Evaluation of Recombinant Factor XIII for Prevention of Bleeding in Patients With FXIII Inherited Deficiency
Primary Purpose
Congenital Bleeding Disorder, Congenital FXIII Deficiency
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
catridecacog
Sponsored by
About this trial
This is an interventional prevention trial for Congenital Bleeding Disorder
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of congenital FXIII A-subunit deficiency (confirmed by genotyping at screening visit)
- Treatment with regular FXIII replacement therapy initiated at least 6 months prior to screening and one of the following : a documented history of at least one 1 treatment-requiring bleeding episode prior to initiation of regular replacement therapy or a documented family history of FXIII congenital deficiency (only for subjects on regular replacement therapy prior to screening)
- Documented history of at least two 2 bleeding episodes requiring treatment with FXIII containing blood products within the last 12 months prior to screening (only for subjects receiving on-demand treatment prior to screening)
Exclusion Criteria:
- Known neutralizing antibodies (inhibitors) towards FXIII
- Any known congenital or acquired coagulation disorder other than congenital FXIII deficiency
- Documented history of at least 2 treatment-requiring bleeding episodes per year during previous regular replacement therapy with FXIII containing blood products (fresh frozen plasma (FFP), plasma-derived FXIII (pd FXIII) and cryoprecipitate)
- Known or suspected allergy to trial product(s) or related products
- Planned major surgery during the trial period. Catheter, ports and dental extractions do not count as surgeries and will not exclude the subject
- Renal insufficiency defined as current dialysis therapy
- Any history of confirmed venous or arterial thrombo-embolic events
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
- 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
- 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
- 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
rFXIII
Arm Description
Outcomes
Primary Outcome Measures
Rate (Number Per Subject Year) of Bleeding Episodes Requiring Treatment With a FXIII Containing Product During the Treatment Period
It represents the incidence of bleeding episodes requiring treatment with a FXIII-containing product.
Secondary Outcome Measures
Percentage of Subjects Having a Normal Clot Solubility One Hour After rFXIII Administration and 28 Days After rFXIII Administration for All Dosing Visits
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).
Level of FXIII Activity One Hour After rFXIII Administration and 28 Days After rFXIII Administration for All Dosing Visits
Subjects entered a 52-week treatment period of monthly (28±2 days) doses of 35 IU/kg rFXIII. Blood samples for analysis of FXIII activity were drawn at each visit; at dosing visits blood was drawn 1 hour after administration and before administration(corresponding to 28 days after the previous dose). All Dosing Visits are visits where a dose is given (i.e. Visit 2-15 except Visit 3).
Number of Subjects With rFXIII Antibody Development
Subjects receiving rFXIII were monitored for the development of binding antibodies. Blood sampling was done before administration of trial product at all visits (Visits 1-16 and unscheduled visit)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00713648
Brief Title
Evaluation of Recombinant Factor XIII for Prevention of Bleeding in Patients With FXIII Inherited Deficiency
Official Title
A Multi-Centre, Open-Label, Single-Arm and Multiple Dosing Trial on Efficacy and Safety of Monthly Replacement Therapy With Recombinant Factor XIII (rFXIII) in Subjects With Congenital Factor XIII Deficiency
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
August 2008 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
April 2010 (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
The trial is conducted in Europe, North America and Asia. The aim of this trial is to evaluate catridecacog (recombinant factor XIII (rFXIII)) treatment in patients with inherited FXIII deficiency. It is expected that recombinant FXIII can be used for the prevention of bleeding episodes.
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
Prevention
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
rFXIII
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
catridecacog
Intervention Description
35 IU/kg body weight, i.v. administration, once every 4 weeks
Primary Outcome Measure Information:
Title
Rate (Number Per Subject Year) of Bleeding Episodes Requiring Treatment With a FXIII Containing Product During the Treatment Period
Description
It represents the incidence of bleeding episodes requiring treatment with a FXIII-containing product.
Time Frame
For a period of 322 days (approximately one year) comprised of a screening visit (Visit 1), treatment period (Visits 2-15), unscheduled visit and end-of-trial visit (Visit 16).
Secondary Outcome Measure Information:
Title
Percentage of Subjects Having a Normal Clot Solubility One Hour After rFXIII Administration and 28 Days After rFXIII Administration for All Dosing Visits
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
For a period of 322 days (approximately one year) comprised of a screening visit (Visit 1), treatment period (Visits 2-15), unscheduled visit and end-of-trial visit (Visit 16).
Title
Level of FXIII Activity One Hour After rFXIII Administration and 28 Days After rFXIII Administration for All Dosing Visits
Description
Subjects entered a 52-week treatment period of monthly (28±2 days) doses of 35 IU/kg rFXIII. Blood samples for analysis of FXIII activity were drawn at each visit; at dosing visits blood was drawn 1 hour after administration and before administration(corresponding to 28 days after the previous dose). All Dosing Visits are visits where a dose is given (i.e. Visit 2-15 except Visit 3).
Time Frame
For a period of 322 days (approximately one year) comprised of a screening visit (Visit 1), treatment period (Visits 2-15), unscheduled visit and end-of-trial visit (Visit 16).
Title
Number of Subjects With rFXIII Antibody Development
Description
Subjects receiving rFXIII were monitored for the development of binding antibodies. Blood sampling was done before administration of trial product at all visits (Visits 1-16 and unscheduled visit)
Time Frame
For a period of 322 days (approximately one year) comprised of a screening visit (Visit 1), treatment period (Visits 2-15), unscheduled visit and end-of-trial visit (Visit 16).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of congenital FXIII A-subunit deficiency (confirmed by genotyping at screening visit)
Treatment with regular FXIII replacement therapy initiated at least 6 months prior to screening and one of the following : a documented history of at least one 1 treatment-requiring bleeding episode prior to initiation of regular replacement therapy or a documented family history of FXIII congenital deficiency (only for subjects on regular replacement therapy prior to screening)
Documented history of at least two 2 bleeding episodes requiring treatment with FXIII containing blood products within the last 12 months prior to screening (only for subjects receiving on-demand treatment prior to screening)
Exclusion Criteria:
Known neutralizing antibodies (inhibitors) towards FXIII
Any known congenital or acquired coagulation disorder other than congenital FXIII deficiency
Documented history of at least 2 treatment-requiring bleeding episodes per year during previous regular replacement therapy with FXIII containing blood products (fresh frozen plasma (FFP), plasma-derived FXIII (pd FXIII) and cryoprecipitate)
Known or suspected allergy to trial product(s) or related products
Planned major surgery during the trial period. Catheter, ports and dental extractions do not count as surgeries and will not exclude the subject
Renal insufficiency defined as current dialysis therapy
Any history of confirmed venous or arterial thrombo-embolic events
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
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016-7710
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33607
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
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
East Lansing
State/Province
Michigan
ZIP/Postal Code
48823
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
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Novo Nordisk Investigational Site
City
Graz
ZIP/Postal Code
8036
Country
Austria
Facility Name
Novo Nordisk Investigational Site
City
Klagenfurt
ZIP/Postal Code
A-9020
Country
Austria
Facility Name
Novo Nordisk Investigational Site
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Novo Nordisk Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Novo Nordisk Investigational Site
City
Helsinki
ZIP/Postal Code
00290
Country
Finland
Facility Name
Novo Nordisk Investigational Site
City
Le Kremlin Bicetre
ZIP/Postal Code
94270
Country
France
Facility Name
Novo Nordisk Investigational Site
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Novo Nordisk Investigational Site
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
Novo Nordisk Investigational Site
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Novo Nordisk Investigational Site
City
Braunschweig
ZIP/Postal Code
38118
Country
Germany
Facility Name
Novo Nordisk Investigational Site
City
Duisburg
ZIP/Postal Code
47051
Country
Germany
Facility Name
Novo Nordisk Investigational Site
City
Petach Tikva
ZIP/Postal Code
49100
Country
Israel
Facility Name
Novo Nordisk Investigational Site
City
Tel-Hashomer
ZIP/Postal Code
52621
Country
Israel
Facility Name
Novo Nordisk Investigational Site
City
Vicenza
ZIP/Postal Code
36100
Country
Italy
Facility Name
Novo Nordisk Investigational Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novo Nordisk Investigational Site
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Novo Nordisk Investigational Site
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland
Facility Name
Novo Nordisk Investigational Site
City
Aberdeen
ZIP/Postal Code
AB25 2ZN
Country
United Kingdom
Facility Name
Novo Nordisk Investigational Site
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Facility Name
Novo Nordisk Investigational Site
City
Bradford
ZIP/Postal Code
BD9 6RJ
Country
United Kingdom
Facility Name
Novo Nordisk Investigational Site
City
Bristol
ZIP/Postal Code
BS2 8ED
Country
United Kingdom
Facility Name
Novo Nordisk Investigational Site
City
Liverpool
ZIP/Postal Code
L12 2AP
Country
United Kingdom
Facility Name
Novo Nordisk Investigational Site
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Facility Name
Novo Nordisk Investigational Site
City
Newcastle upon Tyne
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
22451421
Citation
Inbal A, Oldenburg J, Carcao M, Rosholm A, Tehranchi R, Nugent D. Recombinant factor XIII: a safe and novel treatment for congenital factor XIII deficiency. Blood. 2012 May 31;119(22):5111-7. doi: 10.1182/blood-2011-10-386045. Epub 2012 Mar 26.
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
Evaluation of Recombinant Factor XIII for Prevention of Bleeding in Patients With FXIII Inherited Deficiency
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