Study on the Dose-response Relationship of Pharmacodynamic Parameters in Patients With Hemophilia With Inhibitors

Hemophilia A With Inhibitor Clinical Trial

Official title:

An Exploratory Study to Evaluate the Dose Response-Relationship of Pharmacodynamic Parameters of AryoSeven, in Patients With Hemophilia With Inhibitors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04789954
• Other study ID #: UGA 2020-01
• Status: Completed
• Phase: Early Phase 1
• Start date: December 29, 2020
• Est. completion date: July 31, 2022

Study information

• Verified date: September 2022
• Source: AryoGen Pharmed Co.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Randomized, double-blind, single-dose, 5 ways crossover, exploratory clinical trial evaluating four different doses of AryoSeven (eptacog alfa, activated) and NovoSeven on selected pharmacodynamic parameters in patients with hemophilia with inhibitors.

Description:

Randomized, double-blind, single dose, 5 ways crossover, clinical trial evaluating four different doses (10 µg/kg, 30 µg/kg, 90 µg/kg, and 270 µg/kg) of AryoSeven (recombinant human FVII activated or eptacog alfa, activated) and one dose of NovoSeven (30 µg/kg) on selected pharmacodynamic parameters (PD) [Primary: Thrombin Generation Assay (TGA)] in male adult and adolescent (>12 years) patients with hemophilia A or B, with an inhibitors titer >5 Bethesda Units [BU] and not in bleeding status. This will be an exploratory study to evaluate dose-response relationship of PD markers as surrogate efficacy endpoints.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: July 31, 2022
• Est. primary completion date: August 13, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of congenital haemophilia A or B with inhibitors to FVIII or FIX titer >5 Bethesda Units [BU]
• with > 2 episodes of bleeding/year requiring treatment with FVII infusions, not in bleeding episode
• Male adults and adolescents (>12 years)
• Patient informed consent has been obtained [Patients to be enrolled must also provide voluntary written informed consent to the protocol prior to screening to be eligible for the study. For adolescents, parent/legal guardian must provide consent and, wherever possible, patient assent will also be obtained. For compromised patients, their designated proxy must provide informed consent].
• Patients willing and able to be hospitalized prior to time of study medication administration for plasma sampling (5 times during the study).

Exclusion Criteria:

• Any other type of congenital or acquired coagulopathy, such as: liver disease (hepatitis), vitamin k deficiency, uremia, malignancy.
• Antibodies against Factor VII
• Ongoing bleeding prophylaxis regimens with AryoSeven/NovoSeven or planned to occur during the trial
• 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
• Factor VIII/IX immune tolerance induction regimen planned to occur during the trial
• 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.
• Concomitant diseases and/or medications, or any other conditions, that render the patient unsuitable for inclusion into the study in the judgement of the investigator.

Related Conditions & MeSH terms

• Hemophilia A
• Hemophilia A With Inhibitor
• Hemophilia B
• Hemophilia B With Inhibitor

Intervention

Biological:
• Eptacog alfa, activated
A dose sequence for each injection will be randomly selected from the following doses: 10 µg/kg, 30 µg/kg, 90 µg/kg, or 270 µg/kg, separated by a wash-out period of 3 days.

Locations

Country	Name	City	State
Iran, Islamic Republic of	Comprehensive Hemophilia Care Center	Teheran

Sponsors (1)

Lead Sponsor	Collaborator
AryoGen Pharmed Co.

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lag time of the thrombin generation curve	Time to 16.7% of peak plasmatic concentration, in minutes.	Up to 30 hours after AryoSeven and NovoSeven injection
Secondary	Endogenous Thrombin Potential (PD parameter)	Area under the curve plasma levels of thrombin generation curve (in nmol/per minute)	Up to 30 hours after AryoSeven and NovoSeven injection
Secondary	Time to Peak (PD parameter)	Time to Peak of thrombin generation curve (in minutes)	Up to 30 hours after AryoSeven and NovoSeven injection
Secondary	Peak height (PD parameter)	Peak height of thrombin generation curve (in nmol/ml)	Up to 30 hours after AryoSeven and NovoSeven injection
Secondary	F1.2 prothrombin fragments (PD parameter)	Peak height (micg/L)	Up to 30 hours after AryoSeven and NovoSeven injection
Secondary	D-dimer (PD parameter)	Peak height (micg/L)	Up to 30 hours after AryoSeven and NovoSeven injection
Secondary	AUCinf (PK parameter)	Area under the plasma concentration time curve from time 0 to infinity, based on the last observed concentration;	Up to 30 hours after AryoSeven and NovoSeven injection
Secondary	Cmax (PK parameter)	Observed maximum plasma concentration	Up to 30 hours after AryoSeven and NovoSeven injection
Secondary	Time of Cmax (PK parameter)	Time of observed maximum plasma concentration	Up to 30 hours after AryoSeven and NovoSeven injection