A Randomized, Two-Armed, Double-Blind, Single-Dose, Cross-Over, Bioequivalence Clinical Trial to Compare Pharmacokinetic Parameters and Safety of Recombinant Human Factor Viii With Fc Fusion Produced by Aryogen Pharmed Company Versus Elocta® (Reference Product) in Previously Treated Patients With Severe Haemophilia A

A Randomized, Two-Armed, Double-Blind, Single-Dose, Cross-Over, Bioequivalence Clinical Trial to Compare Pharmacokinetic Parameters and Safety of Recombinant Human Factor Viii With Fc Fusion Produced by Aryogen Pharmed Company Versus Elocta® (Reference Product) in Previously Treated Patients With Severe Haemophilia A Publisher

Eghbali A¹ ; Eshghi P² ; Toogeh G³ ; Alavi S² ; Badiei Z⁴ ; Ghanavat M⁵ ; Bordbar M⁶ ; Bazrafshan A⁷ ; Karimi K³ ; Ahmadinejad M⁸ ; Sabzvari A⁹ ; Kafi H¹⁰

Show Affiliations

1. Aliasghar Clinical Research Development Center, Iran University of Medical Sciences, Tehran, Iran
2. Pediatric Congenital Hematologic Disorders Research Center, Research Institute for Children’s Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3. Thrombosis Hemostasis Research Center, Tehran University of Medical Sciences, Tehran, Iran
4. Hemophilia and Thalassemia Center of Mashhad (Sarvar Clinic), Mashhad University of Medical Sciences, Mashhad, Iran
5. Isfahan University of Medical Sciences, Isfahan, Iran
6. Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
7. Hemophilia Center, Dastgheib Hospital, Shiraz, Iran
8. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
9. CinnaGen Medical Biotechnology Research Center, Alborz University of Medical Sciences, Karaj, Iran
10. Medical Department, Orchid Pharmed Company, Tehran, Iran

Source: Annals of Hematology Published:2025

Abstract

This clinical study evaluates the bioequivalence of recombinant factor VIII with Fc fusion protein (rFVIII-Fc) developed by AryoGen Pharmed Company compared to the reference product, Elocta® by Sobi Co., in severe haemophilia A patients. Fc-fused recombinant factor VIII represents a significant advancement in haemophilia A treatment, offering extended half-life and reduced infusion frequency, thus improving patients’ adherence to treatment and quality of life. In a randomized, double-blind, single-dose crossover trial, 50 Iranian patients were assigned to treatment groups in a 1:1 ratio. Subjects received both the test and the reference product with a 7-day washout period between treatments. Pharmacokinetic assessments were conducted over five days post-administration to evaluate the primary outcome, the dose-normalized area under the curve (DNAUC). The results established bioequivalence between rFVIII-Fc (AryoGen Pharmed Company) and Elocta®, based on the DNAUC as the primary outcome, in which the ratio of test and reference products was calculated to be 108.56 (90% confidence interval 104.88 to 112.37), falling within the pre-defined equivalence margin of 80–125%. Secondary outcomes, including area under the curve (AUCinf), maximum concentration (Cmax), and half-life, further supported bioequivalence. Safety profiles were comparable, with adverse events mainly related to haemophilia A rather than the intervention. In conclusion, the rFVIII-Fc product is bioequivalent to Elocta® with a similar safety profile, offering an effective alternative for severe haemophilia A patients. This trial was registered in ClinicalTrials.gov (NCT06137092). © The Author(s) 2025.

2. Cost-Effectiveness Analysis of Biogeneric Recombinant Activated Factor Vii (Aryoseven™) and Activated Prothrombin Complex Concentrates (Feiba™) to Treat Hemophilia a Patients With Inhibitors in Iran, Iranian Journal of Pharmaceutical Research (2016)

3. A Comparison of Efficacy Between Recombinant Activated Factor Vii (Aryoseven) and Novoseven in Patients With Hereditary Fviii Deficiency With Inhibitor, Clinical and Applied Thrombosis/Hemostasis (2016)

4. The Effect of the Dietary Approaches to Stop Hypertension (Dash) Diet on Body Composition, Complete Blood Count, Prothrombin Time, Inflammation and Liver Function in Haemophilic Adolescents, British Journal of Nutrition (2022)

5. Hepatitis C Virus Infection in Patients With Hemophilia in Isfahan, Iran, International Journal of Preventive Medicine (2012)

6. The First Discrete Choice Experiment on Usage of Bypassing Agents in Hemophilic Patients in Iran, Iranian Journal of Blood and Cancer (2016)

7. A Comparison Between Recombinant Activated Factor Vii (Aryoseven) and Novoseven in Patients With Congenital Factor Vii Deficiency, Clinical and Applied Thrombosis/Hemostasis (2015)

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Style	Citing Format
MLA	Eghbali A, et al.. "A Randomized, Two-Armed, Double-Blind, Single-Dose, Cross-Over, Bioequivalence Clinical Trial to Compare Pharmacokinetic Parameters and Safety of Recombinant Human Factor Viii With Fc Fusion Produced by Aryogen Pharmed Company Versus Elocta® (Reference Product) in Previously Treated Patients With Severe Haemophilia A." Annals of Hematology, vol. , no. , 2025, pp. -.
APA	Eghbali A, Eshghi P, Toogeh G, Alavi S, Badiei Z, Ghanavat M, Bordbar M, Bazrafshan A, Karimi K, Ahmadinejad M, Sabzvari A, Kafi H (2025). A Randomized, Two-Armed, Double-Blind, Single-Dose, Cross-Over, Bioequivalence Clinical Trial to Compare Pharmacokinetic Parameters and Safety of Recombinant Human Factor Viii With Fc Fusion Produced by Aryogen Pharmed Company Versus Elocta® (Reference Product) in Previously Treated Patients With Severe Haemophilia A. Annals of Hematology, (), -.
Chicago	Eghbali A, Eshghi P, Toogeh G, Alavi S, Badiei Z, Ghanavat M, Bordbar M, et al.. "A Randomized, Two-Armed, Double-Blind, Single-Dose, Cross-Over, Bioequivalence Clinical Trial to Compare Pharmacokinetic Parameters and Safety of Recombinant Human Factor Viii With Fc Fusion Produced by Aryogen Pharmed Company Versus Elocta® (Reference Product) in Previously Treated Patients With Severe Haemophilia A." Annals of Hematology , no. (2025): -.
Harvard	Eghbali A et al. (2025) 'A Randomized, Two-Armed, Double-Blind, Single-Dose, Cross-Over, Bioequivalence Clinical Trial to Compare Pharmacokinetic Parameters and Safety of Recombinant Human Factor Viii With Fc Fusion Produced by Aryogen Pharmed Company Versus Elocta® (Reference Product) in Previously Treated Patients With Severe Haemophilia A', Annals of Hematology, (), pp. -.
Vancouver	Eghbali A, Eshghi P, Toogeh G, Alavi S, Badiei Z, Ghanavat M, et al.. A Randomized, Two-Armed, Double-Blind, Single-Dose, Cross-Over, Bioequivalence Clinical Trial to Compare Pharmacokinetic Parameters and Safety of Recombinant Human Factor Viii With Fc Fusion Produced by Aryogen Pharmed Company Versus Elocta® (Reference Product) in Previously Treated Patients With Severe Haemophilia A. Annals of Hematology. 2025;():-.
BibTex	@article{ author = {Eghbali A and Eshghi P and Toogeh G and Alavi S and Badiei Z and Ghanavat M and Bordbar M and Bazrafshan A and Karimi K and Ahmadinejad M and Sabzvari A and Kafi H}, title = {A Randomized, Two-Armed, Double-Blind, Single-Dose, Cross-Over, Bioequivalence Clinical Trial to Compare Pharmacokinetic Parameters and Safety of Recombinant Human Factor Viii With Fc Fusion Produced by Aryogen Pharmed Company Versus Elocta® (Reference Product) in Previously Treated Patients With Severe Haemophilia A}, journal = {Annals of Hematology}, volume = {}, number = {}, pages = {-}, year = {2025} }
RIS	TY - JOUR AU - Eghbali A AU - Eshghi P AU - Toogeh G AU - Alavi S AU - Badiei Z AU - Ghanavat M AU - Bordbar M AU - Bazrafshan A AU - Karimi K AU - Ahmadinejad M AU - Sabzvari A AU - Kafi H TI - A Randomized, Two-Armed, Double-Blind, Single-Dose, Cross-Over, Bioequivalence Clinical Trial to Compare Pharmacokinetic Parameters and Safety of Recombinant Human Factor Viii With Fc Fusion Produced by Aryogen Pharmed Company Versus Elocta® (Reference Product) in Previously Treated Patients With Severe Haemophilia A JO - Annals of Hematology VL - IS - SP - EP - PY - 2025 ER -

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