Study of the Safety and Efficacy of PRX-102 Compared to Agalsidase Beta on Renal Function
Condition: Fabry Disease
MeSH terms: Fabry Disease
Intervention: PRX-102 (pegunigalsidase alfa); agalsidase beta
Intervention description: PRX-102 1 mg/kg every 2 weeks; agalsidase beta 1 mg/kg every 2 weeks
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 78.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Glomerular filtration rate; Proteinuria; PRX-102; pegunigalsidase alfa; Fabry Disease

Summary:

      This was a randomized, double-blind, active control study of the enzyme replacement therapy
      (ERT) drug PRX-102 (pegunigalsidase alfa) in Fabry disease patients with impaired renal
      function. Patients who had been treated for approximately 1 year with agalsidase beta and who
      had been on a stable dose of that product for at least 6 months were randomized in a 2:1
      ratio to either switch to PRX-102 or to continue treatment with agalsidase beta. Both
      treatments were delivered by intravenous infusions every two weeks, at a dosage of 1 mg/kg.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Symptomatic adult Fabry disease patients, age 18-60 years

               1. Males: Plasma and/or leucocyte alpha galactosidase activity (by activity assay)
                  less than 30% mean normal levels and one or more of the characteristic features
                  of Fabry disease

                  i. neuropathic pain

                  ii. cornea verticillata

                  iii. clustered angiokeratoma

               2. Females:

                  a. historical genetic test results consistent with Fabry pathogenic mutation and
                  one or more of the described characteristic features of Fabry disease:

                  i. neuropathic pain

                  ii. cornea verticillata

                  iii. clustered angiokeratoma

                  b. or in the case of novel mutations a first degree male family member with Fabry
                  disease with the same mutation, and one or more of the characteristic features of
                  Fabry disease

                  i. neuropathic pain

                  ii. cornea verticillata

                  iii. clustered angiokeratoma

          -  Screening eGFR by CKD-EPI equation 40 to 120 mL/min/1.73 m²

          -  Linear negative slope of eGFR based on at least 3 serum creatinine values over
             approximately 1 year (range of 9 to 18 months, including the value obtained at the
             screening visit) of ≥ 2 mL/min/1.73 m²/year

          -  Treatment with a dose of 1 mg/kg agalsidase beta per infusion every 2 weeks for at
             least one year and at least 80% of 13 (10.4) mg/kg total dose over the last 6 months.

          -  Female patients and male patients whose co-partners are of child-bearing potential
             agree to use a medically accepted method of contraception, not including the rhythm
             method.

        Exclusion Criteria:

          -  History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase beta

          -  Known non-pathogenic Fabry mutations

          -  History of renal dialysis or transplantation

          -  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)

          -  Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)
             therapy initiated or dose changed in the 4 weeks prior to screening

          -  Patient with a screening eGFR value between 91-120 mL/min/1.73 m², having an
             historical eGFR value higher than 120 mL/min/1.73 m² (during 9 to 18 months before
             screening)

          -  Urine protein to creatinine ratio (UPCR) > 0.5 g/g and not treated with an ACE
             inhibitor or ARB

          -  Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period
             before randomization

          -  Congestive heart failure NYHA Class IV

          -  Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before
             randomization

          -  Known history of hypersensitivity to Gadolinium contrast agent that is not managed by
             the use of pre-medication

          -  Female subjects who are pregnant, planning to become pregnant during the study, or are
             breastfeeding

          -  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