PK/PD Study of 2 Agalsidase Formulations in Single Dose of 1 mg/kg Administered to Healthy Volunteers as IV Infusion

Comparative Pharmacokinetic and Pharmacodynamic Study Between 2 Agalsidase Beta Formulations at a Single Dose of 1 mg/kg of Agalsidase (Biosidus) and Fabrazyme (Sanofi Genzyme) as Intravenous Infusion in Male Healthy Volunteers

Pharmacokinetic/Pharmacodynamic Study of 2 agalsidase beta Formulations in Single Dose Administered to Healthy Volunteers as intravenous infusion, at a concentration of 1 mg/kg

Study Overview

• Status: Completed
• Conditions: Fabry Disease
• Intervention / Treatment: Biological: Agalsidase beta from Biosidus 1 mg/kg; Biological: Fabrazyme (agalsidase beta) 1 mg/kg

Detailed Description

Volunteers will receive either one or the other agalsidase beta formulation. Drug will be administered as an intravenous 5h infusion. Plasma samples will be taken at different time points, from before infusion up to 12h later. Pharmacokinetic (PK) and pharmacodynamic (PD) profile will be determined, and bioequivalence evaluated.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Ciudadela, Buenos Aires, Argentina, 1702
      • Sanatorio Nuestra Señora del Pilar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 36 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male subjects between the ages of 18 and 40
2. Body mass index (BMI) between 19 and 25 kg/m².
3. Volunteers whose complementary exams (ECG, chest X-ray, blood and urine, PCR for COVID-19), performed prior to their inclusion are within the normal range and/or are not clinically significant according to the investigator's judgement.
4. Subjects with systolic blood pressure higher than 110 mmHg and lower than 139 mmHg, diastolic blood pressure higher than 70 mmHg and lower than 89 mmHg with a heart rate higher than 50 and lower than 90 beats per minute after being seated for 5 minutes and, then, standing up (extreme values are included)
5. Volunteers who are well disposed to the study and have signed the approved informed consent prior to the start of the study

Exclusion Criteria:

1. History of clinically significant allergies (except for untreated asymptomatic seasonal allergies)
2. A drop of ≥ 20 mmHg of systolic blood pressure or ≥ 10 mmHg of diastolic blood pressure within the first 3 minutes after the postural change
3. Volunteers who are receiving other drugs (prescription or over-the-counter) or who have within the 2 weeks prior to the study
4. Volunteers with history of autoimmune diseases.
5. Chronic disorders of the CNS, psychological and/or psychiatric disorders: bipolar disorder, severe depression, insomnia, changes in personality
6. Active or chronic infections
7. Having received live or inactivated viral or bacterial vaccines, within the fifteen days prior to visits 1 or 2
8. For COVID vaccines, a 15 day window period prior to visits #1 or #2 must be respected. This period was taken from the recommendations published by the National Ministry of Health on May 29th 2021. The volunteer will be able to receive the vaccine 35 days after receiving the investigational product.
9. Known allergies to any of the components of the formulations
10. Active smoker, of more than 10 cigarettes/day
11. Current clinical evidence of severe digestive disorders, surgeries of the gastrointestinal tract (except for appendectomy)
12. Current clinical evidence of kidney disease
13. Current clinical evidence of liver disorders
14. Current clinical evidence of respiratory and cardiac disease
15. Presence of diabetes mellitus, thyroid dysfunction or other endocrine disorders
16. Evidence of active gastroduodenal disease
17. History of peripheral thrombotic phenomena
18. Underlying neurological disease
19. Presence of a current progressive chronic disease
20. History of drug or alcohol abuse or addiction within the last three years
21. Participation in a clinical study within the last three months
22. Use of any drug within the fourteen days prior to the start of the study that, according to the principal investigator's judgement may interfere with the biodistribution of the medicinal product.
23. Subjects who have donated or suffered from blood loss within the twelve weeks prior to the start of the study, or intends to donate blood within the following three months after the completion of the study.
24. Excessive drinker of tea, cocoa, mate, coffee and/or caffeinated drinks (>5 cups/day) or of wine (>0.5 L/day) or alcohol (>50 ml/day)
25. Significant abnormalities in the electrocardiogram
26. Positive PCR test for COVID-19
27. Positive serology for HIV, hepatitis B or hepatitis C
28. Abnormal clinical laboratory test results (that according to the principal investigator's judgement are considered clinically significant)
29. Uncooperative volunteers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Agalsidase Beta from Biosidus; Participants received a single infusion at a dose 1 mg/kg	Biological: Agalsidase beta from Biosidus 1 mg/kg; Patients received an infusion of 1 mg/kg of Agalsidase Beta from Biosidus. Final infusion dose is achieved with lyophilized drug at concentration 35 mg and 5 mg
Active Comparator: Fabrazyme (Sanofi-Genzyme); Participants received a single infusion at a dose 1 mg/kg	Biological: Fabrazyme (agalsidase beta) 1 mg/kg; Patients received an infusion of 1 mg/kg of Fabrazyme. Final infusion dose is achieved with lyophilized drug at concentration 35 mg and 5 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Serum Concentration of Agalsidase Beta (Cmax)	Compare the maximum serum concentration of two formulations of agalsidase beta after intravenous infusion of 1 mg/kg: Fabrazyme (Sanofi-Genzyme) (Reference Formulation, "R"); Agalsidase beta from Biosidus SA (Test Formulation, "T")	0, 1, 3, 5, 5.5, 6, 7, 8, 10 and 12 hours from the beginning of the infusion
Area Under the Curve of Serum Concentration Between Times 0 and 12 Hours of Agalsidase Beta	Compare the area under the curve between times 0 and 12 hours of two formulations of agalsidase beta after intravenous infusion of 1 mg/kg: Fabrazyme (Sanofi-Genzyme) (Reference Formulation, "R"); Agalsidase beta from Biosidus SA (Test Formulation, "T")	0, 1, 3, 5, 5.5, 6, 7, 8, 10 and 12 hours from the beginning of the infusion
Time at Which Maximum Serum Concentration of Agalsidase Beta is Observed (Tmax)	Compare the time at which maximum serum concentration of agalsidase beta is observed of two formulations of agalsidase beta after intravenous infusion of 1 mg/kg: Fabrazyme (Sanofi-Genzyme) (Reference Formulation, "R"); Agalsidase beta from Biosidus SA (Test Formulation, "T")	0, 1, 3, 5, 5.5, 6, 7, 8, 10 and 12 hours from the beginning of the infusion
Area Under the Curve of Serum Concentration, Resulting From the Extrapolation From Time 0 to Infinite Time	Compare the area under the curve of serum concentration, resulting from the extrapolation from time 0 to infinite time of two formulations of agalsidase beta after intravenous infusion of 1 mg/kg: Fabrazyme (Sanofi-Genzyme) (Reference Formulation, "R"); Agalsidase beta from Biosidus SA (Test Formulation, "T")	0, 1, 3, 5, 5.5, 6, 7, 8, 10 and 12 hours from the beginning of the infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Enzymatic Activity on Plasma Samples Measured With Fluorometric Method	Comparison between enzymatic activity of both formulations of agalsidase beta, assessing the difference between the 5 hour timepoint and the basal determination, to estimate their biological activity as part of the pharmacodynamic analysis. A fluorometric assay will be used. The enzymatic activity will be measured in mU/ml. The variation of enzymatic activity between the sample taken at the end of the infusion (5 hours) and pre-infusion will be analyzed.	Pre-infusion and 5 hours post administration (end of infusion)
Number of Patients With Adverse Events	Evaluation of the product safety with analysis of incidence of adverse events and tolerance.	From infusion to 35 days after
Number of Participants With Positive Results for the Presence of Neutralizing Antibodies Against Agalsidase Beta	The presence of neutralizing antibodies to agalsidase beta activity was analyzed in serum samples from 24 volunteers (0h, 12h and 35 days), by biological activity neutralization method. The percentage of inhibition in the samples was calculated by comparing the activity value of 1 ng of agalsidase beta alone with that of agalsidase treated with the serum samples. Those samples with percentage inhibition >50% were defined as positive.	0 hours,12 hours and 35 days after the end of the infusion.

Collaborators and Investigators

• Sponsor: Bio Sidus SA
• Investigators: Principal Investigator: Eduardo Pirotzky, MD, Sanatorio Nuestra Señora del Pilar

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2021
• Primary Completion (Actual): March 6, 2022
• Study Completion (Actual): April 17, 2022

Study Registration Dates

• First Submitted: January 24, 2022
• First Submitted That Met QC Criteria: April 18, 2022
• First Posted (Actual): April 25, 2022

Study Record Updates

• Last Update Posted (Estimated): October 15, 2025
• Last Update Submitted That Met QC Criteria: October 2, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: phase 1; Fabry Disease; agalsidase beta
• 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: AGA Biosidus

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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