Safety and Efficacy of Monthly Replacement Therapy With Recombinant Factor XIII (rFXIII) in Paediatric Subjects With Congenital Factor XIII A-subunit Deficiency

Study Overview
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Brief Summary
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This trial will be conducted in Asia, Europe and the United States of America (USA). The aim of this clinical trial is to investigate long-term safety of rFXIII when administered for prevention of bleeding episodes in children aged between 1 and 6 years with congenital FXIII A-subunit deficiency. This trial is an extension to trial F13CD-3760 (mentor™4, NCT01230021). If applicable the trial will be extended up to maximum 3 years dependent on when recombinant factor XIII will be commercially available in subject's respective country for use in children of 1-6 years of age.

Official Title
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A Multi-Centre, Multinational, Open-Label, Single-Arm and Multiple Dosing Trial on Safety and Efficacy of Monthly Replacement Therapy With Recombinant Factor XIII (rFXIII) in Paediatric Subjects With Congenital Factor XIII A-subunit Deficiency. Safety Extension Trial to F13CD-3760

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: Completed participation in trial F13CD-3760 (NCT01230021) Exclusion Criteria: Known or suspected hypersensitivity to trial product or related products Known history of development of inhibitors against FXIII (factor XIII) Hereditary or acquired coagulation disorder other than FXIII congenital deficiency Platelet count (thrombocytes) less than 50X10e9 / L Previous history of autoimmune disorder involving autoantibodies e.g., systemic lupus erythematosus Previous history of arterial or venous thromboembolic events e.g., cerebrovascular accident or deep vein thrombosis Any disease or condition which, judged by the trial physician, could imply a potential hazard to the subject, interfere with the trial participation or trial outcome including renal and/or liver dysfunction

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum 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: rFXIII 35 IU/kg<br> | Drug: catridecacog<br>* Intravenous injection of a single dose of recombinant factor XIII, 35 IU/kg body weight every 4th week<br>* Other names: recombinant factor XIII;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment Emergent (Serious and Non-serious) Adverse Events | An adverse event was described as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, and which does not necessarily have a causal relationship with this treatment. Treatment emergent adverse events (serious and non-serious), defined as adverse events occurring from first trial product administration to the end of the subject's participation in the trial. | Week 0 to end of trial visit (week 173) for a minimum period of 52 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Development of Anti-rFXIII Antibodies, Including Inhibitors. | All subjects who received rFXIII were monitored for the frequency of development of anti-rFXIII antibodies. Samples passed through 2 tiers of ELISA testing: an initial screen with a specific cut-off point (including  5% false positives) and a second confirmatory assay for samples yielding a result above the screening cut-off point. If samples were confirmed as antibody positive in the confirmation assay, an inhibitor assay was also carried out to detect functional inhibitors. | Week 0 to end of trial visit (week 173). | 
| Clinical Laboratory Assessments: Biochemistry: Creatinine | Clinical laboratory assessments for creatinine at week 24 to end of trial visit. | Every 6th month, from week 24 to end of trial visit (week 173). | 
| Clinical Laboratory Assessments: Biochemistry: Urea | Clinical laboratory assessments for urea at week 24 to end ot trial visit. | Every 6th month, week 24 to end of trial visit (week 173). | 
| Clinical Laboratory Assessments: Biochemistry: Alanine Aminotransferase (ALAT) | Clinical laboratory assessments for ALAT at week 24 to end of trial visit. | Every 6th month, from week 24 to end of trial visit (week 173). | 
| Clinical Laboratory Assessments: Biochemistry: Aspartate Aminotransferase (ASAT) | Clinical laboratory assessments for ASAT at week 24 to end of trial visit. | Every 6th month, from week 24 to end of trial visit (week 173). | 
| Clinical Laboratory Assessments: Haematology: Haemoglobin | Clinical values for haemoglobin collected from week 0 to end of trial visit. | Every 6th month, from week 0 to end of trial visit (week 173). | 
| Clinical Laboratory Assessments: Haematology: Leucocytes | Clinical laboratory values for leucocytes collected from week 0 to end of trial visit. | Every 6th month, from week 0 to end of trial visit (week 173). | 
| Clinical Laboratory Assessments: Haematology: Thrombocytes | Clinical laboratory values for thrombocytes collected from week 0 to end of trial visit. | Every 6th month, from week 0 to end of trial visit (week 173). | 
| Clinical Laboratory Assessments: Haematology: Erythrocytes | Clinical laboratory values for erythrocytes collected from week 0 to end of trial visit. | Every 6th month, from week 0 to end of trial visit (week 173). | 
| Clinical Laboratory Assessments: Haematology: Haematocrit | Clinical laboratory values for haematocrit collected from week 0 to end of trial visit. | Every 6th month, from week 0 to end of trial visit (week 173). | 
| Physical Examinations | Number of subjects in percentage with changes in values of physical examinations from week 0 to end of trial visit were collected. | Week 0 to end of trial visit (week 173). | 
| Vital Signs: Systolic BP (Blood Pressure) | Values collected for systolic BP from week 0 to end of trial visit. | Week 0 to end of trial visit (week 173). | 
| Vital Signs: Diastolic BP (Blood Pressure) | Values collected for diastolic BP from week 0 to end of trial visit. | Week 0 to end of trial visit (week 173). | 
| Vital Signs: Pulse | Values collected for pulse from week 0 to end of trial visit. | Week 0 to end of trial visit (week 173). | 
| Rate (Number Per Subject Year) of All Bleeding Episodes Requiring Treatment With a FXIII Containing Product Other Than Recombinant Factor XIII. | The rate (number per subject year) of all spontaneous, traumatic and intracranial bleeding episodes requiring treatment with FXIII-containing products during the rFXIII treatment period was assessed for treatment period. | Weeks 0 to end of trial visit (week 173). |