase alfa)
Intervention description: PRX-102 1 mg/kg every 2 weeks
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Fabry disease; Enzyme-Replacement Therapy; pegunigalsidase alfa; PRX-102; alpha galactosidase-A

Summary:

      This is an open label switch over study to assess the safety and efficacy of PRX-102
      (pegunigalsidase alfa). Patients treated with agalsidase alfa for at least 2 years and on a
      stable dose (>80% labelled dose/kg) for at least 6 months. Patients will be screened and
      evaluated over 3 months while continuing on agalsidase alfa. Following the screening period,
      the patient will be enrolled and switched from their agalsidase alfa treatment to receive
      intravenous (IV) infusions of PRX-102 1 mg/kg every two weeks for 12 months. No more than 25%
      of treated patients will be female.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age: 18-60 years

          2. A documented diagnosis of Fabry disease

          3. Males: plasma and/or leucocyte alpha galactosidase activity (by activity assay) less
             than lower limit of normal according to laboratory range and one or more of the
             characteristic features of Fabry disease i. Neuropathic pain ii. Cornea verticillata
             iii. Clustered angiokeratoma

          4. Females: historical genetic test results consistent with Fabry mutations, or in the
             case of novel mutations a first degree male relative with Fabry disease, and one or
             more of the characteristic features of Fabry disease i. Neuropathic pain ii. Cornea
             verticillata iii. Clustered angiokeratoma

          5. Treatment with agalsidase alfa for at least 2 years and on a stable dose (>80%
             labelled dose/kg) for at least 6 months

          6. eGFR ≥ 40 ml/min/1.73 m2 by CKD-EPI equation

          7. Availability of at least 2 historical serum creatinine evaluations since starting
             agalsidase alfa treatment and not more than 2 years

          8. 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:

          1. History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase alfa

          2. History of renal dialysis or transplantation

          3. History of acute kidney injury in the 12 months prior to screening, including specific
             kidney diseases (e.g., acute interstitial nephritis, acute glomerular and vasculitic
             renal diseases); non-specific conditions (e.g, ischemia, toxic injury); as well as
             extrarenal pathology (e.g., prerenal azotemia, and acute postrenal obstructive
             nephropathy)

          4. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)
             therapy initiated or dose changed in the 4 weeks prior to screening

          5. Urine protein to creatinine ratio (UPCR) > 0.5 g/g and not treated with an ACE
             inhibitor or ARB

          6. Known history of hypersensitivity to Gadolinium contrast agent that was not managed by
             the use of premedication;

          7. Females who are pregnant, planning to become pregnant during the study, or are breast
             feeding

          8. Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period
             before screening

          9. Congestive heart failure NYHA Class IV

         10. Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before
             screening

         11. Presence of any medical, emotional, behavioral or psychological condition that, in the
             judgment of the Investigator and/or Medical Monitor would interfere with the patient's
             compliance with the requirements of the study