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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Randomized, Multicenter, Single-dose, Cross-over, Double-blind Study Comparing the Pharmacokinetic of Biosimilar Eptacog Alfa With Novoseven®, in Patients With Congenital Fa

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.

Additional 26 patients with the same inclusions and exclusions criteria will be included in this study (for a total 50 patients). These patients will not enter the PK phase of the study but they will be followed to receive biosimilar eptacog alfa, on demand, for every bleeding episode that should occur during 12 months - or - for prophylaxis, with the aim of monitoring of inhibiting antibody formation, lack of efficacy and collection of safety data. The modality of treatment with biosimilar eptacog alfa (on demand or prophylaxis) will be decided by the Investigator.

Detailed Summary:
Sponsor: AryoGen Pharmed Co.

Current Primary Outcome:

• 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 ]
  Measurement of plasma level of factor VII clotting activity (FVII:C) [one-stage clotting method using recombinant tissue factor preparation (STA-Deficient and STA-Neoplastin R; Diagnostica Stago, France)],
• 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 ]
  Measurement of plasma level of factor VII clotting activity (FVII:C) [one-stage clotting method using recombinant tissue factor preparation (STA-Deficient and STA-Neoplastin R; Diagnostica Stago, France)],

Original Primary Outcome: Same as current

Current Secondary Outcome:

• 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 ]
  Measurement of plasma level of factor VII clotting activity (FVII:C) [one-stage clotting method using recombinant tissue factor preparation (STA-Deficient and STA-Neoplastin R; Diagnostica Stago, France)]
• 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 ]
  Measurement of plasma level of factor VII clotting activity (FVII:C) [one-stage clotting method using recombinant tissue factor preparation (STA-Deficient and STA-Neoplastin R; Diagnostica Stago, France)]
• 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 ]
  Measurement of plasma level of factor VII clotting activity (FVII:C) [one-stage clotting method using recombinant tissue factor preparation (STA-Deficient and STA-Neoplastin R; Diagnostica Stago, France)]
• First order rate constant associated with the terminal (log-linear) portion of the curve (λz) [ 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 ]
  Measurement of plasma level of factor VII clotting activity (FVII:C) [one-stage clotting method using recombinant tissue factor preparation (STA-Deficient and STA-Neoplastin R; Diagnostica Stago, France)]
• 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 ]
  Measurement of plasma level of factor VII clotting activity (FVII:C) [one-stage clotting method using recombinant tissue factor preparation (STA-Deficient and STA-Neoplastin R; Diagnostica Stago, France)]
• 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 ]
  Measurement of plasma level of factor VII clotting activity (FVII:C) [one-stage clotting method using recombinant tissue factor preparation (STA-Deficient and STA-Neoplastin R; Diagnostica Stago, France)]
• 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 ]
  Measurement of plasma level of factor VII clotting activity (FVII:C) [one-stage clotting method using recombinant tissue factor preparation (STA-Deficient and STA-Neoplastin R; Diagnostica Stago, France)]
• 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 ]
  Measurement of plasma level of factor VII clotting activity (FVII:C) [one-stage clotting method using recombinant tissue factor preparation (STA-Deficient and STA-Neoplastin R; Diagnostica Stago, France)]
• Clinical response in controlling acute bleeding. [ Time Frame: 2, 6 and 12 hours post infusion (last dose of Eptacog alfa Biosimilar) ]
  Rated by the treating physician using a 4 point scale (Excellent, Good, Moderate, None).
• 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. ]
  The modified Nijmegen method of the Bethesda assay
• Adverse Events [ Time Frame: Adverse events (AEs) will be monitored throughout the trial, from the first dose administered up to 12 months follow-up. ]

Original Secondary Outcome: Same as current

Information By: AryoGen Pharmed Co.

Dates:
Date Received: March 4, 2017
Date Started: March 1, 2017
Date Completion: November 2018
Last Updated: March 8, 2017
Last Verified: March 2017