Severe Hemophilia A
Conditions
Brief summary
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)
Interventions
DRUGFactor VIII, recombinant human with Fc fusion (rFVIII-Fc)
rFVIII-Fc, IV, 50 units/kg/ single dose, cross-over
Sponsors
AryoGen Pharmed Co.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male patients ≥ 12 years, with signed informed consent by the patient, or the patient's legally authorized representative for patients under the legal age * Diagnosed with severe hemophilia A (endogenous FVIII \<1% \[1 IU/dL\]) * History of at least 150 documented prior exposure days to any FVIII product * Having adequate bone marrow and organ function: * Plt ≥ 80,000 cells/µL * Hb ≥ 8 mg/dL * eGFR ≥ 30 mL/min * ALT or AST ≤ 5×ULN * Serum bilirubin ≤ 1.5×ULN
Exclusion criteria
* Measurable anti-drug antibody activity against FVIII (≥ 0.6 BU/mL) at screening or a history of developing anti FVIII antibody * History of other coagulation disorders except for hemophilia A * Acute hemorrhagic state * Infection with HCV or HBV * HIV-positive patients * Infusion of any products containing FVIII within 7 days prior to first administration * Previous treatment with commercially available extended half-life FVIII products * Receiving drugs which increase bleeding tendency (e.g: Anti-coagulants, antiplatelets, omega 3, Vit E, etc.) within 2 weeks of screening. NSAIDs are permitted. * Current systemic treatment with immunosuppressive drugs * Hypersensitivity or anaphylaxis associated with any FVIII concentrate or intravenous immunoglobulin (IVIG) * Planned elective surgery * Current enrolment or willing to enroll in any other experimental study during the time of current trial * Subjects assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol (e.g.: physical, psychological and mental problems)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| dose-normalized Area Under the Curve (dnAUC last) | 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 concentration-time curve measured from the time of administration to the last measurable time point |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Activity (Cmax) | 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 during a dosing interval |
| Incremental Recovery (IR) | pre-dose, 15 minutes, 30 minutes, 1 hour | The rise in FVIII activity in IU/dL per unit dose administered in IU/kg |
| Half-life (T ½) | 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 | Time required for the activity of the drug to reach half of its original value |
| Area Under the Curve to Infinity (AUC inf) | 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 concentration-time curve measured from the time of administration to the infinity. |
| Clearance (Cl) | 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 | Rate at which the body removes the drug, measured as the volume of the plasma cleared of drug per unit time per unit weight |
| Safety assessment by evaluation of adverse events (AEs) and abnormal laboratory results | Adverse events collection and documentation was done during the study (up to 28 days) | 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. |
| Immunogenicity assessment | Immunogenicity sampling was done at screening visit and day 7, 12 and 28 | Immunogenicity of factor viii was evaluated at scheduled visits by blood sampling to determine the production of inhibitor against factor viii. |
| Volume of distribution (Vd) | 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 estimated from the terminal phase |
Countries
Iran
Outcome results
None listed