Clinical trial NCT06137092: rFVIII-Fc (Produced by AryoGen Pharmed Co.) Pharmacokinetic Study
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Severe Hemophilia A
Lead sponsor: AryoGen Pharmed Co.
Sponsor class: INDUSTRY
First posted: 2023-11-18
Enrollment: 50
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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)


Eligibility criteria: 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)

Primary outcomes:
measure: dose-normalized Area Under the Curve (dnAUC last)
timeFrame: 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 outcomes:
measure: Area Under the Curve to Infinity (AUC inf)
timeFrame: 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
measure: Maximum Plasma Activity (Cmax)
timeFrame: 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
measure: Incremental Recovery (IR)
timeFrame: pre-dose, 15 minutes, 30 minutes, 1 hour
measure: Half-life (T ½)
timeFrame: 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
measure: Volume of distribution (Vd)
timeFrame: 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
measure: Clearance (Cl)
timeFrame: 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
measure: Safety assessment by evaluation of adverse events (AEs) and abnormal laboratory results
timeFrame: Adverse events collection and documentation was done during the study (up to 28 days)
measure: Immunogenicity assessment
timeFrame: Immunogenicity sampling was done at screening visit and day 7, 12 and 28
Other outcomes:
Locations:
city: Isfahan
country: Iran, Islamic Republic of
facility: Seyed-Al-Shohada Hospital
city: Mashhad
country: Iran, Islamic Republic of
facility: Sarvar Clinic
city: Shiraz
country: Iran, Islamic Republic of
facility: Dastqeib Hospital
city: Tehran
country: Iran, Islamic Republic of
facility: Imam Khomeini
city: Tehran
country: Iran, Islamic Republic of
facility: Mofid Hospital
Study officials:
affiliation: Iran University of Medical Sciences
name: Aziz Eghbali, Assoc. Prof.
role: PRINCIPAL_INVESTIGATOR
References: