Evaluate the Safety and Efficacy of Fabagal® (Agalsidase Beta) in Patients With Fabry Disease

A Phase 3 Randomized, Double-blinded, Active-controlled, Multicenter Trial to Evaluate the Safety and Efficacy of Fabagal® (Agalsidase Beta) in Patients With Fabry Disease

Evaluate the safety and efficacy of Fabagal® developed by ISU ABXIS Co., Ltd., which has similar efficacy to active comparator (Agalsidase beta).

The primary objective is to evaluate the efficacy of Fabagal compared to active comparator (Agalsidase beta). The secondary objectives will evaluate the safety, pharmacokinetics, and immunogenicity of Fabagal compared to active comparator (Agalsidase beta).

Inclusion Criteria:

1. Those who have been diagnosed with Fabry disease by genetic and alpha-galactosidase A enzyme tests and grouped by sex are as follows:

   • Male: Those who have confirmed GLA mutation (variation of α-galactosidase A gene) by genetic testing, and whose activity of alpha-galactosidase A in leukocytes is 5% or less than the normal mean value
   • Female: Those who have confirmed GLA mutation by genetic testing, and whose alpha-galactosidase A is within the normal range or is deficient

2. Age: Those who are aged 8 years or older

3. Those who have at least one of the following symptoms and signs:

   • Glomerular filtration rate decreased (Inclusion criteria: 2 or more cases of 30 ≦ eGFR < 90 mL/min/1.73 m2 [adjusted for age >40] [including results within 6 months of the screening visit, but including results within 12 months for patients with a 60 ≦ eGFR < 90 mL/min/1.73 m2])

     • Proteinuria that is equivalent to microalbuminuria or worse (Inclusion criteria: 2 or more cases of creatinine 30 mg/g in random urine at least 24 hours apart [including results within 6 months of the screening visit] or ≥30 mg of albuminuria in 24-hour urine)

       • For 24 hr urinary protein extraction (>4 mg/m2/hr) or for spot urinary protein/creatinine ratio (≥200 mg/g [Cr]) *Pediatrics: Aged <19 years

         • Abnormal left ventricular function as evidenced by MRI or echocardiography

           • Left ventricular mass index (LVMI)* >115 g/m2 (male), >95 g/m2 (female) or

           • Left ventricular wall thickness >12 mm (However, in the case of patients with hypertension, patients must have blood pressure treatment for at least 6 months prior to administration of the same drug) etc.

             • Clinically significant arrhythmias and conduction disturbances, etc.

               • Stroke or transient ischemic attack, etc., as evidenced by objective testing

4. Patients who have not previously received enzyme replacement therapy (ERT) or Chaperone therapy for treatment of Fabry disease

5. Patients who voluntarily consented and signed the informed consent form

6. Patients (female patients and partners of male patients who are of childbearing potential) who have agreed to use a medically appropriate method of contraception (intrauterine device, condoms, surgical methods such as vasectomy) during the clinical study

Exclusion Criteria:

1. Patients who participated in other studies in which investigational products are administered within 30 days prior to the screening visit
2. Patients with chronic kidney disease stage 4 to 5 (CKD 4-5; see Section 16.1)
3. Patients who are currently on dialysis or have a history of kidney transplantation, or patients scheduled for dialysis at the time of screening, or waitlisted for kidney transplantation
4. Patients who have started angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) treatment within 4 weeks prior to the screening visit or whose dose has been changed
5. Patients who are pregnant, breastfeeding, or planning to become pregnant or breastfeed during the clinical study
6. Patients with a history of HIV, hepatitis B/C or HIV antibodies, hepatitis B surface antigens, or hepatitis C antibodies
7. Patient whose medical, emotional, behavioral, or psychological conditions appear to interfere with compliance with the requirements of the clinical study according to the investigator's judgment