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

NCT03079063 | Completed Phase 3 DMC

• 1 other identifier: UGA2014-02
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

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.

Conditions

Factor VII Deficiency

Outcome Measures

Primary Outcomes (2)

• Area under the plasma activity-time curve from time 0 to last quantifiable activity (AUClast)

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

  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

• Maximum plasma concentration of the factor VII activity (Cmax).

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

  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 (11)

• Area under the plasma concentration-time curve from time 0 to infinity (AUCinf)

  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

• Time of Cmax (tmax)

  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)

  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 (λz)

  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

• Elimination half-life (t½)

  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

Study Arms (2)

Eptacog alfa biosimilar for PK

EXPERIMENTAL

Randomized, double-blind, single dose cross-over for PK, with 12 months follow up with eptacog alfa biosimilar provided for treatment of bleeding on demand - or - prophylaxis.

Biological: Eptacog alfa, biosimilar

Novoseven

ACTIVE COMPARATOR

Randomized, double-blind, single dose cross-over for PK, with 12 months follow up with eptacog alfa biosimilar provided for treatment of bleeding on demand - or - prophylaxis.

Biological: Novoseven

Interventions

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.

Eptacog alfa biosimilar for PK

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.

Novoseven

Eligibility Criteria

• Age: 12 Years - 65 Years
• Gender Eligibility Details: Male and female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AryoGen Pharmed Co.: lead

Study Sites (2)

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

Shiraz, Iran

Location

Comprehensive Hemophilia Care Center

Tehran, Iran

Location

MeSH Terms

Conditions

Factor VII Deficiency

Interventions

recombinant FVIIa; Biosimilar Pharmaceuticals

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Officials

• Massimo Iacobelli, MD

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinding is performed by an independent third party operator (nurse/pharmacist, unblinded), who will prepare undistinguishable syringes with patient's dosing and labeling. Central lab operators will be blinded.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, single dose, double blinded, two-way cross-over study.

Study Record Dates

• First Submitted: March 4, 2017
• First Posted: March 14, 2017
• Study Start: March 1, 2017
• Primary Completion: November 30, 2020
• Study Completion: January 28, 2021
• Last Updated: February 4, 2021

Record last verified: 2020-07

Locations

IR (2)