Factor XIII Deficiency
Conditions
Keywords
Hereditary Factor XIII deficiency, Factor XIII
Brief summary
Congenital deficiency of factor XIII (FXIII) is an extremely rare inherited disorder associated with potentially life-threatening bleeding. Factor XIII Concentrate is given to patients whose blood is lacking factor XIII. Factor XIII Concentrate works by assisting blood in the usual clotting process, thereby preventing bleeding. In this study, patients will be treated with FXIII Concentrate (Human) and followed closely to determine that they receive the dose that will best minimize the chance of bruising and bleeding.
Interventions
BIOLOGICALFXIII Concentrate (Human)
Doses will be guided by the individual subject's most recent FXIII activity levels, with the objective of dosing every 28 days to maintain a trough FXIII activity level of approximately 5 to 20%. Subjects enrolled in this study who did not complete the pharmacokinetic study (Factor XIII Study BI71023\_2002 \[NCT00883090\]) will initially receive FXIII Concentrate (Human) at a dose of 40 U/kg by intravenous (IV) infusion.
Sponsors
CSL Behring
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Written informed consent/assent for study participation obtained before undergoing any study-specific procedures * Documented congenital FXIII deficiency which requires prophylactic treatment with a FXIII containing product. * Males and females of any age with congenital FXIII deficiency * Received full hepatitis B vaccination and/or is hepatitis B surface antibody positive
Exclusion criteria
* Diagnosis of acquired FXIII deficiency * Administration of a FXIII-containing product, including blood transfusions or other blood products within 4 weeks prior to the planned Day 0 * Any known congenital or acquired coagulation disorder other than congenital FXIII deficiency * Known or suspected to have antibodies towards FXIII * Use of any other investigational medicinal product within 4 weeks prior to the Baseline Visit (Day 0) * Known Positivity for human immunodeficiency virus (HIV) or a positive result for HIV at the Screening Visit of this study or the FXIII study 2002 (NCT00883090). * Serum aspartate transaminase (AST) or serum alanine transaminase (ALT) concentration \>2.5 times the upper limit of normal at the Screening Visit of this study or at the Day 56 Visit of Factor XIII Study BI71023\_2002 (NCT00883090) * Fibrinogen level less than 85% of the lower limit of normal at the Screening Visit of this study or the Factor XIII Study BI71023\_2002 (NCT00883090) * Active bleeding ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 and/or ≥ moderate between the Screening and Baseline Visits * Pregnant or breast-feeding * Intention to become pregnant during the course of the study * Female subjects of childbearing potential not using, or not willing to use, a medically reliable method of contraception for the entire duration of the study * Suspected inability (e.g., language problems) or unwillingness to comply with study procedures or history of noncompliance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence of Spontaneous Bleeding Events Requiring Treatment (Treatment is Defined as Administration of a FXIII-Containing Product to Treat the Bleeding Event) | Up to week 52 | The number of subjects requiring treatment with a Factor XIII-containing product to treat a spontaneous bleeding event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 12 months | Number of subjects with any treatment-emergent adverse event (AE), treatment-related AE or serious AE (SAE). Treatment related AEs are defined as AEs whose relationship to study treatment is related, or possibly related, and AEs with missing relationship. |
| Peak FXIII Concentration at Steady State | At 12, 24, 36 and 48 weeks: at 30 and 60 minutes after the end of the infusion. | — |
| Trough FXIII Concentration at Steady State | At 12, 24, 36 and 48 weeks: immediately before infusion. | — |
| Association of the Incidence of Spontaneous Bleeding Events Requiring Treatment and FXIII Activity Trough Levels | 12 months | P-value determined from Generalized Estimating Equation (GEE) model parameter estimates with bleeding as the response variable and FXIII activity trough level as the explanatory variable. |
| Incremental Recovery | At 12, 24, 36 and 48 weeks: immediately before infusion, then at 30 and 60 minutes after the end of the infusion. | Incremental recovery (U/mL/U/kg) is defined as maximum (peak) FXIII activity (U/mL) obtained after infusion, per dose of (U/kg) infusion. |
| Achievement of Trough Factor XIII Levels of 5% or Higher. | At 12, 24, 36 and 48 weeks: immediately before infusion. | Number of subjects with Factor XIII level ≥ 5% before infusion at Week 12, Week 24, Week 36 and Week 48. |
| Time to Peak Concentration | At 12, 24, 36 and 48 weeks: immediately before infusion, then at 30 and 60 minutes after the end of the infusion. | — |
Countries
Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FXIII All subjects who received a dose of Factor XIII (FXIII) Concentrate (Human). | 41 |
| Total | 41 |
Baseline characteristics
| Characteristic | FXIII |
|---|---|
| Age Continuous | 20.1 years STANDARD_DEVIATION 11.2 |
| Age, Customized 16 to < 65 years | 23 participants |
| Age, Customized < 16 years | 18 participants |
| Age, Customized ≥ 65 years | 0 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 27 / 41 |
| serious Total, serious adverse events | 4 / 41 |
Outcome results
Primary
The Incidence of Spontaneous Bleeding Events Requiring Treatment (Treatment is Defined as Administration of a FXIII-Containing Product to Treat the Bleeding Event)
The number of subjects requiring treatment with a Factor XIII-containing product to treat a spontaneous bleeding event.
Time frame: Up to week 52
Population: The Efficacy Population comprised all subjects who received a dose of FXIII Concentrate (Human) during the study and included those who were assessed for efficacy at Baseline and had at least 1 follow-up FXIII activity trough level.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FXIII | The Incidence of Spontaneous Bleeding Events Requiring Treatment (Treatment is Defined as Administration of a FXIII-Containing Product to Treat the Bleeding Event) | 0 participants |
Secondary
Achievement of Trough Factor XIII Levels of 5% or Higher.
Number of subjects with Factor XIII level ≥ 5% before infusion at Week 12, Week 24, Week 36 and Week 48.
Time frame: At 12, 24, 36 and 48 weeks: immediately before infusion.
Population: The Efficacy Population comprised all subjects who received a dose of FXIII Concentrate (Human) during the study and included those who were assessed for efficacy at Baseline and had at least 1 follow-up FXIII activity trough level.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FXIII | Achievement of Trough Factor XIII Levels of 5% or Higher. | Week 12 (n = 40) | 40 participants |
| FXIII | Achievement of Trough Factor XIII Levels of 5% or Higher. | Week 24 (n = 41) | 41 participants |
| FXIII | Achievement of Trough Factor XIII Levels of 5% or Higher. | Week 36 (n = 41) | 41 participants |
| FXIII | Achievement of Trough Factor XIII Levels of 5% or Higher. | Week 48 (n = 41) | 40 participants |
Secondary
Adverse Events
Number of subjects with any treatment-emergent adverse event (AE), treatment-related AE or serious AE (SAE). Treatment related AEs are defined as AEs whose relationship to study treatment is related, or possibly related, and AEs with missing relationship.
Time frame: 12 months
Population: The Safety Population comprised all subjects who received a dose of FXIII Concentrate (Human) during the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FXIII | Adverse Events | Any treatment-emergent AEs | 33 participants |
| FXIII | Adverse Events | Any treatment-emergent and treatment-related AE | 3 participants |
| FXIII | Adverse Events | Any treatment-emergent SAE | 4 participants |
Secondary
Association of the Incidence of Spontaneous Bleeding Events Requiring Treatment and FXIII Activity Trough Levels
P-value determined from Generalized Estimating Equation (GEE) model parameter estimates with bleeding as the response variable and FXIII activity trough level as the explanatory variable.
Time frame: 12 months
Population: The analysis population comprised those subjects with spontaneous bleeding events requiring treatment with a FXIII-containing product. Note: no subjects had spontaneous bleeding events requiring treatment with a FXIII-containing product, so no subjects were analyzed.
Secondary
Incremental Recovery
Incremental recovery (U/mL/U/kg) is defined as maximum (peak) FXIII activity (U/mL) obtained after infusion, per dose of (U/kg) infusion.
Time frame: At 12, 24, 36 and 48 weeks: immediately before infusion, then at 30 and 60 minutes after the end of the infusion.
Population: The Pharmacokinetic (PK) Population comprised all subjects who received a dose of FXIII Concentrate (Human) during the study and included those who completed the study (defined as having sufficient bioanalytical assessments to calculate reliable estimates of the PK parameters).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FXIII | Incremental Recovery | Week 12 (n = 39) | 0.021 Units/mL/Units/kg | Standard Deviation 0.0059 |
| FXIII | Incremental Recovery | Week 24 (n = 38) | 0.023 Units/mL/Units/kg | Standard Deviation 0.0104 |
| FXIII | Incremental Recovery | Week 36 (n = 39) | 0.021 Units/mL/Units/kg | Standard Deviation 0.0056 |
| FXIII | Incremental Recovery | Week 48 (n = 38) | 0.020 Units/mL/Units/kg | Standard Deviation 0.0056 |
Secondary
Peak FXIII Concentration at Steady State
Time frame: At 12, 24, 36 and 48 weeks: at 30 and 60 minutes after the end of the infusion.
Population: The Pharmacokinetic (PK) Population comprised all subjects who received a dose of FXIII Concentrate (Human) during the study and included those who completed the study (defined as having sufficient bioanalytical assessments to calculate reliable estimates of the PK parameters).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FXIII | Peak FXIII Concentration at Steady State | Week 12 (n = 40) | 0.968 Units/mL | Standard Deviation 0.2292 |
| FXIII | Peak FXIII Concentration at Steady State | Week 24 (n = 40) | 1.045 Units/mL | Standard Deviation 0.3825 |
| FXIII | Peak FXIII Concentration at Steady State | Week 36 (n = 41) | 0.962 Units/mL | Standard Deviation 0.2306 |
| FXIII | Peak FXIII Concentration at Steady State | Week 48 (n = 40) | 0.983 Units/mL | Standard Deviation 0.2633 |
Secondary
Time to Peak Concentration
Time frame: At 12, 24, 36 and 48 weeks: immediately before infusion, then at 30 and 60 minutes after the end of the infusion.
Population: The Pharmacokinetic (PK) Population comprised all subjects who received a dose of FXIII Concentrate (Human) during the study and included those who completed the study (defined as having sufficient bioanalytical assessments to calculate reliable estimates of the PK parameters).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FXIII | Time to Peak Concentration | Week 12 (n = 40) | 0.632 Hour | Standard Deviation 0.2296 |
| FXIII | Time to Peak Concentration | Week 24 (n = 40) | 0.615 Hour | Standard Deviation 0.1978 |
| FXIII | Time to Peak Concentration | Week 36 (n = 39) | 0.623 Hour | Standard Deviation 0.235 |
| FXIII | Time to Peak Concentration | Week 48 (n = 40) | 0.636 Hour | Standard Deviation 0.2328 |
Secondary
Trough FXIII Concentration at Steady State
Time frame: At 12, 24, 36 and 48 weeks: immediately before infusion.
Population: The Pharmacokinetic (PK) Population comprised all subjects who received a dose of FXIII Concentrate (Human) during the study and included those who completed the study (defined as having sufficient bioanalytical assessments to calculate reliable estimates of the PK parameters).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FXIII | Trough FXIII Concentration at Steady State | Week 12 (n = 40) | 0.132 Units/mL | Standard Deviation 0.0305 |
| FXIII | Trough FXIII Concentration at Steady State | Week 24 (n = 41) | 0.136 Units/mL | Standard Deviation 0.0362 |
| FXIII | Trough FXIII Concentration at Steady State | Week 36 (n = 41) | 0.130 Units/mL | Standard Deviation 0.0254 |
| FXIII | Trough FXIII Concentration at Steady State | Week 48 (n = 41) | 0.150 Units/mL | Standard Deviation 0.1138 |