Safety of a Single Intravenous Dose of Recombinant Factor XIII in Children With Congenital FXIII A-subunit Deficiency

Study Overview
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Brief Summary
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This trial is conducted in Europe and United States of America (USA). The aim of this clinical trial is to investigate the pharmacokinetics (at which rate the substance is distributed and eliminated from the body) and the safety profile of catridecacog (recombinant factor XIII (rFXIII)) in children with congenital FXIII A-subunit deficiency. Young children (1 to less than 6 years old) with congenital FXIII deficiency are evaluated.

Official Title
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A Phase 3b Trial Investigating the Pharmacokinetics and Safety Profile of a Single Intravenous Dose of rFXIII in Paediatric (1 to Less Than 6 Years Old) Subjects With Congenital FXIII A-subunit 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: Signed Informed Consent by subject's parents or subject's legally acceptable representative before any trial related activities. Trial related activities are any procedures that would not have been performed during the normal management of the subject Age 1 to less than 6 years old at the time of enrolment Congenital FXIII subunit-A deficiency previously documented by genotyping or evaluated by genotyping through blood sampling at screening visit Body weight at least 10 kg Exclusion Criteria: Known antibodies to FXIII Hereditary or acquired coagulation disorder other than FXIII A-subunit congenital deficiency Platelet count (thrombocytes) of less than 50 × 10^9/L (at screening visit) 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 Known or suspected allergy to trial product or related products Any surgical procedure in the 30 days prior to enrolment and any planned surgery during the trial period Any disease or condition which, judged by the Investigator, could imply a potential hazard to the subject or 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: recombinant factor XIII<br> | Drug: catridecacog<br>* Intravenous injection of a single dose of recombinant factor XIII, 35 IU/kg bodyweight<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration vs. Time Curve (AUC) | A measure of the exposure. Blood samples for the PK assessment were drawn pre-dose and up to 30 days after dosing. The PK of FXIII in children was assessed after a single i.v. dose of rFXIII 35 IU/kg. | At pre-dose, 30 minutes, 24 hours, 7, 14, 21 and 30 days after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration vs. Time Curve (AUC0-∞) | A measure of exposure. | From day 0 to day 30 | 
| Maximum Plasma Concentration (Cmax) for FXIII | Maximum plasma concentration of the drug reached. | At pre-dose, 30 minutes, 24 hours, 7, 14, 21 and 30 days after dosing | 
| Terminal Half-life (t½) | Time point when half of the maximum plasma concentration is reached. | From day 0 to day 30 | 
| Mean Residence Time (MRT) | The mean residence time (MRT) of a drug in the body and related functions are derived for drugs which are intravenously administered. | From day 0 to day 30 | 
| Total Plasma Clearance (CL) | The total plasma clearance is a measure of the elimination of a drug from the body. Drugs are excreted primarily by the kidneys into the urine. Clearance is calculated as 'CL=Dose / AUC0-30 days'). | From day 0 to day 30 | 
| Volume of Distribution at Steady State (Vss) | Volume of distribution at steady state (Vss) is the theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it is in blood plasma at steady state. Steady state is achieved when all variables are constant in spite of ongoing processes. | At steady state | 
| Percentage of Subjects With One or More Adverse Events (AEs) Recorded |  | From day 0 to day 30 | 
| Percentage of Subjects With One or More Serious Adverse Events (SAEs) |  | From day 0 to day 30 | 
| Percentage of Subjects With Development of Anti-rFXIII Antibodies, Including Inhibitors (Neutralising Antibodies Against Factor XIII) |  | At screening and day 30 | 
| Coagulation Related Parameters - Fibrinogen |  | Day 0 and at day 30 | 
| Coagulation Related Parameters - Activated Partial Thromboplastin Time (aPTT, Seconds) |  | Day 0 and day 30 | 
| Coagulation Related Parameters - Prothrombin Time (PT) (Seconds) |  | Day 0 and day 30 | 
| Clot Solubility Test (Evaluated as Normal/Abnormal) | 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). | Day 0 and day 30 | 
| Vital Signs - Pulse |  | Day 0 and day 30 | 
| Vital Signs - Blood Pressure (Systolic and Diastolic) |  | Day 0 and day 30 | 
| Physical Examination (Evaluated as Normal/Abnormal) |  | From day 0 to day 30 |