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

Congenital Bleeding Disorder Clinical Trial

— mentor™4  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01230021
• Other study ID #: F13CD-3760
• Secondary ID: U1111-1116-25332
• Status: Completed
• Phase: Phase 3
• First received: October 27, 2010
• Last updated: September 3, 2014
• Start date: November 2010
• Est. completion date: January 2012

Study information

• Verified date: September 2014
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 6 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Congenital Bleeding Disorder
• Congenital FXIII Deficiency
• Hemostatic Disorders

Intervention

Drug:
• catridecacog
Intravenous injection of a single dose of recombinant factor XIII, 35 IU/kg bodyweight

Locations

Country	Name	City	State
United States	Novo Nordisk Clinical Trial Call Center	Columbus	Ohio
United States	Novo Nordisk Clinical Trial Call Center	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Israel,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Area Under the Concentration vs. Time Curve (AUC0-8)	A measure of exposure.	From day 0 to day 30	No
Secondary	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	No
Secondary	Terminal Half-life (t½)	Time point when half of the maximum plasma concentration is reached.	From day 0 to day 30	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Percentage of Subjects With One or More Adverse Events (AEs) Recorded		From day 0 to day 30	No
Secondary	Percentage of Subjects With One or More Serious Adverse Events (SAEs)		From day 0 to day 30	No
Secondary	Percentage of Subjects With Development of Anti-rFXIII Antibodies, Including Inhibitors (Neutralising Antibodies Against Factor XIII)		At screening and day 30	No
Secondary	Coagulation Related Parameters - Fibrinogen		Day 0 and at day 30	No
Secondary	Coagulation Related Parameters - Activated Partial Thromboplastin Time (aPTT, Seconds)		Day 0 and day 30	No
Secondary	Coagulation Related Parameters - Prothrombin Time (PT) (Seconds)		Day 0 and day 30	No
Secondary	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	No
Secondary	Vital Signs - Pulse		Day 0 and day 30	No
Secondary	Vital Signs - Blood Pressure (Systolic and Diastolic)		Day 0 and day 30	No
Secondary	Physical Examination (Evaluated as Normal/Abnormal)		From day 0 to day 30	No

External Links

•   Clinical Trials at Novo Nordisk