Safety of a Single Intravenous Dose of Recombinant Factor XIII in Children With Congenital FXIII A-subunit Deficiency (mentor™4)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT01230021
First received: October 27, 2010
Last updated: June 11, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Congenital Bleeding Disorder
Congenital FXIII Deficiency
Drug: catridecacog
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Novo Nordisk A/S:

Primary Outcome Measures:
  • Area Under the Concentration vs. Time Curve (AUC) [ Time Frame: At pre-dose, 30 minutes, 24 hours, 7, 14, 21 and 30 days after dosing ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Area Under the Concentration vs. Time Curve (AUC0-∞) [ Time Frame: From day 0 to day 30 ] [ Designated as safety issue: No ]
    A measure of exposure.

  • Maximum Plasma Concentration (Cmax) for FXIII [ Time Frame: At pre-dose, 30 minutes, 24 hours, 7, 14, 21 and 30 days after dosing ] [ Designated as safety issue: No ]
    Maximum plasma concentration of the drug reached.

  • Terminal Half-life (t½) [ Time Frame: From day 0 to day 30 ] [ Designated as safety issue: No ]
    Time point when half of the maximum plasma concentration is reached.

  • Mean Residence Time (MRT) [ Time Frame: From day 0 to day 30 ] [ Designated as safety issue: No ]
    The mean residence time (MRT) of a drug in the body and related functions are derived for drugs which are intravenously administered.

  • Total Plasma Clearance (CL) [ Time Frame: From day 0 to day 30 ] [ Designated as safety issue: No ]
    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').

  • Volume of Distribution at Steady State (Vss) [ Time Frame: At steady state ] [ Designated as safety issue: No ]
    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.

  • Percentage of Subjects With One or More Adverse Events (AEs) Recorded [ Time Frame: From day 0 to day 30 ] [ Designated as safety issue: No ]
  • Percentage of Subjects With One or More Serious Adverse Events (SAEs) [ Time Frame: From day 0 to day 30 ] [ Designated as safety issue: No ]
  • Percentage of Subjects With Development of Anti-rFXIII Antibodies, Including Inhibitors (Neutralising Antibodies Against Factor XIII) [ Time Frame: At screening and day 30 ] [ Designated as safety issue: No ]
  • Coagulation Related Parameters - Fibrinogen [ Time Frame: Day 0 and at day 30 ] [ Designated as safety issue: No ]
  • Coagulation Related Parameters - Activated Partial Thromboplastin Time (aPTT, Seconds) [ Time Frame: Day 0 and day 30 ] [ Designated as safety issue: No ]
  • Coagulation Related Parameters - Prothrombin Time (PT) (Seconds) [ Time Frame: Day 0 and day 30 ] [ Designated as safety issue: No ]
  • Clot Solubility Test (Evaluated as Normal/Abnormal) [ Time Frame: Day 0 and day 30 ] [ Designated as safety issue: No ]
    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).

  • Vital Signs - Pulse [ Time Frame: Day 0 and day 30 ] [ Designated as safety issue: No ]
  • Vital Signs - Blood Pressure (Systolic and Diastolic) [ Time Frame: Day 0 and day 30 ] [ Designated as safety issue: No ]
  • Physical Examination (Evaluated as Normal/Abnormal) [ Time Frame: From day 0 to day 30 ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: November 2010
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: recombinant factor XIII Drug: catridecacog
Intravenous injection of a single dose of recombinant factor XIII, 35 IU/kg bodyweight

  Eligibility

Ages Eligible for Study:   1 Year to 6 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01230021

Locations
United States, Minnesota
Novo Nordisk Clinical Trial Call Center
Minneapolis, Minnesota, United States, 55404
United States, Ohio
Novo Nordisk Clinical Trial Call Center
Columbus, Ohio, United States, 43205
Israel
Petach Tikva, Israel, 49100
United Kingdom
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Global Clinical Registry (GCR, 1452) Novo Nordisk A/S
  More Information

Additional Information:
No publications provided

Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01230021     History of Changes
Other Study ID Numbers: F13CD-3760, U1111-1116-2533, 2009-016869-28
Study First Received: October 27, 2010
Results First Received: January 22, 2014
Last Updated: June 11, 2014
Health Authority: Israel: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Blood Coagulation Disorders
Hemostatic Disorders
Hemorrhagic Disorders
Hemorrhage
Hematologic Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 29, 2014