Clinical trial NCT05343715: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Fabry Disease
Keywords: Fabry Disease
agalsidase beta
phase 1
Lead sponsor: Bio Sidus SA
Sponsor class: INDUSTRY
First posted: 2022-04-25
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum Serum Concentration of Agalsidase Beta (Cmax)
timeFrame: 0, 1, 3, 5, 5.5, 6, 7, 8, 10 and 12 hours from the beginning of the infusion
measure: Area Under the Curve of Serum Concentration Between Times 0 and 12 Hours of Agalsidase Beta
timeFrame: 0, 1, 3, 5, 5.5, 6, 7, 8, 10 and 12 hours from the beginning of the infusion
measure: Time at Which Maximum Serum Concentration of Agalsidase Beta is Observed (Tmax)
timeFrame: 0, 1, 3, 5, 5.5, 6, 7, 8, 10 and 12 hours from the beginning of the infusion
measure: Area Under the Curve of Serum Concentration, Resulting From the Extrapolation From Time 0 to Infinite Time
timeFrame: 0, 1, 3, 5, 5.5, 6, 7, 8, 10 and 12 hours from the beginning of the infusion
Secondary outcomes:
measure: Enzymatic Activity on Plasma Samples Measured With Fluorometric Method
timeFrame: Pre-infusion and 5 hours post administration (end of infusion)
measure: Number of Patients With Adverse Events
timeFrame: From infusion to 35 days after
measure: Immunogenicity of Agalsidase Beta
timeFrame: 0 hours,12 hours and 35 days after the end of the infusion.
Other outcomes:
Locations:
city: Ciudadela
country: Argentina
facility: Sanatorio Nuestra Señora del Pilar
state: Buenos Aires
Study officials:
affiliation: Sanatorio Nuestra Señora del Pilar
name: Eduardo Pirotzky, MD
role: PRINCIPAL_INVESTIGATOR
References: