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NCT Number: NCT03079063

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

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.

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Key information

Conditions

Factor VII Deficiency Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Coagulation Protein Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders

Age range

12 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hemophilia Center - Hematology & Oncology Dept. Shiraz University of Medical Science, Shiraz, Iran

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Eptacog alfa, biosimilar

Biological

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. Then, in an open follow up phase of 12 months, for every bleeding episode eptacog alfa biosimilar 30 μg/kg, on demand, for one of more days until resolution of bleeding, based on the Investigator's decision - or - prophylaxis with eptacog alfa biosimilar, with dose, frequency, and duration of treatment based on the Investigator's decision. The modality of treatment (on demand or prophylaxis) will be decided by the Investigator.

Novoseven

Biological

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.

Primary outcomes

  1. 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)],

  2. 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)],

Secondary outcomes

  1. 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)]

  2. 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)]

  3. 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)]

  4. 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)]

  5. 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)]

  6. 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)]

  7. 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)]

  8. 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)]

  9. 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).

  10. 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

  11. Adverse Events

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

Sponsors and collaborators

Lead sponsor

AryoGen Pharmed Co.

Industry

Registry information

Official study 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

Important dates

Study start
2017
Primary completion
2020
Study completion
2021
First posted
Mar 14, 2017
Registry last updated
Feb 4, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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