PK/PD Study of 2 Agalsidase Formulations in Single Dose of 1 mg/kg Administered to Healthy Volunteers as IV Infusion
Primary Purpose
Fabry Disease
Status
Active
Phase
Phase 1
Locations
Argentina
Study Type
Interventional
Intervention
Agalsidase beta from Biosidus 1 mg/kg
Fabrazyme (agalsidase beta) 1 mg/kg
Sponsored by
About this trial
This is an interventional treatment trial for Fabry Disease focused on measuring Fabry Disease, agalsidase beta, phase 1
Eligibility Criteria
Inclusion Criteria:
- Male subjects between the ages of 18 and 40
- Body mass index (BMI) between 19 and 25 kg/m².
- 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.
- 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)
- Volunteers who are well disposed to the study and have signed the approved informed consent prior to the start of the study
Exclusion Criteria:
- History of clinically significant allergies (except for untreated asymptomatic seasonal allergies)
- 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
- Volunteers who are receiving other drugs (prescription or over-the-counter) or who have within the 2 weeks prior to the study
- Volunteers with history of autoimmune diseases.
- Chronic disorders of the CNS, psychological and/or psychiatric disorders: bipolar disorder, severe depression, insomnia, changes in personality
- Active or chronic infections
- Having received live or inactivated viral or bacterial vaccines, within the fifteen days prior to visits 1 or 2
- 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.
- Known allergies to any of the components of the formulations
- Active smoker, of more than 10 cigarettes/day
- Current clinical evidence of severe digestive disorders, surgeries of the gastrointestinal tract (except for appendectomy)
- Current clinical evidence of kidney disease
- Current clinical evidence of liver disorders
- Current clinical evidence of respiratory and cardiac disease
- Presence of diabetes mellitus, thyroid dysfunction or other endocrine disorders
- Evidence of active gastroduodenal disease
- History of peripheral thrombotic phenomena
- Underlying neurological disease
- Presence of a current progressive chronic disease
- History of drug or alcohol abuse or addiction within the last three years
- Participation in a clinical study within the last three months
- 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.
- 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.
- 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)
- Significant abnormalities in the electrocardiogram
- Positive PCR test for COVID-19
- Positive serology for HIV, hepatitis B or hepatitis C
- Abnormal clinical laboratory test results (that according to the principal investigator's judgement are considered clinically significant)
- Uncooperative volunteers
Sites / Locations
- Sanatorio Nuestra Señora del Pilar
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Agalsidase Beta from Biosidus
Fabrazyme (Sanofi-Genzyme)
Arm Description
Participants received a single infusion at a dose 1 mg/kg
Participants received a single infusion at a dose 1 mg/kg
Outcomes
Primary Outcome Measures
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")
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")
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")
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")
Secondary Outcome Measures
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.
Number of patients with adverse events
Evaluation of the product safety with analysis of incidence of adverse events and tolerance.
Immunogenicity of agalsidase beta
The titer of anti-agalsidase beta antibodies will be determined in both groups of volunteers, by biological activity neutralization method
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05343715
Brief Title
PK/PD Study of 2 Agalsidase Formulations in Single Dose of 1 mg/kg Administered to Healthy Volunteers as IV Infusion
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 23, 2021 (Actual)
Primary Completion Date
March 6, 2022 (Actual)
Study Completion Date
April 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bio Sidus SA
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fabry Disease
Keywords
Fabry Disease, agalsidase beta, phase 1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Agalsidase Beta from Biosidus
Arm Type
Experimental
Arm Description
Participants received a single infusion at a dose 1 mg/kg
Arm Title
Fabrazyme (Sanofi-Genzyme)
Arm Type
Active Comparator
Arm Description
Participants received a single infusion at a dose 1 mg/kg
Intervention Type
Biological
Intervention Name(s)
Agalsidase beta from Biosidus 1 mg/kg
Intervention Description
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
Intervention Type
Biological
Intervention Name(s)
Fabrazyme (agalsidase beta) 1 mg/kg
Intervention Description
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
Primary Outcome Measure Information:
Title
Maximum serum concentration of agalsidase beta (Cmax)
Description
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")
Time Frame
0, 1, 3, 5, 5.5, 6, 7, 8, 10 and 12 hours from the beginning of the infusion
Title
Area under the curve of serum concentration between times 0 and 12 hours of agalsidase beta
Description
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")
Time Frame
0, 1, 3, 5, 5.5, 6, 7, 8, 10 and 12 hours from the beginning of the infusion
Title
Time at which maximum serum concentration of agalsidase beta is observed (Tmax)
Description
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")
Time Frame
0, 1, 3, 5, 5.5, 6, 7, 8, 10 and 12 hours from the beginning of the infusion
Title
Area under the curve of serum concentration, resulting from the extrapolation from time 0 to infinite time
Description
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")
Time Frame
0, 1, 3, 5, 5.5, 6, 7, 8, 10 and 12 hours from the beginning of the infusion
Secondary Outcome Measure Information:
Title
Enzymatic Activity on plasma samples measured with fluorometric method
Description
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.
Time Frame
Pre-infusion and 5 hours post administration (end of infusion)
Title
Number of patients with adverse events
Description
Evaluation of the product safety with analysis of incidence of adverse events and tolerance.
Time Frame
From infusion to 35 days after
Title
Immunogenicity of agalsidase beta
Description
The titer of anti-agalsidase beta antibodies will be determined in both groups of volunteers, by biological activity neutralization method
Time Frame
0 and 12 hours after infusion
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Male subjects between the ages of 18 and 40
Body mass index (BMI) between 19 and 25 kg/m².
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.
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)
Volunteers who are well disposed to the study and have signed the approved informed consent prior to the start of the study
Exclusion Criteria:
History of clinically significant allergies (except for untreated asymptomatic seasonal allergies)
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
Volunteers who are receiving other drugs (prescription or over-the-counter) or who have within the 2 weeks prior to the study
Volunteers with history of autoimmune diseases.
Chronic disorders of the CNS, psychological and/or psychiatric disorders: bipolar disorder, severe depression, insomnia, changes in personality
Active or chronic infections
Having received live or inactivated viral or bacterial vaccines, within the fifteen days prior to visits 1 or 2
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.
Known allergies to any of the components of the formulations
Active smoker, of more than 10 cigarettes/day
Current clinical evidence of severe digestive disorders, surgeries of the gastrointestinal tract (except for appendectomy)
Current clinical evidence of kidney disease
Current clinical evidence of liver disorders
Current clinical evidence of respiratory and cardiac disease
Presence of diabetes mellitus, thyroid dysfunction or other endocrine disorders
Evidence of active gastroduodenal disease
History of peripheral thrombotic phenomena
Underlying neurological disease
Presence of a current progressive chronic disease
History of drug or alcohol abuse or addiction within the last three years
Participation in a clinical study within the last three months
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.
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.
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)
Significant abnormalities in the electrocardiogram
Positive PCR test for COVID-19
Positive serology for HIV, hepatitis B or hepatitis C
Abnormal clinical laboratory test results (that according to the principal investigator's judgement are considered clinically significant)
Uncooperative volunteers
Facility Information:
Facility Name
Sanatorio Nuestra Señora del Pilar
City
Ciudadela
State/Province
Buenos Aires
ZIP/Postal Code
1702
Country
Argentina
12. IPD Sharing Statement
Plan to Share IPD
No
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PK/PD Study of 2 Agalsidase Formulations in Single Dose of 1 mg/kg Administered to Healthy Volunteers as IV Infusion
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