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

NCT ID: NCT04789954

Last Updated: 2022-09-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-29
• Study Completion Date: 2022-07-31

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.

Conditions

Hemophilia A With Inhibitor; Hemophilia B With Inhibitor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

AryoSeven 10 μg/kg

Single dose, intravenously

Group Type: EXPERIMENTAL

Eptacog alfa, activated

Intervention Type: BIOLOGICAL

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.

AryoSeven 30 μg/kg

Single dose, intravenously

Group Type: EXPERIMENTAL

Eptacog alfa, activated

Intervention Type: BIOLOGICAL

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.

AryoSeven 90 μg/kg

Single dose, intravenously

Group Type: EXPERIMENTAL

Eptacog alfa, activated

Intervention Type: BIOLOGICAL

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.

AryoSeven 270 μg/kg

Single dose, intravenously

Group Type: EXPERIMENTAL

Eptacog alfa, activated

Intervention Type: BIOLOGICAL

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.

NovoSeven 30 μg/kg

Single dose, intravenously

Group Type: ACTIVE_COMPARATOR

Eptacog alfa, activated

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 12 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

AryoGen Pharmed Co.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Massimo Iacobelli, MD

Role: STUDY_DIRECTOR

Consultant

Locations

Comprehensive Hemophilia Care Center

Tehran, , Iran

Countries

Iran

Other Identifiers

UGA 2020-01

Identifier Type: -

Identifier Source: org_study_id