The study is designed as a randomized, two-armed, double-blind, single-dose, crossover, two-sequence, active-controlled, multi-center, bioequivalence clinical trial with a primary endpoint of dose-normalized area under the curve (dnAUC last)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
50
rFVIII-Fc, IV, 50 units/kg/ single dose, cross-over
Seyed-Al-Shohada Hospital
Isfahan, Iran
Sarvar Clinic
Mashhad, Iran
Dastqeib Hospital
Shiraz, Iran
Imam Khomeini
Tehran, Iran
Mofid Hospital
Tehran, Iran
dose-normalized Area Under the Curve (dnAUC last)
Area under the concentration-time curve measured from the time of administration to the last measurable time point
Time frame: pre-dose, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 8 hours, 24 hours, 48 hours, 72 hours, 96 hours, 120 hours post-dose
Area Under the Curve to Infinity (AUC inf)
Area under the concentration-time curve measured from the time of administration to the infinity.
Time frame: pre-dose, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 8 hours, 24 hours, 48 hours, 72 hours, 96 hours, 120 hours post-dose
Maximum Plasma Activity (Cmax)
Maximum plasma activity during a dosing interval
Time frame: pre-dose, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 8 hours, 24 hours, 48 hours, 72 hours, 96 hours, 120 hours post-dose
Incremental Recovery (IR)
The rise in FVIII activity in IU/dL per unit dose administered in IU/kg
Time frame: pre-dose, 15 minutes, 30 minutes, 1 hour
Half-life (T ½)
Time required for the activity of the drug to reach half of its original value
Time frame: pre-dose, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 8 hours, 24 hours, 48 hours, 72 hours, 96 hours, 120 hours post-dose
Volume of distribution (Vd)
Volume of distribution estimated from the terminal phase
Time frame: pre-dose, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 8 hours, 24 hours, 48 hours, 72 hours, 96 hours, 120 hours post-dose
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Clearance (Cl)
Rate at which the body removes the drug, measured as the volume of the plasma cleared of drug per unit time per unit weight
Time frame: pre-dose, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 8 hours, 24 hours, 48 hours, 72 hours, 96 hours, 120 hours post-dose
Safety assessment by evaluation of adverse events (AEs) and abnormal laboratory results
Safety assessment, including the incidence of all reported AEs and abnormal laboratory results was done. All AEs were classified based on the Medical Dictionary for Regulatory Activities (MedDRA Desktop Browser 4.0 Beta) terms as System Organ Class (SOC) and Preferred Term (PT). All the reported events were graded according to the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Moreover, seriousness of AEs was assessed according to International Council for Harmonization (ICH-E2B) guidelines. The causality relation was assessed based on the World Health Organization (WHO) criteria.
Time frame: Adverse events collection and documentation was done during the study (up to 28 days)
Immunogenicity assessment
Immunogenicity of factor viii was evaluated at scheduled visits by blood sampling to determine the production of inhibitor against factor viii.
Time frame: Immunogenicity sampling was done at screening visit and day 7, 12 and 28