Factor XIII Deficiency
Conditions
Keywords
Factor XIII
Brief summary
Congenital deficiency of Factor XIII is an extremely rare hereditary disorder associated with potentially life-threatening bleeding. This study will evaluate the safety and recommended (best) amount or level of Factor XIII in a patient's blood. Factor XIII Concentrate (Human) is given to people whose blood is lacking Factor XIII. Factor XIII Concentrate (Human) works by assisting your blood in the usual clotting process, thereby preventing bleeding.
Interventions
BIOLOGICALFXIII Concentrate (Human)
Subjects will receive approximately 40 U/kg of FXIII every 28 days for 3 doses administered as a bolus intravenous (IV) injection at approximately 250 U/minute.
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 that 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) * Positive result at screening for human immunodeficiency virus (HIV) * Serum aspartate transaminase (AST) or serum alanine transaminase (ALT) concentration \>2.5 times the upper limit of normal * Fibrinogen \< lower limit of normal * Active bleeding * 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 * Surgical procedure anticipated during the study period * Suspected inability (e.g., language problems) or unwillingness to comply with study procedures or history of noncompliance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Residence Time | 12 weeks | — |
| Area Under the Curve at Steady State | 12 weeks | — |
| Clearance | 12 weeks | — |
| Volume of Distribution at Steady State | 12 weeks | — |
| Peak FXIII Concentration at Steady State | 12 weeks | — |
| Trough FXIII Concentration at Steady State | 12 weeks | — |
| Time to Peak Concentration | 12 weeks | — |
| Incremental Recovery | 12 weeks | Incremental recovery (U/mL/U/kg) is defined as the maximum (peak) FXIII activity (U/mL) obtained after infusion, per dose of FXIII (U/kg) administered. |
| Terminal Half-life | 12 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Laboratory Safety Parameters | 16 weeks | Number of participants with clinically significant laboratory safety parameter values. The laboratory safety parameters measured included serum chemistries, hematology and urinalysis. |
| Vital Signs | 16 weeks | Number of participants with clinically significant vital signs. The vital signs measured included blood pressure, pulse rate and temperature. Clinically significant changes in vital signs were to be reported as adverse events. |
| Adverse Events | 16 weeks | Number of participants with an adverse event |
Countries
Spain, United States
Participant flow
Pre-assignment details
One subject was not administered FXIII because of the Sponsor's decision. This subject was not included in the analyses.
Participants by arm
| Arm | Count |
|---|---|
| FXIII All subjects treated with Factor FXIII Concentrate (Human) (FXIII) | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Sponsor's decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | FXIII |
|---|---|
| Age Continuous | 24.0 years STANDARD_DEVIATION 12.55 |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 14 |
| serious Total, serious adverse events | 0 / 14 |
Outcome results
Primary
Area Under the Curve at Steady State
Time frame: 12 weeks
Population: The analysis population was the PK population. The PK population comprised all subjects in the safety population who completed the study (defined as having sufficient bioanalytical assessments to calculate reliable estimates of the PK parameters specified).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FXIII | Area Under the Curve at Steady State | 184.0 Units*hr/mL | Standard Deviation 65.78 |
Primary
Clearance
Time frame: 12 weeks
Population: The analysis population was the PK population. The PK population comprised all subjects in the safety population who completed the study (defined as having sufficient bioanalytical assessments to calculate reliable estimates of the PK parameters specified).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FXIII | Clearance | 0.25 mL/hr/kg | Standard Deviation 0.09 |
Primary
Incremental Recovery
Incremental recovery (U/mL/U/kg) is defined as the maximum (peak) FXIII activity (U/mL) obtained after infusion, per dose of FXIII (U/kg) administered.
Time frame: 12 weeks
Population: The analysis population was the PK population. The PK population comprised all subjects in the safety population who completed the study (defined as having sufficient bioanalytical assessments to calculate reliable estimates of the PK parameters specified).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FXIII | Incremental Recovery | 0.02 Units/mL/Units/kg | Standard Deviation 0.01 |
Primary
Mean Residence Time
Time frame: 12 weeks
Population: The analysis population was the PK population. The PK population comprised all subjects in the safety population who completed the study (defined as having sufficient bioanalytical assessments to calculate reliable estimates of the PK parameters specified).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FXIII | Mean Residence Time | 10.0 days | Standard Deviation 3.45 |
Primary
Peak FXIII Concentration at Steady State
Time frame: 12 weeks
Population: The analysis population was the pharmacokinetic (PK) population. The PK population comprised all subjects in the safety population who completed the study (defined as having sufficient bioanalytical assessments to calculate reliable estimates of the PK parameters specified).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FXIII | Peak FXIII Concentration at Steady State | 0.9 Units/mL | Standard Deviation 0.2 |
Primary
Terminal Half-life
Time frame: 12 weeks
Population: The analysis population was the PK population. The PK population comprised all subjects in the safety population who completed the study (defined as having sufficient bioanalytical assessments to calculate reliable estimates of the PK parameters specified).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FXIII | Terminal Half-life | 6.6 days | Standard Deviation 2.29 |
Primary
Time to Peak Concentration
Time frame: 12 weeks
Population: The analysis population was the PK population. The PK population comprised all subjects in the safety population who completed the study (defined as having sufficient bioanalytical assessments to calculate reliable estimates of the PK parameters specified).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FXIII | Time to Peak Concentration | 1.7 hr | Standard Deviation 1.44 |
Primary
Trough FXIII Concentration at Steady State
Time frame: 12 weeks
Population: The analysis population was the PK population. The PK population comprised all subjects in the safety population who completed the study (defined as having sufficient bioanalytical assessments to calculate reliable estimates of the PK parameters specified).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FXIII | Trough FXIII Concentration at Steady State | 0.05 Units/mL | Standard Deviation 0.05 |
Primary
Volume of Distribution at Steady State
Time frame: 12 weeks
Population: The analysis population was the PK population. The PK population comprised all subjects in the safety population who completed the study (defined as having sufficient bioanalytical assessments to calculate reliable estimates of the PK parameters specified).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FXIII | Volume of Distribution at Steady State | 51.1 mL/kg | Standard Deviation 12.61 |
Secondary
Adverse Events
Number of participants with an adverse event
Time frame: 16 weeks
Population: The analysis population was the safety population. The safety population comprised all subjects who received a dose of Factor XIII.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FXIII | Adverse Events | 8 participants |
Secondary
Laboratory Safety Parameters
Number of participants with clinically significant laboratory safety parameter values. The laboratory safety parameters measured included serum chemistries, hematology and urinalysis.
Time frame: 16 weeks
Population: The analysis population was the safety population. The safety population comprised all subjects who received a dose of Factor XIII.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FXIII | Laboratory Safety Parameters | 0 participants |
Secondary
Vital Signs
Number of participants with clinically significant vital signs. The vital signs measured included blood pressure, pulse rate and temperature. Clinically significant changes in vital signs were to be reported as adverse events.
Time frame: 16 weeks
Population: The analysis population was the safety population. The safety population comprised all subjects who received a dose of Factor XIII.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FXIII | Vital Signs | 0 participants |