Switch Over Study of Biosimilar Agalsidase Beta for Fabry Disease (SMILE)

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®.

Study Overview

• Status: Completed
• Conditions: Fabry Disease
• Intervention / Treatment: Drug: Recombinant human alpha galactosidase A (agalsidase beta); Drug: Recombinant human alpha-galactosidase A (agalsidase beta)

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Instituto de Investigaciones Clinicas Quilmes
  • Córdoba, Argentina, X5004
    • Clinica Universitaria Reina Fabiola
  • La Rioja, Argentina, F5300
    • Centro Oncologico Riojano Integral
  • Buenos Aires
    • Pergamino, Buenos Aires, Argentina, 2700
      • Instituto de Nefrología Pergamino S.R.L
    • San Isidro, Buenos Aires, Argentina, 1642
      • Centro Médico Santa María de la Salud

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Fabrazyme® then AGA BETA BS; The study has a single-arm. First, all participants will receive 2 doses of Fabrazyme® with approximately 14 days between them, and afterwards all participants will switch treatment and receive AGA BETA BS for 54 weeks

Drug: Recombinant human alpha galactosidase A (agalsidase beta); All participants will receive 2 doses of Fabrazyme® with approximately 14 days between them. The dose will be 1 mg/kg of body mass every 2 weeks; Other Names: Fabrazyme; Drug: Recombinant human alpha-galactosidase A (agalsidase beta); All participants will receive AGA BETA BS for 54 weeks. The dose will be 1 mg/kg of body mass every 2 weeks; Other Names: AGA BETA BS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Lyso Gb3 Serum Levels	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. Endpoint: 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.	Baseline (after 5 week lead-in period on Fabrazyme®) and 26 weeks (after the switch to AGA BETA BS)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Lyso-Gb3 Serum Levels	To evaluate the difference in efficacy between AGA BETA BS and Fabrazyme® after 1 year (54 weeks) of treatment in participants with Fabry disease previously stabilized with Fabrazyme®, by measuring disease biomarker. Endpoint: Mean serum Lyso-Gb3 marker ratio after 54 weeks of treatment, defined as serum level of the marker Lyso-Gb3 after 54 weeks (12 months) divided by serum level of the marker Lyso-Gb3 at baseline.	Baseline (after 5 week lead-in period on Fabrazyme®) and 54 weeks (after the switch to AGA BETA BS)
Change From Baseline in Pain Severity as Assessed by Brief Pain Inventory-short Form Pain Severity Items Scores	To compare the pain severity before and after the treatment with AGA BETA BS in participants with Fabry disease previously stabilized with Fabrazyme®, as measured by the Brief Pain Inventory-short form (BPI). The Brief Pain Inventory (BPI) is a validated patient-reported outcome instrument assessing pain severity and pain-related interference with daily activities. Pain severity is assessed using four items rated on a 0-10 numeric rating scale (0 = no pain; 10 = pain as bad as imaginable), with the score calculated as the mean of items (range 0-10; higher scores indicate worse pain). Pain interference is assessed using seven items rated on a 0-10 numeric rating scale (0 = does not interfere; 10 = completely interferes), with the score calculated as the mean of items (range 0-10; higher scores indicate worse outcome). Endpoint: Change from baseline in pain severity as assessed by BPI-short form pain severity items scores after 26 and 54 weeks of treatment.	Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS).
Change From Baseline in Pain Interference as Assessed by BPI-short Form Pain Interference Items Scores	To compare the impact of pain on daily functions before and after the treatment with AGA BETA BS in participants with Fabry disease previously stabilized with Fabrazyme®, as measured by the BPI (Brief Pain Inventory)-short form. The Brief Pain Inventory (BPI) is a validated patient-reported outcome instrument assessing pain severity and pain-related interference with daily activities. Pain severity is assessed using four items rated on a 0-10 numeric rating scale (0 = no pain; 10 = pain as bad as imaginable), with the score calculated as the mean of items (range 0-10; higher scores indicate worse pain). Pain interference is assessed using seven items rated on a 0-10 numeric rating scale (0 = does not interfere; 10 = completely interferes), with the score calculated as the mean of items (range 0-10; higher scores indicate worse outcome). Endpoint: Change from baseline in pain severity as assessed by BPI-short form pain severity items scores after 26 and 54 weeks of treatment.	Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS).
Change From Baseline in SF-36 Health Survey Scores	To compare the participants' perception of their own health before and after the treatment with AGA BETA BS in participants with Fabry disease previously stabilized with Fabrazyme®, as measured by the Short Form-36 Health Survey (SF-36). The Short Form-36 Health Survey (SF-36) is a validated patient-reported outcome instrument consisting of 36 questions designed to assess health-related quality of life. The questionnaire generates scores across eight domains (physical functioning, role limitations due to physical health, pain, general health, energy/fatigue, social functioning, role limitations due to emotional problems, and emotional well being), each scored on a 0-100 scale. Domain scores are calculated according to standard scoring algorithms, with higher scores indicating better health status and quality of life. Endpoint: Change from baseline in SF-36 scores after 26 and 54 weeks of treatment.	Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS).
Mean Blood Urea Nitrogen (BUN) Levels at Specified Timepoints		Baseline (after 5 week lead-in period on Fabrazyme®), 14 weeks, 26 weeks and 54 weeks (after the switch to AGA BETA BS).
Mean Estimated Glomerular Filtration Rate (eGFR) at Specified Timepoints		Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS).
Mean Urine Albumin-to-Creatinine Ratio at Specified Timepoints		Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS).
Mean Electrolyte and Phosphate Levels at Specified Timepoints		Baseline (after 5 week lead-in period on Fabrazyme®), 14 weeks, 26 weeks and 54 weeks (after the switch to AGA BETA BS).
Mean Heart Rate From Electrocardiogram Assessments at Specified Timepoints	Evaluation of Heart Rate based on the analysis of electrocardiogram exams performed at baseline, 26 weeks and 54 weeks.	Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS).
Mean PR, QRS, QT, QTcB, and QTcF Intervals at Specified Timepoints	Evaluation of PR, QRS, QT , QTcB and QTcF intervals based on the analysis of electrocardiogram exams performed at baseline, 26 weeks and 54 weeks.	Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS).
Mean Left Ventricular Wall Thickness at Specified Timepoints	Evaluation of cardiac function based on the analysis of bidimensional echocardiogram exams performed at baseline, 26 weeks and 54 weeks.	Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS).
Mean Left Ventricular Mass Index at Specified Timepoints	Evaluation of cardiac function based on the analysis of bidimensional echocardiogram exams performed at baseline, 26 weeks and 54 weeks.	Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS).
Mean Left Ventricular Ejection Fraction at Specified Timepoints	Evaluation of cardiac function based on the analysis of bidimensional echocardiogram exams performed at baseline, 26 weeks and 54 weeks.	Baseline (after 5 week lead-in period on Fabrazyme®), 26 weeks and 54 weeks (after the switch to AGA BETA BS).
Number of Participants With Positive Neutralizing Antibodies at Specified Timepoints	Count of participants whose serum samples showed a neutralization percentage of agalsidase beta activity greater than 50%, the predefined threshold indicating a positive result for neutralizing antibodies. Neutralizing antibody activity was evaluated using blood samples collected at Baseline, Week 14, Week 26, and Week 54. Participants with neutralization values exceeding the 50% cutoff were classified as positive for neutralizing antibodies at each timepoint.	Baseline (after 5 week lead-in period on Fabrazyme®),14 weeks, 26 weeks and 54 weeks (after the switch to AGA BETA BS).

Collaborators and Investigators

• Sponsor: Bio Sidus SA
• Collaborators: IQVIA RDS Inc.; IQVIA Solutions; Amsterdam UMC
• Investigators: Principal Investigator: Alberto A Fernández, MD, Instituto de Investigaciones Clinicas Quilmes

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2022
• Primary Completion (Actual): September 19, 2024
• Study Completion (Actual): March 31, 2025

Study Registration Dates

• First Submitted: November 28, 2022
• First Submitted That Met QC Criteria: April 24, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: January 30, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Fabry; Biosimilar; Fabry disease; agalsidase beta; Switch over
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lipid Metabolism Disorders; Genetic Diseases, X-Linked; Lysosomal Storage Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Sphingolipidoses; Lipidoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Fabry Disease; agalsidase beta
• Other Study ID Numbers: BIO-AGA-Fase III-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No