search
Back to results

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

Primary Purpose

Congenital Bleeding Disorder, Congenital FXIII Deficiency

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
catridecacog
Sponsored by
Novo Nordisk A/S
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Congenital Bleeding Disorder

Eligibility Criteria

1 Year - 6 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site
  • Novo Nordisk Investigational Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

recombinant factor XIII

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Area Under the Concentration vs. Time Curve (AUC0-∞)
A measure of exposure.
Maximum Plasma Concentration (Cmax) for FXIII
Maximum plasma concentration of the drug reached.
Terminal Half-life (t½)
Time point when half of the maximum plasma concentration is reached.
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.
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').
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.
Percentage of Subjects With One or More Adverse Events (AEs) Recorded
Percentage of Subjects With One or More Serious Adverse Events (SAEs)
Percentage of Subjects With Development of Anti-rFXIII Antibodies, Including Inhibitors (Neutralising Antibodies Against Factor XIII)
Coagulation Related Parameters - Fibrinogen
Coagulation Related Parameters - Activated Partial Thromboplastin Time (aPTT, Seconds)
Coagulation Related Parameters - Prothrombin Time (PT) (Seconds)
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).
Vital Signs - Pulse
Vital Signs - Blood Pressure (Systolic and Diastolic)
Physical Examination (Evaluated as Normal/Abnormal)

Full Information

First Posted
October 27, 2010
Last Updated
January 10, 2017
Sponsor
Novo Nordisk A/S
search

1. Study Identification

Unique Protocol Identification Number
NCT01230021
Brief Title
Safety of a Single Intravenous Dose of Recombinant Factor XIII in Children With Congenital FXIII A-subunit Deficiency
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
November 2010 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novo Nordisk A/S

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Bleeding Disorder, Congenital FXIII Deficiency

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
recombinant factor XIII
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
catridecacog
Intervention Description
Intravenous injection of a single dose of recombinant factor XIII, 35 IU/kg bodyweight
Primary Outcome Measure Information:
Title
Area Under the Concentration vs. Time Curve (AUC)
Description
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.
Time Frame
At pre-dose, 30 minutes, 24 hours, 7, 14, 21 and 30 days after dosing
Secondary Outcome Measure Information:
Title
Area Under the Concentration vs. Time Curve (AUC0-∞)
Description
A measure of exposure.
Time Frame
From day 0 to day 30
Title
Maximum Plasma Concentration (Cmax) for FXIII
Description
Maximum plasma concentration of the drug reached.
Time Frame
At pre-dose, 30 minutes, 24 hours, 7, 14, 21 and 30 days after dosing
Title
Terminal Half-life (t½)
Description
Time point when half of the maximum plasma concentration is reached.
Time Frame
From day 0 to day 30
Title
Mean Residence Time (MRT)
Description
The mean residence time (MRT) of a drug in the body and related functions are derived for drugs which are intravenously administered.
Time Frame
From day 0 to day 30
Title
Total Plasma Clearance (CL)
Description
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').
Time Frame
From day 0 to day 30
Title
Volume of Distribution at Steady State (Vss)
Description
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.
Time Frame
At steady state
Title
Percentage of Subjects With One or More Adverse Events (AEs) Recorded
Time Frame
From day 0 to day 30
Title
Percentage of Subjects With One or More Serious Adverse Events (SAEs)
Time Frame
From day 0 to day 30
Title
Percentage of Subjects With Development of Anti-rFXIII Antibodies, Including Inhibitors (Neutralising Antibodies Against Factor XIII)
Time Frame
At screening and day 30
Title
Coagulation Related Parameters - Fibrinogen
Time Frame
Day 0 and at day 30
Title
Coagulation Related Parameters - Activated Partial Thromboplastin Time (aPTT, Seconds)
Time Frame
Day 0 and day 30
Title
Coagulation Related Parameters - Prothrombin Time (PT) (Seconds)
Time Frame
Day 0 and day 30
Title
Clot Solubility Test (Evaluated as Normal/Abnormal)
Description
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).
Time Frame
Day 0 and day 30
Title
Vital Signs - Pulse
Time Frame
Day 0 and day 30
Title
Vital Signs - Blood Pressure (Systolic and Diastolic)
Time Frame
Day 0 and day 30
Title
Physical Examination (Evaluated as Normal/Abnormal)
Time Frame
From day 0 to day 30

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Registry (GCR, 1452)
Organizational Affiliation
Novo Nordisk A/S
Official's Role
Study Director
Facility Information:
Facility Name
Novo Nordisk Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Petach Tikva
ZIP/Postal Code
49100
Country
Israel
Facility Name
Novo Nordisk Investigational Site
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Facility Name
Novo Nordisk Investigational Site
City
Leicester
ZIP/Postal Code
LE1 5WW
Country
United Kingdom
Facility Name
Novo Nordisk Investigational Site
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Facility Name
Novo Nordisk Investigational Site
City
Newcastle upon Tyne
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
Facility Name
Novo Nordisk Investigational Site
City
Reading
ZIP/Postal Code
RG1 5AN
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
23834599
Citation
Williams M, Will A, Stenmo C, Rosholm A, Tehranchi R. Pharmacokinetics of recombinant factor XIII in young children with congenital FXIII deficiency and comparison with older patients. Haemophilia. 2014 Jan;20(1):99-105. doi: 10.1111/hae.12224. Epub 2013 Jul 9.
Results Reference
result
PubMed Identifier
25643920
Citation
Brand-Staufer B, Carcao M, Kerlin BA, Will A, Williams M, Tornoe CW, Sandberg Lundblad M, Nugent D. Pharmacokinetic characterization of recombinant factor XIII (FXIII)-A2 across age groups in patients with FXIII A-subunit congenital deficiency. Haemophilia. 2015 May;21(3):380-385. doi: 10.1111/hae.12616. Epub 2015 Jan 21.
Results Reference
result
Links:
URL
http://novonordisk-trials.com
Description
Clinical Trials at Novo Nordisk

Learn more about this trial

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

We'll reach out to this number within 24 hrs