Factor VII DeficiencyPhase 3NCT03079063
Study Comparing the Pharmacokinetic of Biosimilar Eptacog Alfa With Novoseven®, in Patients With Congenital Factor VII Deficiency
A Phase 3 study testing Eptacog alfa, biosimilar and Novoseven in people with Factor VII Deficiency, run by AryoGen Pharmed Co. at 2 sites in Iran.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 to 65 years
- Conditions the study is for
- Factor VII Deficiency
- What is being tested?
- Eptacog alfa, biosimilar and Novoseven
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesIran
- Study dates
- 1 Mar 2017to 28 Jan 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 12Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
Iran2 sites
Hemophilia Center - Hematology & Oncology Dept. Shiraz University of Medical Science
Shiraz
Comprehensive Hemophilia Care Center
Tehran
About this study
Official 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
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
- Being tested
- Eptacog alfa, biosimilar, Novoseven
- Medical subject headings
- Factor VII Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eptacog alfa, biosimilarBiological
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.
NovosevenBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: Novoseven |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)],
Measured: 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)],
Measured: 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)
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)]
Measured: 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)
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)]
Measured: 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)
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)]
Measured: 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)
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)]
Measured: 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)
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)]
Measured: 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)
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)]
Measured: 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)
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)]
Measured: 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)
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)]
Measured: 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.
Rated by the treating physician using a 4 point scale (Excellent, Good, Moderate, None).
Measured: 2, 6 and 12 hours post infusion (last dose of Eptacog alfa Biosimilar)
Immunogenicity
The modified Nijmegen method of the Bethesda assay
Measured: On plasma samples obtained at screening visit, before the second dose/second drug administration, and then every 3 months for a year.
Adverse Events
Measured: Adverse events (AEs) will be monitored throughout the trial, from the first dose administered up to 12 months follow-up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2017
- Study start1 Mar 2017
- Primary completion30 Nov 2020
- Study completion28 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Factor VII DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized, single dose, double blinded, two-way cross-over study.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- AryoGen Pharmed Co.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Massimo Iacobelli, MD, Study director
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03079063
- Sponsor's protocol ID
- UGA2014-02
- Status last verified
- Jul 2020
- First submitted
- 4 Mar 2017
- Last updated
- 4 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03079063
- Acronym / sponsor ID
- UGA2014-02
- Conditions
- Factor VII Deficiency
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- AryoGen Pharmed Co.Industry (pharma, biotech, devices)
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- 30 Nov 2020 (actual)
- Study completion
- 28 Jan 2021 (actual)
- First posted
- 14 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, single dose, double blinded, two-way cross-over study.
| Arm | Type | Receives |
|---|---|---|
| Eptacog alfa biosimilar for PK | Experimental | Biological: Eptacog alfa, biosimilarRandomized, 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. |
| Novoseven | Active comparator | Biological: NovosevenRandomized, 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. |
Who may qualify
- Ages
- 12 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eptacog alfa, biosimilarEither 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. | Biological | Eptacog alfa biosimilar for PK |
| NovosevenEither 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. | Biological | Novoseven |
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)],
11 secondary outcomes
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
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
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 (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
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
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
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
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)
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.
Adverse Events
Time frame: Adverse events (AEs) will be monitored throughout the trial, from the first dose administered up to 12 months follow-up.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Massimo Iacobelli, MD study director
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Eptacog alfa, biosimilar and Novoseven in people with Factor VII Deficiency, run by AryoGen Pharmed Co. at 2 sites in Iran.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Iran. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2021.