rFVIII-Fc (Produced by AryoGen Pharmed Co.) Pharmacokinetic Study

A Randomized, Two-armed, Double-blind, Single-dose, Crossover, Two-sequence, Bioequivalence Clinical Trial to Compare PK Parameters and Safety of rFVIII-Fc (AryoGen Pharmed Co.) Versus Elocta® in PTPs With Severe Hemophilia A

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 Overview

• Status: Completed
• Conditions: Severe Hemophilia A
• Intervention / Treatment: Drug: Factor VIII, recombinant human with Fc fusion (rFVIII-Fc)

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Isfahan, Iran, Islamic Republic of
    • Seyed-Al-Shohada Hospital
  • Mashhad, Iran, Islamic Republic of
    • Sarvar Clinic
  • Shiraz, Iran, Islamic Republic of
    • Dastqeib Hospital
  • Tehran, Iran, Islamic Republic of
    • Imam Khomeini
  • Tehran, Iran, Islamic Republic of
    • Mofid Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AryoGen Pharmed Co. rFVIII-Fc/Elocta® (Sobi Co. rFVIII-Fc); AryoGen Pharmed Co. rFVIII-Fc, IV, 50 units/kg, single dose, then Elocta® (Sobi Co. rFVIII-Fc), IV, 50 units/kg, single dose (cross-over)	Drug: Factor VIII, recombinant human with Fc fusion (rFVIII-Fc); rFVIII-Fc, IV, 50 units/kg/ single dose, cross-over
Experimental: Elocta® (Sobi Co. rFVIII-Fc)/AryoGen Pharmed Co. rFVIII-Fc; Elocta® (Sobi Co. rFVIII-Fc), IV, 50 units/kg, single dose, then AryoGen Pharmed Co. rFVIII-Fc, IV, 50 units/kg, single dose (cross-over)	Drug: Factor VIII, recombinant human with Fc fusion (rFVIII-Fc); rFVIII-Fc, IV, 50 units/kg/ single dose, cross-over

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve to Infinity (AUC inf)	Area under the concentration-time curve measured from the time of administration to the infinity.	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	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	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	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	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
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	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.	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.	Immunogenicity sampling was done at screening visit and day 7, 12 and 28

Collaborators and Investigators

• Sponsor: AryoGen Pharmed Co.
• Investigators: Principal Investigator: Aziz Eghbali, Assoc. Prof., Iran University of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2023
• Primary Completion (Actual): September 27, 2023
• Study Completion (Actual): September 27, 2023

Study Registration Dates

• First Submitted: October 30, 2023
• First Submitted That Met QC Criteria: November 13, 2023
• First Posted (Estimated): November 17, 2023

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A; Coagulants; Factor VIII
• Other Study ID Numbers: FVIII.ARY.AE.00.PK

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No