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Trial record 27 of 28 for:    Developmental Disabilities | ( Map: Minnesota, United States )

Safety of Monthly Recombinant Factor XIII Replacement Therapy in Subjects With Congenital Factor XIII Deficiency: An Extension to Trial F13CD-1725 (mentor™2)

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ClinicalTrials.gov Identifier: NCT00978380
Recruitment Status : Completed
First Posted : September 16, 2009
Results First Posted : December 13, 2016
Last Update Posted : January 24, 2018
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Conditions Congenital Bleeding Disorder
Congenital FXIII Deficiency
Intervention Drug: catridecacog
Enrollment 63
Recruitment Details The trial was conducted at 34 sites in 12 countries as follows: Austria: 1 site; Canada: 1 site; Finland: 1 site; France: 4 sites; Germany: 4 sites; Israel: 1 site; Italy: 1 site: Japan: 2 sites; Spain: 2 sites; Switzerland: 1 site; United Kingdom: 4 sites; United States: 12 sites.
Pre-assignment Details Subjects who completed F13CD-1725 (CT.gov identifier: NCT00713648) end of trial visit were eligible to enroll in this trial. Also, new subjects diagnosed with congenital FXIII A-subunit deficiency (confirmed by genotyping at screening visit or documented results from previously performed genotyping) were enrolled to expand the safety population.
Arm/Group Title Recombinant Factor XIII (rFXIII)
Hide Arm/Group Description Subjects received 35 IU/kg bodyweight of rFXIII slow intravenous (i.v.) injection every 4 weeks (28 days±2 days) for a minimum period of 52 weeks until the end of trial visit. The dose was identical to the dose administered in the F13CD- 1725 trial. A total of 60 unique subjects were enrolled and exposed in the trial, but 3 of these subjects were later withdrawn and subsequently re-enrolled with new subject IDs, giving rise to a total of N=63 subjects. The unique subjects (N=60) were presented as full analysis set (FAS) while summarising adverse events to avoid double-counting.
Period Title: Overall Study
Started 63
Completed 44
Not Completed 19
Reason Not Completed
Protocol Violation             2
Withdrawal criteria             9
Unclassified             8
Arm/Group Title Recombinant Factor XIII (rFXIII)
Hide Arm/Group Description Subjects received 35 IU/kg bodyweight of rFXIII slow intravenous (i.v.) injection every 4 weeks (28 days±2 days) for a minimum period of 52 weeks until the end of trial visit. The dose was identical to the dose administered in the F13CD- 1725 trial. A total of 60 unique subjects were enrolled and exposed in the trial, but 3 of these subjects were later withdrawn and subsequently re-enrolled with new subject IDs, giving rise to a total of N=63 subjects. The unique subjects (N=60) were presented as full analysis set (FAS) while summarising adverse events to avoid double-counting.
Overall Number of Baseline Participants 63
Hide Baseline Analysis Population Description
All subjects who received trial product were considered for baseline characteristics including 3 subjects who were re-enrolled with new subject IDs.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 63 participants
31  (16.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants
Female
23
  36.5%
Male
40
  63.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 63 participants
Hispanic or Latino
7
  11.1%
Not Hispanic or Latino
52
  82.5%
Unknown or Not Reported
4
   6.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 63 participants
American Indian or Alaska Native 1
Asian 9
Native Hawaiian or Other Pacific Islander 0
Black or African American 6
White 37
More than one race 0
Unknown or Not Reported 4
Other 6
1.Primary Outcome
Title Adverse Events (AEs)(Serious and Non-serious)
Hide Description An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Trial AEs (serious) included any event such as death, life-threatening experience, in-subject hospitalisation, significant disability/ congential anomaly experienced from the trial product.
Time Frame All AEs were collected and reported from screening (week 0) for a minimum period of 52 weeks or until the end of trial visit.
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included the 60 unique subjects exposed to trial product in this extension trial.
Arm/Group Title Recombinant Factor XIII (rFXIII)
Hide Arm/Group Description:
Subjects received 35 IU/kg bodyweight of rFXIII slow intravenous (i.v.) injection every 4 weeks (28 days±2 days) for a minimum period of 52 weeks until the end of trial visit. The dose was identical to the dose administered in the F13CD- 1725 trial. A total of 60 unique subjects were enrolled and exposed in the trial, but 3 of these subjects were later withdrawn and subsequently re-enrolled with new subject IDs, giving rise to a total of N=63 subjects. The unique subjects (N=60) were presented as full analysis set (FAS) while summarising adverse events to avoid double-counting.
Overall Number of Participants Analyzed 60
Measure Type: Number
Unit of Measure: Events
All adverse events 920
Serious adverse events 19
Non-serious adverse events 901
2.Secondary Outcome
Title Antibody and Inhibitor Development
Hide Description All subjects who received rFXIII were monitored for anti-rFXIII antibodies and inhibitor development. Samples passed through 2 tiers of ELISA testing: an initial screen with a specific cut-off point (including ~5% false positives) and a second confirmatory assay for samples yielding a result above the screening cut-off point. If samples were confirmed as antibody positive in the confirmation assay, an inhibitor assay was also carried out to detect functional inhibitors. Percentage of subjects with antibody and inhibitor development were reported.
Time Frame From week 0 to week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set included all subjects exposed to trial product in this extension trial.
Arm/Group Title Recombinant Factor XIII (rFXIII)
Hide Arm/Group Description:
Subjects received 35 IU/kg bodyweight of rFXIII slow intravenous (i.v.) injection every 4 weeks (28 days±2 days) for a minimum period of 52 weeks until the end of trial visit. The dose was identical to the dose administered in the F13CD- 1725 trial. A total of 60 unique subjects were enrolled and exposed in the trial, but 3 of these subjects were later withdrawn and subsequently re-enrolled with new subject IDs, giving rise to a total of N=63 subjects. The unique subjects (N=60) were presented as full analysis set (FAS) while summarising adverse events to avoid double-counting.
Overall Number of Participants Analyzed 63
Measure Type: Number
Unit of Measure: Percentage of subjects
0
Time Frame All adverse events (AEs) were collected and reported from screening (week 0) for a minimum period of 52 weeks or until the end of trial visit.
Adverse Event Reporting Description The FAS was used for AEs. In the early stage of the trial, a contract manufacturing facility (Avecia) produced the drug. Later, Novo Nordisk took over production of the drug. Hence, AE data are presented seperately who received both rFXIII Avecia and Novo Nordisk. Subsequently, subjects were counted under both groups.
 
Arm/Group Title rFXIII Novo Nordisk rFXIII Avecia
Hide Arm/Group Description Subjects in this arm received identical dose of 35 IU/kg bodyweight of rFXIII slow intravenous (i.v.) administered every 4 weeks (28 days±2 days) until the end of trial for a minimum period of 52 weeks. In the early stage of the trial, a contract manufacturing facility (Avecia) produced the rFXIII drug substance (rFXIII Avecia) and subsequently, Novo Nordisk took over production of the rFXIII drug substance (rFXIII Novo Nordisk). Characterisation testing between the two products confirmed that rFXIII Novo Nordisk and rFXIII Avecia had identical structures, and similar physico-chemical properties. The AE data are presented seperately for rFXIII Novo Nordisk and rFXIII Avecia. However, subjects in this arm received rFXIII Novo Nordisk drug. Subjects in this arm received identical dose of 35 IU/kg bodyweight of rFXIII slow intravenous (i.v.) administered every 4 weeks (28 days±2 days) until the end of trial for a minimum period of 52 weeks. In the early stage of the trial, a contract manufacturing facility (Avecia) produced the rFXIII drug substance (rFXIII Avecia) and subsequently, Novo Nordisk took over production of the rFXIII drug substance (rFXIII Novo Nordisk). Characterisation testing between the two products confirmed that rFXIII Novo Nordisk and rFXIII Avecia had identical structures, and similar physico-chemical properties. The AE data are presented seperately for rFXIII Novo Nordisk and rFXIII Avecia. However, subjects in this arm received rFXIII Avecia drug.
All-Cause Mortality
rFXIII Novo Nordisk rFXIII Avecia
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
rFXIII Novo Nordisk rFXIII Avecia
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/59 (20.34%)      0/26 (0.00%)    
Congenital, familial and genetic disorders     
Atrial septal defect  1  1/59 (1.69%)  1 0/26 (0.00%)  0
Patent ductus arteriosus  1  1/59 (1.69%)  1 0/26 (0.00%)  0
Gastrointestinal disorders     
Inguinal hernia  1  1/59 (1.69%)  1 0/26 (0.00%)  0
Infections and infestations     
Diverticulitis  1  1/59 (1.69%)  1 0/26 (0.00%)  0
Otitis media chronic  1  1/59 (1.69%)  1 0/26 (0.00%)  0
Injury, poisoning and procedural complications     
Chest injury  1  1/59 (1.69%)  1 0/26 (0.00%)  0
Fall  1  2/59 (3.39%)  2 0/26 (0.00%)  0
Head injury  1  2/59 (3.39%)  2 0/26 (0.00%)  0
Laceration  1  1/59 (1.69%)  1 0/26 (0.00%)  0
Multiple fractures  1  1/59 (1.69%)  1 0/26 (0.00%)  0
Road traffic accident  1  2/59 (3.39%)  2 0/26 (0.00%)  0
Spinal cord injury  1  1/59 (1.69%)  1 0/26 (0.00%)  0
Nervous system disorders     
Cerebral ischaemia  1  1/59 (1.69%)  1 0/26 (0.00%)  0
Headache  1  1/59 (1.69%)  1 0/26 (0.00%)  0
Pregnancy, puerperium and perinatal conditions     
Ectopic pregnancy  1  1/59 (1.69%)  1 0/26 (0.00%)  0
Psychiatric disorders     
Suicide attempt  1  1/59 (1.69%)  1 0/26 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
rFXIII Novo Nordisk rFXIII Avecia
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   54/59 (91.53%)      15/26 (57.69%)    
Blood and lymphatic system disorders     
Anaemia  1  4/59 (6.78%)  6 0/26 (0.00%)  0
Ear and labyrinth disorders     
Ear pain  1  4/59 (6.78%)  4 0/26 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain  1  5/59 (8.47%)  6 0/26 (0.00%)  0
Constipation  1  5/59 (8.47%)  5 0/26 (0.00%)  0
Dental caries  1  3/59 (5.08%)  4 0/26 (0.00%)  0
Diarrhoea  1  3/59 (5.08%)  3 1/26 (3.85%)  1
Dyspepsia  1  6/59 (10.17%)  14 0/26 (0.00%)  0
Nausea  1  7/59 (11.86%)  8 0/26 (0.00%)  0
Toothache  1  4/59 (6.78%)  6 0/26 (0.00%)  0
Vomiting  1  3/59 (5.08%)  4 0/26 (0.00%)  0
General disorders     
Fatigue  1  3/59 (5.08%)  3 0/26 (0.00%)  0
Pain  1  3/59 (5.08%)  4 0/26 (0.00%)  0
Pyrexia  1  6/59 (10.17%)  11 0/26 (0.00%)  0
Immune system disorders     
Seasonal allergy  1  3/59 (5.08%)  4 0/26 (0.00%)  0
Infections and infestations     
Folliculitis  1  3/59 (5.08%)  4 0/26 (0.00%)  0
Gastroenteritis  1  8/59 (13.56%)  10 0/26 (0.00%)  0
Influenza  1  7/59 (11.86%)  8 0/26 (0.00%)  0
Nasopharyngitis  1  19/59 (32.20%)  48 2/26 (7.69%)  2
Sinusitis  1  11/59 (18.64%)  17 1/26 (3.85%)  1
Tonsillitis  1  5/59 (8.47%)  8 0/26 (0.00%)  0
Upper respiratory tract infection  1  14/59 (23.73%)  25 0/26 (0.00%)  0
Viral infection  1  3/59 (5.08%)  4 0/26 (0.00%)  0
Injury, poisoning and procedural complications     
Arthropod bite  1  4/59 (6.78%)  4 0/26 (0.00%)  0
Contusion  1  11/59 (18.64%)  18 2/26 (7.69%)  2
Fall  1  8/59 (13.56%)  10 1/26 (3.85%)  1
Head injury  1  3/59 (5.08%)  4 1/26 (3.85%)  1
Incorrect dose administered  1  6/59 (10.17%)  9 1/26 (3.85%)  1
Injury  1  4/59 (6.78%)  4 0/26 (0.00%)  0
Joint injury  1  4/59 (6.78%)  6 0/26 (0.00%)  0
Laceration  1  4/59 (6.78%)  4 1/26 (3.85%)  1
Ligament sprain  1  6/59 (10.17%)  9 2/26 (7.69%)  2
Limb injury  1  5/59 (8.47%)  8 3/26 (11.54%)  3
Post-traumatic pain  1  3/59 (5.08%)  4 0/26 (0.00%)  0
Procedural pain  1  3/59 (5.08%)  3 0/26 (0.00%)  0
Road traffic accident  1  3/59 (5.08%)  3 0/26 (0.00%)  0
Skin abrasion  1  3/59 (5.08%)  4 1/26 (3.85%)  1
Thermal burn  1  6/59 (10.17%)  6 2/26 (7.69%)  2
Wound  1  2/59 (3.39%)  2 2/26 (7.69%)  2
Investigations     
White blood cells urine positive  1  3/59 (5.08%)  3 0/26 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia  1  11/59 (18.64%)  24 1/26 (3.85%)  1
Back pain  1  9/59 (15.25%)  12 2/26 (7.69%)  2
Musculoskeletal pain  1  6/59 (10.17%)  7 0/26 (0.00%)  0
Musculoskeletal stiffness  1  4/59 (6.78%)  4 0/26 (0.00%)  0
Myalgia  1  3/59 (5.08%)  5 0/26 (0.00%)  0
Neck pain  1  3/59 (5.08%)  3 1/26 (3.85%)  1
Pain in extremity  1  12/59 (20.34%)  32 1/26 (3.85%)  1
Nervous system disorders     
Headache  1  19/59 (32.20%)  72 2/26 (7.69%)  4
Renal and urinary disorders     
Haematuria  1  3/59 (5.08%)  3 1/26 (3.85%)  1
Respiratory, thoracic and mediastinal disorders     
Cough  1  12/59 (20.34%)  29 0/26 (0.00%)  0
Nasal congestion  1  7/59 (11.86%)  20 0/26 (0.00%)  0
Oropharyngeal pain  1  11/59 (18.64%)  31 0/26 (0.00%)  0
Rhinorrhoea  1  3/59 (5.08%)  4 0/26 (0.00%)  0
Skin and subcutaneous tissue disorders     
Acne  1  4/59 (6.78%)  5 0/26 (0.00%)  0
Dermatitis contact  1  3/59 (5.08%)  3 0/26 (0.00%)  0
Pruritus  1  3/59 (5.08%)  5 0/26 (0.00%)  0
Rash  1  5/59 (8.47%)  8 0/26 (0.00%)  0
Vascular disorders     
Hypertension  1  3/59 (5.08%)  4 0/26 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Limitations of the trial include small number of children and adolescents (16 subjects), and the sensitivity of the Berichrome® FXIII activity assay. However, mean FXIII activity levels were consistent with few bleeds requiring haemostatic treatment.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
At the end of the trial, one or more scientific publication will be prepared collaboratively between Investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Registry (GCR, 1452)
Organization: Novo Nordisk A/S
EMail: clinicaltrials@novonordisk.com
Layout table for additonal information
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00978380     History of Changes
Other Study ID Numbers: F13CD-3720
2008-007883-41 ( EudraCT Number )
U1111-1111-9289 ( Other Identifier: WHO )
JapicCTI-121958 ( Registry Identifier: JAPIC )
First Submitted: September 15, 2009
First Posted: September 16, 2009
Results First Submitted: October 19, 2016
Results First Posted: December 13, 2016
Last Update Posted: January 24, 2018