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

Severe Hemophilia A Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06137092
• Other study ID #: FVIII.ARY.AE.00.PK
• Status: Completed
• Phase: Phase 3
• Start date: July 22, 2023
• Est. completion date: September 27, 2023

Study information

• Verified date: October 2023
• Source: AryoGen Pharmed Co.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: September 27, 2023
• Est. primary completion date: September 27, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Hemophilia A
• Severe Hemophilia A

Intervention

Drug:
• Factor VIII, recombinant human with Fc fusion (rFVIII-Fc)
rFVIII-Fc, IV, 50 units/kg/ single dose, cross-over

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AryoGen Pharmed Co.

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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