Congenital Bleeding Disorder, Congenital FXIII Deficiency
Conditions
Brief summary
This trial is conducted in Asia, Europe and North America. The aim of the trial is to investigate the safety of monthly replacement therapy of recombinant factor XIII in patients with congenital FXIII deficiency. The trial continues until the product is commercially available, but an interim assessment will take place when all subjects have completed 52 weeks in the trial.
Interventions
DRUGcatridecacog
Monthly administration of recombinant factor XIII as preventative treatment of bleeding episodes. Dose: 35 IU/kg body weight intravenous (into the vein)
Sponsors
Novo Nordisk A/S
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For subjects who participated in F13CD-1725: * Previous participation (means up to and inclusive Visit 16, (End of Trial)) in F13CD-1725 * For all other subjects: * Diagnosis of congenital FXIII A-subunit deficiency (confirmed by genotyping at screening visit or documented results from previously performed genotyping) * Body weight at least 20 kg
Exclusion criteria
* Known neutralizing antibodies (inhibitors) towards FXIII * Any known congenital or acquired coagulation disorder other than congenital FXIII deficiency * Platelet count (thrombocytes) of less than 50 × 109/L. For subjects who participated in F13CD-1725 platelet count from visit 15 in F13CD-1725 must be used for evaluation. * Females of childbearing potential who are pregnant, breastfeeding or are not using adequate contraceptive methods
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AEs)(Serious and Non-serious) | All AEs were collected and reported from screening (week 0) for a minimum period of 52 weeks or until the end of trial visit. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antibody and Inhibitor Development | From week 0 to week 52 | 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. |
Countries
Austria, Canada, Finland, France, Germany, Israel, Italy, Japan, Spain, Switzerland, United Kingdom, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Recombinant Factor XIII (rFXIII) 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. | 63 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 2 |
| Overall Study | Unclassified | 8 |
| Overall Study | Withdrawal criteria | 9 |
Baseline characteristics
| Characteristic | Recombinant Factor XIII (rFXIII) |
|---|---|
| Age, Continuous | 31 Years STANDARD_DEVIATION 16.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Asian | 9 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Other | 6 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 4 Participants |
| Race/Ethnicity, Customized White | 37 Participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 54 / 59 | 15 / 26 |
| serious Total, serious adverse events | 12 / 59 | 0 / 26 |
Outcome results
Primary
Adverse Events (AEs)(Serious and Non-serious)
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.
Population: The FAS included the 60 unique subjects exposed to trial product in this extension trial.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Recombinant Factor XIII (rFXIII) | Adverse Events (AEs)(Serious and Non-serious) | All adverse events | 920 Events |
| Recombinant Factor XIII (rFXIII) | Adverse Events (AEs)(Serious and Non-serious) | Serious adverse events | 19 Events |
| Recombinant Factor XIII (rFXIII) | Adverse Events (AEs)(Serious and Non-serious) | Non-serious adverse events | 901 Events |
Secondary
Antibody and Inhibitor Development
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
Population: The safety analysis set included all subjects exposed to trial product in this extension trial.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recombinant Factor XIII (rFXIII) | Antibody and Inhibitor Development | 0 Percentage of subjects |