Safety, Efficacy, & PK of PRX-102 in Patients With Fabry Disease Administered Intravenously Every 4 Weeks
Condition: Fabry Disease
MeSH terms: Fabry Disease
Intervention: Pegunigalsidase alfa
Intervention description: Pegunigalsidase alfa 2 mg/kg every 4 weeks
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Switch over study in patients previously receiving either agalsidase alfa or agalsidase beta and switched to pegunigalsidase alfa (PRX-102) for the treatment of Fabry disease.
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Enzyme-Replacement Therapy; pegunigalsidase alfa; Fabry Disease

Summary:

      This open-label switchover study will assess the safety, efficacy, and pharmacokinetics of
      pegunigalsidase alfa (PRX-102) 2 mg/kg administered every 4 weeks for 52 weeks in Fabry
      patients previously treated with ERT: agalsidase alfa or agalsidase beta for at least 3
      years. Safety and efficacy exploratory endpoints will be evaluated throughout the study
      period and pharmacokinetics will be obtained on Day 1 and Week 52.
    

Eligibility criteria:

        Key inclusion criteria:

        Eligible subjects must fulfill the following 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 the laboratory reference ranges and one or
             more of the characteristic features of Fabry disease

               1. Neuropathic pain

               2. Cornea verticillata

               3. 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

               1. Neuropathic pain

               2. Cornea verticillata

               3. Clustered angiokeratoma

          5. Treatment with agalsidase alfa or agalsidase beta for at least 3 years and on a stable
             dose (>80% labelled dose/kg) for at least last 6 months

          6. eGFR ≥ 30 mL/min/1.73m^2 by CKD-EPI equation at screening visit

          7. Availability of at least 3 historical serum creatinine evaluations since starting
             agalsidase alfa or agalsidase beta treatment and not more than 2 years old

          8. Female patients and male patients whose co-partners are of child-bearing potential
             agree to use a medically accepted, highly effective method of contraception. These
             include combined (estrogen- and progestogen-containing) hormonal contraception
             associated with inhibition of ovulation (oral, intravaginal, or transdermal),
             progestogen-only hormonal contraception associated with inhibition of ovulation (oral,
             injectable, or implantable), intrauterine device (IUD), intrauterine hormone-releasing
             system (IUS), bilateral tubal occlusion, vasectomised partner, or sexual abstinence

          9. Patients whose clinical condition, in the opinion of the Investigator, is suitable for
             treatment with ERT every 4 weeks.

        Key exclusion criteria:

        The presence of any of the following excludes a subject from study enrollment:

          1. History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase alfa or
             agalsidase beta

          2. History of renal dialysis or transplantation

          3. Linear negative slope of eGFR of ≥ 2 mL/min/1.73m^2/year based on at least 4 serum
             creatinine values over approximately 2 years (including the value obtained at the
             screening visit)

          4. 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 post renal obstructive
             nephropathy)

          5. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)
             therapy initiated or dose changed in the 4 weeks prior to screening

          6. Urine protein to creatinine ratio (UPCR) at screening > 0.5 g/g or mg/mg or 500 mg/g
             and not treated with an ACE inhibitor or ARB

          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. Cerebrovascular event (stroke, transient ischemic attack) in the 6-month period before
             screening

         10. 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.