The Study of Dose Response Relationship Evaluation of AryoSeven in Hemophilia Patients

Phase 2

• Conditions: Condition 1: Congenital Hemophilia A with inhibitors. Condition 2: Congenital Hemophilia B with inhibitors.; Hereditary factor VIII deficiency; Hereditary factor IX deficiency

• Registration Number: IRCT20161202031193N3
• Lead Sponsor: AryoGen Pharmed

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 22 February 2021

Recruitment & Eligibility

• Status: Complete
• Sex: Male
• Target Recruitment: 12

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, non in bleeding episode
Male adult and adolescents (>12 years)
Patients 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 judgment of the investigator.

Study & Design

• Study Type: interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary Pharmacodynamic Parameter: TGA. Timepoint: 10 min prior to dose administration and at 10 min, 20 min, 1 h, 3 h, 5 h, 8 h, 12 h, 24 h and 30 h after AryoSeven or NovoSeven injection. Method of measurement: Thrombin Generation will be measured using the ST-Genesia® Thrombin Generation System (Diagnostica Stago, Asniéres sur Seine, France). Genesia® is a fully automated TG analyzer. In comparison to the CAT assay, ST Genesia® provides a normalization of each TG parameter based on a reference plasma for each test aiming to reduce the interlaboratory variability as well as the variability between differed measurement runs.

Secondary Outcome Measures

Name	Time	Method
PD Parameters: D-Dimer, F1.2. Timepoint: 10 min prior to dose administration and at 20 min, 1 h, 5 h, and 12 h and 24 h after. Method of measurement: Validated analytical method performed by central lab.;Measurement of plasma level of factor VII clotting activity (FVII:C). Timepoint: 10 min prior to dose administration and at 10 min, 20 min, 1 h, 3 h, 5 h, 8 h, 12 h, 24 h and 30 h after AryoSeven or NovoSeven injection. Method of measurement: Pharmacokinetic assessment of plasma level of factor VII clotting activity. (FVII:C) will be determined by commercial Staclot® VIIa–recombinant tissue factor assay (Diagnostica Stago, Asniéres sur Seine, France).