A Study of Factor XIII Concentrate in Subjects With Congenital Factor XIII Deficiency

Study Overview
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Brief Summary
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Congenital deficiency of factor XIII (FXIII) is an extremely rare inherited disorder associated with potentially life-threatening bleeding. Factor XIII Concentrate is given to patients whose blood is lacking factor XIII. Factor XIII Concentrate works by assisting blood in the usual clotting process, thereby preventing bleeding. In this study, patients will be treated with FXIII Concentrate (Human) and followed closely to determine that they receive the dose that will best minimize the chance of bruising and bleeding.

Official Title
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A Prospective, Multicenter, Open-label, Phase 3b Study of Human Plasma-Derived Factor XIII Concentrate in Subjects With Congenital Factor XIII Deficiency

Conditions
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Factor XIII Deficiency

Intervention / Treatment
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* Biological: FXIII Concentrate (Human)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent/assent for study participation obtained before undergoing any study-specific procedures Documented congenital FXIII deficiency which requires prophylactic treatment with a FXIII containing product. Males and females of any age with congenital FXIII deficiency Received full hepatitis B vaccination and/or is hepatitis B surface antibody positive Exclusion Criteria: Diagnosis of acquired FXIII deficiency Administration of a FXIII-containing product, including blood transfusions or other blood products within 4 weeks prior to the planned Day 0 Any known congenital or acquired coagulation disorder other than congenital FXIII deficiency Known or suspected to have antibodies towards FXIII Use of any other investigational medicinal product within 4 weeks prior to the Baseline Visit (Day 0) Known Positivity for human immunodeficiency virus (HIV) or a positive result for HIV at the Screening Visit of this study or the FXIII study 2002 (NCT00883090). Serum aspartate transaminase (AST) or serum alanine transaminase (ALT) concentration >2.5 times the upper limit of normal at the Screening Visit of this study or at the Day 56 Visit of Factor XIII Study BI71023_2002 (NCT00883090) Fibrinogen level less than 85% of the lower limit of normal at the Screening Visit of this study or the Factor XIII Study BI71023_2002 (NCT00883090) Active bleeding ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 and/or ≥ moderate between the Screening and Baseline Visits Pregnant or breast-feeding Intention to become pregnant during the course of the study Female subjects of childbearing potential not using, or not willing to use, a medically reliable method of contraception for the entire duration of the study Suspected inability (e.g., language problems) or unwillingness to comply with study procedures or history of noncompliance
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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FXIII<br>All subjects who received a dose of Factor XIII (FXIII) Concentrate (Human). | Biological: FXIII Concentrate (Human)<br>* Doses will be guided by the individual subject's most recent FXIII activity levels, with the objective of dosing every 28 days to maintain a trough FXIII activity level of approximately 5 to 20%. Subjects enrolled in this study who did not complete the pharmacokinetic study (Factor XIII Study BI71023_2002 [NCT00883090]) will initially receive FXIII Concentrate (Human) at a dose of 40 U/kg by intravenous (IV) infusion.<br>* Other names: Fibrogammin-P;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Incidence of Spontaneous Bleeding Events Requiring Treatment (Treatment is Defined as Administration of a FXIII-Containing Product to Treat the Bleeding Event) | The number of subjects requiring treatment with a Factor XIII-containing product to treat a spontaneous bleeding event. | Up to week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association of the Incidence of Spontaneous Bleeding Events Requiring Treatment and FXIII Activity Trough Levels | P-value determined from Generalized Estimating Equation (GEE) model parameter estimates with bleeding as the response variable and FXIII activity trough level as the explanatory variable. | 12 months | 
| Adverse Events | Number of subjects with any treatment-emergent adverse event (AE), treatment-related AE or serious AE (SAE). Treatment related AEs are defined as AEs whose relationship to study treatment is related, or possibly related, and AEs with missing relationship. | 12 months | 
| Peak FXIII Concentration at Steady State |  | At 12, 24, 36 and 48 weeks: at 30 and 60 minutes after the end of the infusion. | 
| Trough FXIII Concentration at Steady State |  | At 12, 24, 36 and 48 weeks: immediately before infusion. | 
| Time to Peak Concentration |  | At 12, 24, 36 and 48 weeks: immediately before infusion, then at 30 and 60 minutes after the end of the infusion. | 
| Incremental Recovery | Incremental recovery (U/mL/U/kg) is defined as maximum (peak) FXIII activity (U/mL) obtained after infusion, per dose of (U/kg) infusion. | At 12, 24, 36 and 48 weeks: immediately before infusion, then at 30 and 60 minutes after the end of the infusion. | 
| Achievement of Trough Factor XIII Levels of 5% or Higher. | Number of subjects with Factor XIII level ≥ 5% before infusion at Week 12, Week 24, Week 36 and Week 48. | At 12, 24, 36 and 48 weeks: immediately before infusion. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hereditary Factor XIII deficiency, Factor XIII