Study Comparing the Pharmacokinetic of Biosimilar Eptacog Alfa With Novoseven®, in Patients With Congenital Factor VII Deficiency

• Register: ClinicalTrials.gov
• Last refreshed on: 16 February 2021
• Main ID: NCT03079063
• Date of registration: 04/03/2017
• Prospective Registration: No
• Primary sponsor: AryoGen Pharmed Co.
• Public title: Study Comparing the Pharmacokinetic of Biosimilar Eptacog Alfa With Novoseven®, in Patients With Congenital Factor VII Deficiency
• Scientific 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
• Date of first enrolment: March 1, 2017
• Target sample size: 24
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03079063
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Iran, Islamic Republic of

Contacts

• Name: Massimo Iacobelli, MD

Key inclusion & exclusion 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.



Age minimum: 12 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Factor VII Deficiency

Intervention(s)

Biological: Eptacog alfa, biosimilar

Biological: Novoseven

Primary Outcome(s)

Maximum plasma concentration of the factor VII activity (Cmax). [Time Frame: 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]

Area under the plasma activity-time curve from time 0 to last quantifiable activity (AUClast) [Time Frame: 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 Outcome(s)

Adverse Events [Time Frame: Adverse events (AEs) will be monitored throughout the trial, from the first dose administered up to 12 months follow-up.]

Elimination half-life (t½) [Time Frame: 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]

Volume of distribution (Vss) [Time Frame: 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]

Clinical response in controlling acute bleeding. [Time Frame: 2, 6 and 12 hours post infusion (last dose of Eptacog alfa Biosimilar)]

Mean residence time (MRT) [Time Frame: 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]

Fraction of the total AUCinf that was derived by extrapolation beyond tlast (AUCextra) [Time Frame: 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]

First order rate constant associated with the terminal (log-linear) portion of the curve (?z) [Time Frame: 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]

Immunogenicity [Time Frame: On plasma samples obtained at screening visit, before the second dose/second drug administration, and then every 3 months for a year.]

Time of Cmax (tmax) [Time Frame: 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]

Area under the plasma concentration-time curve from time 0 to infinity (AUCinf) [Time Frame: 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]

Clearance (CL) [Time Frame: 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 ID(s)

UGA2014-02

Source(s) of Monetary Support

Please refer to primary and secondary sponsors