Clinical trial NCT04789954: Study on the Dose-response Relationship of Pharmacodynamic Parameters in Patients With Hemophilia With Inhibitors
Official title: An Exploratory Study to Evaluate the Dose Response-Relationship of Pharmacodynamic Parameters of AryoSeven, in Patients With Hemophilia With Inhibitors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Hemophilia A With Inhibitor
Hemophilia B With Inhibitor
Lead sponsor: AryoGen Pharmed Co.
Sponsor class: INDUSTRY
First posted: 2021-03-10
Enrollment: 14
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Lag time of the thrombin generation curve
timeFrame: Up to 30 hours after AryoSeven and NovoSeven injection
Secondary outcomes:
measure: Endogenous Thrombin Potential (PD parameter)
timeFrame: Up to 30 hours after AryoSeven and NovoSeven injection
measure: Time to Peak (PD parameter)
timeFrame: Up to 30 hours after AryoSeven and NovoSeven injection
measure: Peak height (PD parameter)
timeFrame: Up to 30 hours after AryoSeven and NovoSeven injection
measure: F1.2 prothrombin fragments (PD parameter)
timeFrame: Up to 30 hours after AryoSeven and NovoSeven injection
measure: D-dimer (PD parameter)
timeFrame: Up to 30 hours after AryoSeven and NovoSeven injection
measure: AUCinf (PK parameter)
timeFrame: Up to 30 hours after AryoSeven and NovoSeven injection
measure: Cmax (PK parameter)
timeFrame: Up to 30 hours after AryoSeven and NovoSeven injection
measure: Time of Cmax (PK parameter)
timeFrame: Up to 30 hours after AryoSeven and NovoSeven injection
Other outcomes:
Locations:
city: Teheran
country: Iran, Islamic Republic of
facility: Comprehensive Hemophilia Care Center
Study officials:
affiliation: Consultant
name: Massimo Iacobelli, MD
role: STUDY_DIRECTOR
References: