A Randomized, Multi-center, Single Dose, Cross over Study Comparing the Pharmacokinetic of Bio-similar EPTACOG Alfa with NOVOSEVEN®, in Patients with Congenital Factor VII Deficiency
Multicentre, randomized, single dose, double blinded, two-way cross-over study, evaluating the pharmacokinetic of biosimilar eptacog alfa (AryoSeven) and NovoSeven (Novo Nordisk) in adult and children (>12 years) patients with a confirmed diagnosis of severe Factor VII Deficiency (FVII <1%), with > 2 episodes of bleeding/year requiring treatment with FVII infusions. Screened patients will be enrolled if the results of anti-Factor VII antibodies assessed by the study center lab will be negative. Patients enrolled, not bleeding, will be randomized to receive both a single dose of AryoSeven 30 µg/kg and one single dose of NovoSeven 30 µg/kg, or vice versa, with doses separated by a washout period of 2 weeks. At the end of this phase, all patients will be followed for 12 months for monitoring of inhibiting antibody formation, lack of efficacy and collection of safety data to test. An additional group of patients, not entering the PK study, will be followed for Immunogenicity study only. These patients will be treated with AryoSeven 30 µg/kg for one of more days until resolution of bleeding, based on the Investigator’s decision, for every bleeding episode that should occur during 12 months. Plasma sampling for determination of antibody formation will be taken every 3 months. Patients in prophylaxis with AryoSeven (Iran) will stop prophylactic treatment 1 week before starting the trial (receiving first dose of study medication), Patients will be hospitalized at time of study medication administration and plasma sampling.
General information
Acronym
IRCT registration information
IRCT registration number:IRCT2016120231193N1
Registration date:2016-12-25, 1395/10/05
Registration timing:registered_while_recruiting
Last update:
Update count:2
Registration date
2016-12-25, 1395/10/05
Registrant information
Name
Amirhossein Saadatirad
Name of organization / entity
AryoGen Pharmed
Country
Iran (Islamic Republic of)
Phone
+98 26 3610 6480
Email address
saadatirada@aryogen.com
Recruitment status
Recruitment complete
Funding source
Aryogen Pharmed Company
Expected recruitment start date
2016-12-21, 1395/10/01
Expected recruitment end date
2017-09-23, 1396/07/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
A Randomized, Multi-center, Single Dose, Cross over Study Comparing the Pharmacokinetic of Bio-similar EPTACOG Alfa with NOVOSEVEN®, in Patients with Congenital Factor VII Deficiency
Public title
A Randomized, Multi-center, Single Dose, Cross over Study Comparing the Pharmacokinetic of Bio-similar EPTACOG Alfa with NOVOSEVEN®, in Patients with Congenital Factor VII Deficiency
Purpose
Health service research
Inclusion/Exclusion criteria
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; non in bleeding episode. Patients enrolled for the immunogenicity study only will be enrolled when in a bleeding episode.
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; platelet count less than 100.000 platelets/mcL (at screening visit); 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; ongoing bleeding prophylaxis regimens or planned to occur during the trial: Prophylaxis with AryoSeven (in Iran) is allowed with patients requested to stop prophylactic regime 1 week before starting the trial (receiving first dose of study medication); 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.
Age
From 12 years old to 99 years old
Gender
Both
Phase
3
Groups that have been masked
No information
Sample size
Target sample size:
50
Randomization (investigator's opinion)
Randomized
Randomization description
Blinding (investigator's opinion)
Double blinded
Blinding description
Placebo
Not used
Assignment
Crossover
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Iran University of Medical science
Street address
Iran University of Medical Sciences ,Shahid Hemmat Highway
City
Tehran
Postal code
1449614535
Approval date
2016-09-25, 1395/07/04
Ethics committee reference number
IR.IUMS.REC.1395.28155
2
Ethics committee
Name of ethics committee
Added at 2017-01-07: Shiraz University of Medical Sciences
Street address
Added at 2017-01-07: Shiraz University of Medical Sciences
City
Added at 2017-01-07: Shiraz
Postal code
Added at 2017-01-07:
Approval date
2016-12-14, 1395/09/24
Ethics committee reference number
Added at 2017-01-07: IR.SUMS.REC.1395.158
Health conditions studied
1
Description of health condition studied
Hereditary deficiency of factor VII
ICD-10 code
D68.2
ICD-10 code description
Hereditary deficiency of other clotting factors
Primary outcomes
1
Description
PK-parameters: the area under the plasma activity-time curve from time 0 to last quantifiable activity (AUClast) and maximum plasma activity Cmax
Timepoint
10 min, 20 min, 1 h, 3 h, 6 h, 8 h and 12 h and 24 h after AryoSeven or NovoSeven injection.
Method of measurement
Measurement of plasma level of factor VII clotting activity (FVII:C) performed by a central lab.
Secondary outcomes
1
Description
Secondary Pharmacokinetic parameters.
Timepoint
10 min, 20 min, 1 h, 3 h, 6 h, 8 h and 12 h and 24 h after AryoSeven or NovoSeven injection.
Method of measurement
Measurement of plasma level of factor VII clotting activity (FVII:C) performed by a central lab.
2
Description
Immunogenicity assessment.
Timepoint
At screening visit, after the second dose/second drug administration (visit 3) and then every 3 months for a year.
Method of measurement
The modified Nijmegen method of the Bethesda assay.
3
Description
Clinical response in treatment of bleeding
Timepoint
Every bleeding
Method of measurement
4 point scale (Excellent, Good, Moderate, None)
4
Description
Adverse events
Timepoint
at any time during the study
Method of measurement
Adverse events grading for severity, seriousness, expected or unexpected, relationship to the study drug, action taken, outcome.
Intervention groups
1
Description
AryoGen eptacog alfa (AryoSeven), intravenous, single dose of 30 µg/kg
Category
Treatment - Drugs
2
Description
Novo Nordisk eptacog alfa (Novoseven), intravenous, single dose of 30 µg/kg
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Iran Comprehensive Hemophilia Care Center
Full name of responsible person
Dr. Mohammadreza Baghaipour
Street address
Tehran, No. 3, N Felestin St
City
Tehran
2
Recruitment center
Name of recruitment center
Rasool Akram Hospital
Full name of responsible person
Dr. Mohammad Faranoush
Street address
Sattar Khan St, Niayesh ave
City
Tehran
3
Recruitment center
Name of recruitment center
Added at 2017-01-07: Hematology research center
Full name of responsible person
Added at 2017-01-07: Dr. Mohammad Reza Bordbar
Street address
Added at 2017-01-07: Khalili street-Mohammad Rasoul allah research building-6th floor-Hematology research center
City
Added at 2017-01-07: Shiraz
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
AryoGen Pharmed
Full name of responsible person
Amrhossein Saadatirad
Street address
No 140, Corner of Tajbakhsh street, 24th Km of Tehran Karaj Makhsous road
City
Tehran
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
AryoGen Pharmed
Proportion provided by this source
100
Public or private sector
empty
Domestic or foreign origin
empty
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
empty
Person responsible for general inquiries
Contact
Name of organization / entity
AryoGen Pharmed
Full name of responsible person
Amirhossein Saadatirad
Position
PhD
Other areas of specialty/work
Street address
No 140, corner of Tajbakhsh street, 24th Km of Tehran Karaj Makhsous road
City
Tehran
Postal code
3164819711
Phone
+98 21 3610 6480
Fax
Email
saadatirada@aryogen.com
Web page address
Person responsible for scientific inquiries
Contact
Name of organization / entity
Baqiyatallah Hospital
Full name of responsible person
Dr. Hasan Abolghasemi
Position
Full professor
Other areas of specialty/work
Street address
Mollasadra str, south Sheykh Bahaii str, Tehran
City
Tehran
Postal code
Phone
+98 218882742
Fax
Email
Abolghasem@bmsu.ac.ir
Web page address
Person responsible for updating data
Contact
Name of organization / entity
AryoGen Pharmed
Full name of responsible person
Amirhossein Saadatirad
Position
PhD
Other areas of specialty/work
Street address
No 140, corner of Tajbakhsh street, 24th Km of Tehran Karaj Makhsous road
City
Tehran
Postal code
Phone
+98 21 3610 6480
Fax
Email
Web page address
Sharing plan
Deidentified Individual Participant Data Set (IPD)