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

February 3, 2021 updated by: AryoGen Pharmed Co.

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Iran, Islamic Republic of
      • Shiraz, Iran, Islamic Republic of
        • Hemophilia Center - Hematology & Oncology Dept. Shiraz University of Medical Science
      • Tehran, Iran, Islamic Republic of
        • Comprehensive Hemophilia Care Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Eptacog alfa biosimilar for PK
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
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.
Active Comparator: Novoseven
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
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)],
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).
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)],
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 Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)]
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)
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)]
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
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
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)]
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)
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)]
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
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)]
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
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
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)]
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)
Rated by the treating physician using a 4 point scale (Excellent, Good, Moderate, None).
2, 6 and 12 hours post infusion (last dose of Eptacog alfa Biosimilar)
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
On plasma samples obtained at screening visit, before the second dose/second drug administration, and then every 3 months for a year.
Adverse Events
Time Frame: Adverse events (AEs) will be monitored throughout the trial, from the first dose administered up to 12 months follow-up.
Adverse events (AEs) will be monitored throughout the trial, from the first dose administered up to 12 months follow-up.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AryoGen Pharmed Co.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Massimo Iacobelli, MD

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 28, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 4, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 8, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 14, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 4, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 3, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UGA2014-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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