Clinical trial NCT03079063: Study Comparing the Pharmacokinetic of Biosimilar Eptacog Alfa With Novoseven®, in Patients With Congenital Factor VII Deficiency
Official title: Randomized, Multicenter, Single-dose, Cross-over, Double-blind Study Comparing the Pharmacokinetic of Biosimilar Eptacog Alfa With Novoseven®, in Patients With Congenital Factor VII Deficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Factor VII Deficiency
Lead sponsor: AryoGen Pharmed Co.
Sponsor class: INDUSTRY
First posted: 2017-03-14
Enrollment: 24
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized, single dose, double blinded, two-way cross-over study.
Primary purpose: TREATMENT

Brief summary: The purpose of this multicentre, randomized, double blinded, single dose, two-way cross-over study, is to compare the pharmacokinetics (PK) of biosimilar eptacog alfa (activated) with Novoseven in 24 patients, adult and children (\>12 years), not bleeding, with inherited coagulation factor VII (FVII) deficiency (FVII \<1%). Patients will be randomized to receive either a single dose of eptacog alfa biosimilar 30 μg/kg and one single dose of NovoSeven 30 μg/kg, or vice versa, with doses separated by a washout period. All patients will be followed 12 months and will receive biosimilar eptacog alfa, on demand, for every bleeding episode that should occur - or - for prophylaxis, with the aim of monitoring of inhibiting antibody formation, lack of efficacy and collection of safety data.


Eligibility criteria: Inclusion Criteria:

* Patients with a confirmed diagnosis of congenital, severe Factor VII deficiency (FVII \<1%), with \> 2 episodes of bleeding/year requiring treatment with FVII infusions, in non bleeding status.
* Patients for the Additional group for immunogenicity should be enrolled when in a bleeding episode requiring treatment with FVII.
* Male and female subjects
* Adult and children (\>12 years)
* Written informed consent. For minor patients, parent/legal guardian will provide consent and, when possible, patient assent will also be obtained. For compromised patients their designated proxy must provide informed consent.

Exclusion Criteria:

* Any other type of congenital or acquired coagulopathy (except congenital Factor VII deficiency), such as: liver disease (hepatitis), vitamin k deficiency, uremia, malignancy.
* Antibodies against Factor VII
* Patients entering the PK Study Group who have not suspended prophylactic regimen with Novoseven or AryoSeven (biosimilar eptacog alfa) 3 days before starting the trial (receiving first dose of study medication).
* Patients entering the Additional Group for Immunogenicity study, only, who have been exposed to AryoSeven before starting study \[patients who have received Novoseven (on demand or in prophylaxis) before starting study are allowed\]
* Platelet count less than 100.000 platelets/μl (at screening visit)
* Patients who have received routine (prophylactic) treatment with rFVIIa in the period between screening visit (visit 1) and visit 2 of this study (first dose administration)
* Any clinical sign or known history of arterial thrombotic event or deep venous- thrombosis or pulmonary embolism
* HIV positive with current CD4+ count of less than 200/μl
* Liver Cirrhosis
* Known hypersensitivity to the study medication
* Parallel participation in another experimental drug trial.
* Parallel participation in another marketed drug trial that may affect the primary end point of the study.

Primary outcomes:
measure: Area under the plasma activity-time curve from time 0 to last quantifiable activity (AUClast)
timeFrame: Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase
measure: Maximum plasma concentration of the factor VII activity (Cmax).
timeFrame: Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase
Secondary outcomes:
measure: Area under the plasma concentration-time curve from time 0 to infinity (AUCinf)
timeFrame: Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase
measure: Time of Cmax (tmax)
timeFrame: Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase
measure: Fraction of the total AUCinf that was derived by extrapolation beyond tlast (AUCextra)
timeFrame: Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase
measure: First order rate constant associated with the terminal (log-linear) portion of the curve (λz)
timeFrame: Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase
measure: Elimination half-life (t½)
timeFrame: Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase
measure: Mean residence time (MRT)
timeFrame: Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase
measure: Clearance (CL)
timeFrame: Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase
measure: Volume of distribution (Vss)
timeFrame: Ten min before injection and 10 min, 20 min, 1h, 3h, 6h, 8h, 12h, 24h and 30h after injection, for both drug administered in the PK phase
measure: Clinical response in controlling acute bleeding.
timeFrame: 2, 6 and 12 hours post infusion (last dose of Eptacog alfa Biosimilar)
measure: Immunogenicity
timeFrame: On plasma samples obtained at screening visit, before the second dose/second drug administration, and then every 3 months for a year.
measure: Adverse Events
timeFrame: Adverse events (AEs) will be monitored throughout the trial, from the first dose administered up to 12 months follow-up.
Other outcomes:
Locations:
city: Shiraz
country: Iran, Islamic Republic of
facility: Hemophilia Center - Hematology & Oncology Dept. Shiraz University of Medical Science
city: Tehran
country: Iran, Islamic Republic of
facility: Comprehensive Hemophilia Care Center
Study officials:
name: Massimo Iacobelli, MD
role: STUDY_DIRECTOR
References: