Switch Over Study of Biosimilar Agalsidase Beta for Fabry Disease

Phase III, Open-label, Switch Over Trial of the Efficacy and Safety of Agalsidase Beta Biosidus (AGA BETA BS) in Fabry Disease Patients Previously Stabilized With Fabrazyme®

BIO-AGA-Fase III-001 is a Phase III, prospective, multicenter, open-label, single-group, baseline-controlled, switch over clinical trial to evaluate the efficacy and safety of AGA BETA BS in patients with FD already treated and previously stabilized with Fabrazyme®.

BIO-AGA-Fase III-001 is a Phase III, prospective, multicenter, open-label, single-group, baseline-controlled, switch over clinical trial to evaluate the efficacy and safety of AGA BETA BS in patients with FD already treated and previously stabilized with Fabrazyme®.

The study will be conducted in 2 parts: a 5-week Lead-in period (period 1) and 54 week treatment period (period 2). During period 1 all participants will receive 2 intravenous (IV) infusions of Fabrazyme®, provided by Biosidus. After that, in period 2 all participants will switch treatment to AGA BETA BS.

A total of up to 20 participants are planned for the study.

•The primary objective of the study is to evaluate the equivalence in efficacy between AGA BETA BS and Fabrazyme® after 6 months of treatment in participants with Fabry disease previously stabilized with Fabrazyme, by measuring disease biomarker (mean serum Lyso-Gb3 marker ratio after 26 weeks of treatment, defined as serum level of the marker Lyso-Gb3 after 26 weeks (6 months) divided by serum level of the marker Lyso-Gb3 at baseline).

Inclusion Criteria:

Sex and Age

1. Male or female participant with ≥16 and ≤60 years of age at the time of signing the informed consent form (ICF).

   Reproduction

2. Female participants who are not pregnant, breastfeeding, donating eggs (ova, oocytes), or considering becoming pregnant during the study and for 3 months after the last dose of study treatment.

3. All women of childbearing potential (WOCBP) must have a negative urine pregnancy test at the Screening visit and at Baseline visit (prior to the first dose of experimental intervention).

4. WOCBP must use one highly effective form of birth control contraception through the study and for 3 months after the last dose of study treatment.

5. Male participants who are not considering fathering a child during the study and for 3 months after the last dose of study treatment.

6. Male sexually active participant with female partner(s) of childbearing potential must agree to use male condoms during the study and for 3 months after the last dose of study treatment or have documented successful surgical sterilization.

7. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

8. Confirmed previous diagnosis of FD.

   1. Women: preferably present genetic testing showing pathogenic GLA mutation consistent with FD at screening.
   2. Men: preferably present leukocyte α-Gal A activity below normal range and/ or pathogenic GLA mutation consistent with FD at screening.
   3. Male with classic FD phenotype, female with classic FD and men with late onset may be included.

9. Participants who have been on stable Fabrazyme® treatment for at least 6 months prior to Baseline visit.

10. Patients that in the last 3 months before the baseline visit have been receiving ≥80% of Fabrazyme®'s labeled dose/kg, this calculation includes both infusions provided by Biosidus during the Lead in period.

11. Disease status considered clinically stabilized, at Investigators' discretion.

12. Estimated glomerular filtration rate (eGFR) ≥45 mL/minute/1.73 m2 by CKD-EPI equation at Screening visit.

13. If receiving pain killers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), participants must be in a stable dose for ≥ 4 weeks.

Exclusion Criteria:

1. Chronic kidney disease in stage 3b, 4, or 5.
2. History of dialysis, kidney transplant or participants who are on the waiting list for a kidney transplant.
3. Proteinuria ≥1 g/day at screening.
4. Participants who have suffered a clinical cardiovascular event (such as but not limited to myocardial infarction, transient ischemic attack) within 6 months prior to
5. Participants who have clinically significant unstable cardiac disease (such as but not limited to uncontrolled symptomatic arrhythmia, unstable angina, congestive heart failure New York Heart Association class III or IV).
6. Participants who have suffered a clinical cerebrovascular event (such as but not limited to stroke, transient ischemic attack) within 6 months prior to Screening visit.
7. History of anaphylaxis or other type I hypersensitivity reactions to agalsidase beta.
8. History of acute kidney injury in the 12 months prior to Screening visit (such as but not limited to acute interstitial nephritis, acute renal failure of glomerular origin or caused by vasculitis).
9. Presence of any medical, emotional, behavioral, or psychological condition that, according to the Investigator, would interfere with the participant's compliance with the requirements of the study.
10. Treatment initiation or change of dose of ACE inhibitors or ARBs in the 4 weeks before the screening.
11. Current participation in an interventional study, in which the participant received any drug within 90 days before the Screening visit.