Evaluation of Recombinant Factor XIII for Prevention of Bleeding in Patients With FXIII Inherited Deficiency

Study Overview
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Brief Summary
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The trial is conducted in Europe, North America and Asia. The aim of this trial is to evaluate catridecacog (recombinant factor XIII (rFXIII)) treatment in patients with inherited FXIII deficiency. It is expected that recombinant FXIII can be used for the prevention of bleeding episodes.

Official Title
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A Multi-Centre, Open-Label, Single-Arm and Multiple Dosing Trial on Efficacy and Safety of Monthly Replacement Therapy With Recombinant Factor XIII (rFXIII) in Subjects With Congenital Factor XIII Deficiency

Conditions
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Congenital Bleeding Disorder, Congenital FXIII Deficiency

Intervention / Treatment
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* Drug: catridecacog


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of congenital FXIII A-subunit deficiency (confirmed by genotyping at screening visit) Treatment with regular FXIII replacement therapy initiated at least 6 months prior to screening and one of the following : a documented history of at least one 1 treatment-requiring bleeding episode prior to initiation of regular replacement therapy or a documented family history of FXIII congenital deficiency (only for subjects on regular replacement therapy prior to screening) Documented history of at least two 2 bleeding episodes requiring treatment with FXIII containing blood products within the last 12 months prior to screening (only for subjects receiving on-demand treatment prior to screening) Exclusion Criteria: Known neutralizing antibodies (inhibitors) towards FXIII Any known congenital or acquired coagulation disorder other than congenital FXIII deficiency Documented history of at least 2 treatment-requiring bleeding episodes per year during previous regular replacement therapy with FXIII containing blood products (fresh frozen plasma (FFP), plasma-derived FXIII (pd FXIII) and cryoprecipitate) Known or suspected allergy to trial product(s) or related products Planned major surgery during the trial period. Catheter, ports and dental extractions do not count as surgeries and will not exclude the subject Renal insufficiency defined as current dialysis therapy Any history of confirmed venous or arterial thrombo-embolic events

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: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rFXIII<br> | Drug: catridecacog<br>* 35 IU/kg body weight, i.v. administration, once every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate (Number Per Subject Year) of Bleeding Episodes Requiring Treatment With a FXIII Containing Product During the Treatment Period | It represents the incidence of bleeding episodes requiring treatment with a FXIII-containing product. | For a period of 322 days (approximately one year) comprised of a screening visit (Visit 1), treatment period (Visits 2-15), unscheduled visit and end-of-trial visit (Visit 16). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Having a Normal Clot Solubility One Hour After rFXIII Administration and 28 Days After rFXIII Administration for All Dosing Visits | Blood samples for clot solubility drawn at each visit (1 hour before and after dose administration). A clot solubility assay was used to screen for FXIII deficiency. The assay is based on the ability of urea to dissolve fibrin clots that have not undergone FXIII-induced stabilization. Normal blood clots generally remain stable for 24 hours or more, while clots in which fibrin molecules have not been cross-linked are soluble within minutes. The outcome of the test is normal (FXIII present; a clot is observed in the test tube) or abnormal (FXIII absent or very low level; no clot in test tube). | For a period of 322 days (approximately one year) comprised of a screening visit (Visit 1), treatment period (Visits 2-15), unscheduled visit and end-of-trial visit (Visit 16). | 
| Level of FXIII Activity One Hour After rFXIII Administration and 28 Days After rFXIII Administration for All Dosing Visits | Subjects entered a 52-week treatment period of monthly (28±2 days) doses of 35 IU/kg rFXIII. Blood samples for analysis of FXIII activity were drawn at each visit; at dosing visits blood was drawn 1 hour after administration and before administration(corresponding to 28 days after the previous dose). All Dosing Visits are visits where a dose is given (i.e. Visit 2-15 except Visit 3). | For a period of 322 days (approximately one year) comprised of a screening visit (Visit 1), treatment period (Visits 2-15), unscheduled visit and end-of-trial visit (Visit 16). | 
| Number of Subjects With rFXIII Antibody Development | Subjects receiving rFXIII were monitored for the development of binding antibodies. Blood sampling was done before administration of trial product at all visits (Visits 1-16 and unscheduled visit) | For a period of 322 days (approximately one year) comprised of a screening visit (Visit 1), treatment period (Visits 2-15), unscheduled visit and end-of-trial visit (Visit 16). |