Human Fibrinogen - Pharmacokinetics

Study Overview
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Brief Summary
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This study evaluated the single-dose pharmacokinetics of human fibrinogen concentrate and clot strength (maximum clot firmness [MCF]) in subjects with congenital fibrinogen deficiency. MCF was measured to demonstrate the functional activity of replacement fibrinogen when a fixed dose of human fibrinogen concentrate was administered.

Official Title
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Pharmacokinetics of Haemocomplettan® P in Subjects With Congenital Fibrinogen Deficiency

Conditions
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Fibrinogen Deficiency

Intervention / Treatment
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* Biological: Human Fibrinogen Concentrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 6 years Documented congenital fibrinogen deficiency: fibrinogen deficiency manifested as afibrinogenemia with plasma fibrinogen activity and antigen at screening undetectable (i.e. < 20 mg/dL) Informed consent signed by subject or legal guardian Exclusion Criteria: Presence or history of hypersensitivity to Human Fibrinogen Concentrate or human plasma proteins, Presence or history of deep vein thrombosis, pulmonary embolism, or arterial thrombosis Acute bleeding History of esophageal varicose bleeding End stage liver disease (i.e. Child-Pugh score B or C) Planned major surgery with a need for blood transfusion during the PK blood sampling period Polytrauma within 1 year prior to enrollment

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human Fibrinogen Concentrate<br> | Biological: Human Fibrinogen Concentrate<br>* Single intravenous infusion of 70 mg/kg body weight<br>* Other names: RiaSTAP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Clot Firmness (MCF) | MCF is a functional parameter that depends on the activation of coagulation, the fibrinogen content of the sample (in plasma), and the polymerization and crosslinking of the fibrin network. MCF was determined by rotational thromboelastometry (ROTEM) testing. | Pre-infusion and 1 hour post-infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Terminal Elimination Half-life (t1/2) | t1/2 for fibrinogen activity was determined from samples taken at 12 timepoints during the specified time frame. | 0.5 hours to 13 days post-infusion | 
| Maximum Concentration (Cmax) | Cmax for fibrinogen activity was determined from samples taken at 12 timepoints during the specified time frame. | Pre-infusion to 13 days post-infusion | 
| Area Under the Concentration-time Curve (AUC) Standardized for 70 mg/kg Body Weight Dose | AUC for fibrinogen activity was determined from samples taken at 12 timepoints during the specified time frame. | Pre-infusion to 13 days post-infusion | 
| Clearance (Cl) | Cl for fibrinogen activity was determined from samples taken at 12 timepoints during the specified time frame. | Pre-infusion to 13 days post-infusion | 
| Mean Residence Time (MRT) | MRT for fibrinogen activity was determined from samples taken at 12 timepoints during the specified time frame. | Pre-infusion to 13 days post-infusion | 
| Volume of Distribution at Steady State (Vss) | Vss for fibrinogen activity was determined from samples taken at 11 timepoints during the specified time frame. | Pre-infusion to 13 days post-infusion | 
| Incremental In Vivo Recovery (IVR) | Maximum fibrinogen activity increase in plasma per mg/kg dosed | Pre-infusion to 4 hours post-infusion | 
| Classical In Vivo Recovery (IVR) | Maximum fibrinogen activity increase in plasma times plasma volume per mg/kg dose | Pre-infusion to 4 hours post-infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Congenital fibrinogen deficiency, Fibrinogen concentrate, Pharmacokinetics, Thrombelastography