Safety and Efficacy of Monthly Replacement Therapy With Recombinant Factor XIII (rFXIII) in Paediatric Subjects With Congenital Factor XIII A-subunit Deficiency

A Multi-Centre, Multinational, Open-Label, Single-Arm and Multiple Dosing Trial on Safety and Efficacy of Monthly Replacement Therapy With Recombinant Factor XIII (rFXIII) in Paediatric Subjects With Congenital Factor XIII A-subunit Deficiency. Safety Extension Trial to F13CD-3760

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01253811

Acronym

mentor™5

Enrollment

Registered

2010-12-03

Start date

2011-01-31

Completion date

2015-03-31

Last updated

2016-06-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Congenital Bleeding Disorder, Congenital FXIII Deficiency

Brief summary

This trial will be conducted in Asia, Europe and the United States of America (USA). The aim of this clinical trial is to investigate long-term safety of rFXIII when administered for prevention of bleeding episodes in children aged between 1 and 6 years with congenital FXIII A-subunit deficiency. This trial is an extension to trial F13CD-3760 (mentor™4, NCT01230021). If applicable the trial will be extended up to maximum 3 years dependent on when recombinant factor XIII will be commercially available in subject's respective country for use in children of 1-6 years of age.

Interventions

DRUGcatridecacog

Intravenous injection of a single dose of recombinant factor XIII, 35 IU/kg body weight every 4th week

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

1 Years to 6 Years

Healthy volunteers

Inclusion criteria

* Completed participation in trial F13CD-3760 (NCT01230021)

Exclusion criteria

* Known or suspected hypersensitivity to trial product or related products * Known history of development of inhibitors against FXIII (factor XIII) * Hereditary or acquired coagulation disorder other than FXIII congenital deficiency * Platelet count (thrombocytes) less than 50X10e9 / L * Previous history of autoimmune disorder involving autoantibodies e.g., systemic lupus erythematosus * Previous history of arterial or venous thromboembolic events e.g., cerebrovascular accident or deep vein thrombosis * Any disease or condition which, judged by the trial physician, could imply a potential hazard to the subject, interfere with the trial participation or trial outcome including renal and/or liver dysfunction

Design outcomes

Primary

Measure	Time frame	Description
Number of Treatment Emergent (Serious and Non-serious) Adverse Events	Week 0 to end of trial visit (week 173) for a minimum period of 52 weeks.	An adverse event was described as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, and which does not necessarily have a causal relationship with this treatment. Treatment emergent adverse events (serious and non-serious), defined as adverse events occurring from first trial product administration to the end of the subject's participation in the trial.

Secondary

Measure	Time frame	Description
Clinical Laboratory Assessments: Biochemistry: Creatinine	Every 6th month, from week 24 to end of trial visit (week 173).	Clinical laboratory assessments for creatinine at week 24 to end of trial visit.
Clinical Laboratory Assessments: Biochemistry: Urea	Every 6th month, week 24 to end of trial visit (week 173).	Clinical laboratory assessments for urea at week 24 to end ot trial visit.
Clinical Laboratory Assessments: Biochemistry: Alanine Aminotransferase (ALAT)	Every 6th month, from week 24 to end of trial visit (week 173).	Clinical laboratory assessments for ALAT at week 24 to end of trial visit.
Clinical Laboratory Assessments: Biochemistry: Aspartate Aminotransferase (ASAT)	Every 6th month, from week 24 to end of trial visit (week 173).	Clinical laboratory assessments for ASAT at week 24 to end of trial visit.
Clinical Laboratory Assessments: Haematology: Haemoglobin	Every 6th month, from week 0 to end of trial visit (week 173).	Clinical values for haemoglobin collected from week 0 to end of trial visit.
Clinical Laboratory Assessments: Haematology: Leucocytes	Every 6th month, from week 0 to end of trial visit (week 173).	Clinical laboratory values for leucocytes collected from week 0 to end of trial visit.
Clinical Laboratory Assessments: Haematology: Thrombocytes	Every 6th month, from week 0 to end of trial visit (week 173).	Clinical laboratory values for thrombocytes collected from week 0 to end of trial visit.
Percentage of Subjects With Development of Anti-rFXIII Antibodies, Including Inhibitors.	Week 0 to end of trial visit (week 173).	All subjects who received rFXIII were monitored for the frequency of development of anti-rFXIII antibodies. 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.
Clinical Laboratory Assessments: Haematology: Haematocrit	Every 6th month, from week 0 to end of trial visit (week 173).	Clinical laboratory values for haematocrit collected from week 0 to end of trial visit.
Physical Examinations	Week 0 to end of trial visit (week 173).	Number of subjects in percentage with changes in values of physical examinations from week 0 to end of trial visit were collected.
Vital Signs: Systolic BP (Blood Pressure)	Week 0 to end of trial visit (week 173).	Values collected for systolic BP from week 0 to end of trial visit.
Vital Signs: Diastolic BP (Blood Pressure)	Week 0 to end of trial visit (week 173).	Values collected for diastolic BP from week 0 to end of trial visit.
Vital Signs: Pulse	Week 0 to end of trial visit (week 173).	Values collected for pulse from week 0 to end of trial visit.
Rate (Number Per Subject Year) of All Bleeding Episodes Requiring Treatment With a FXIII Containing Product Other Than Recombinant Factor XIII.	Weeks 0 to end of trial visit (week 173).	The rate (number per subject year) of all spontaneous, traumatic and intracranial bleeding episodes requiring treatment with FXIII-containing products during the rFXIII treatment period was assessed for treatment period.
Clinical Laboratory Assessments: Haematology: Erythrocytes	Every 6th month, from week 0 to end of trial visit (week 173).	Clinical laboratory values for erythrocytes collected from week 0 to end of trial visit.

Countries

Israel, United Kingdom, United States

Participant flow

Recruitment details

The trial was conducted at 5 sites in 3 countries as follows: Israel (IS): 1 site; United Kingdom (UK): 2 sites; and United States (US): 2 sites.

Pre-assignment details

Subjects who completed the F13CD-3760 (NCT01230021) trial were eligible to get enrolled in this trial.

Participants by arm

Arm	Count
rFXIII 35 IU/kg Subjects received 35 IU/kg recombinant factor XIII (rFXIII) slow intravenous (i.v.) administered every 4 weeks (28 ± 2 days) as preventive treatment of bleeding episodes. Each dose was reconstituted, diluted with saline and injection was given at a rate not exceeding 1-2 mL min-1. This dose was identical to the dose administered in the trial F13CD-3760. The correct dosing was calculated based on subject's body weight. Subjects received rFXIII either at the clinic during the first year or as home treatment after one year, and only if allowed, according to local regulations.	6
Total	6

Arm

Count

rFXIII 35 IU/kg

Subjects received 35 IU/kg recombinant factor XIII (rFXIII) slow intravenous (i.v.) administered every 4 weeks (28 ± 2 days) as preventive treatment of bleeding episodes. Each dose was reconstituted, diluted with saline and injection was given at a rate not exceeding 1-2 mL min-1. This dose was identical to the dose administered in the trial F13CD-3760. The correct dosing was calculated based on subject's body weight. Subjects received rFXIII either at the clinic during the first year or as home treatment after one year, and only if allowed, according to local regulations.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Withdrawal criteria	1

Baseline characteristics

Characteristic	rFXIII 35 IU/kg
Age, Continuous	3.0 years STANDARD_DEVIATION 1.3
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	3 Participants
Race (NIH/OMB) Black or African American	1 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	2 Participants
Sex: Female, Male Female	3 Participants
Sex: Female, Male Male	3 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	6 / 6
serious Total, serious adverse events	1 / 6

Outcome results

Primary

Number of Treatment Emergent (Serious and Non-serious) Adverse Events

An adverse event was described as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, and which does not necessarily have a causal relationship with this treatment. Treatment emergent adverse events (serious and non-serious), defined as adverse events occurring from first trial product administration to the end of the subject's participation in the trial.

Time frame: Week 0 to end of trial visit (week 173) for a minimum period of 52 weeks.

Population: The safety analysis set included all subjects who received at least one dose of the trial product.

Arm	Measure	Group	Value (NUMBER)
rFXIII 35 IU/kg	Number of Treatment Emergent (Serious and Non-serious) Adverse Events	All adverse events	100 number of events
rFXIII 35 IU/kg	Number of Treatment Emergent (Serious and Non-serious) Adverse Events	Serious adverse events	2 number of events
rFXIII 35 IU/kg	Number of Treatment Emergent (Serious and Non-serious) Adverse Events	Non-serious adverse events	98 number of events

Secondary

Clinical Laboratory Assessments: Biochemistry: Alanine Aminotransferase (ALAT)

Clinical laboratory assessments for ALAT at week 24 to end of trial visit.

Time frame: Every 6th month, from week 24 to end of trial visit (week 173).

Population: The safety analysis set included all subjects who received at least one dose of the trial product.

Arm	Measure	Group	Value (MEAN)	Dispersion
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Alanine Aminotransferase (ALAT)	Week 24 (pre-dose), N=4	17.75 IU/L	Standard Deviation 5.85
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Alanine Aminotransferase (ALAT)	Week 48 (pre-dose), N=5	16.20 IU/L	Standard Deviation 2.39
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Alanine Aminotransferase (ALAT)	Week 72 (pre-dose), N=5	16.40 IU/L	Standard Deviation 4.93
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Alanine Aminotransferase (ALAT)	Week 96 (pre-dose), N=4	12.50 IU/L	Standard Deviation 3.7
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Alanine Aminotransferase (ALAT)	Week 120 (pre-dose), N=3	21.33 IU/L	Standard Deviation 12.1
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Alanine Aminotransferase (ALAT)	Week 144 (pre-dose), N=2	17.00 IU/L	Standard Deviation 1.41
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Alanine Aminotransferase (ALAT)	Week 168 (pre-dose), N=1	14.00 IU/L	Standard Deviation 0
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Alanine Aminotransferase (ALAT)	End of trial (week 173) pre-dose, N=5	16.00 IU/L	Standard Deviation 3.94

Secondary

Clinical Laboratory Assessments: Biochemistry: Aspartate Aminotransferase (ASAT)

Clinical laboratory assessments for ASAT at week 24 to end of trial visit.

Time frame: Every 6th month, from week 24 to end of trial visit (week 173).

Population: The safety analysis set included all subjects who received at least one dose of the trial product.

Arm	Measure	Group	Value (MEAN)	Dispersion
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Aspartate Aminotransferase (ASAT)	Week 24 (pre-dose), N=4	30.75 IU/L	Standard Deviation 5.68
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Aspartate Aminotransferase (ASAT)	Week 48 (pre-dose), N=5	38.20 IU/L	Standard Deviation 10.99
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Aspartate Aminotransferase (ASAT)	Week 72 (pre-dose), N=5	31.20 IU/L	Standard Deviation 8.11
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Aspartate Aminotransferase (ASAT)	Week 96 (pre-dose), N=4	26.25 IU/L	Standard Deviation 1.71
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Aspartate Aminotransferase (ASAT)	Week 120 (pre-dose), N=3	27.00 IU/L	Standard Deviation 3
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Aspartate Aminotransferase (ASAT)	End of trial (week 173) pre-dose, N=5	28.00 IU/L	Standard Deviation 3.61
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Aspartate Aminotransferase (ASAT)	Week 144(pre-dose), N=2	26.00 IU/L	Standard Deviation 1.41
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Aspartate Aminotransferase (ASAT)	Week 168 (pre-dose), N=1	25.00 IU/L	Standard Deviation 0

Secondary

Clinical Laboratory Assessments: Biochemistry: Creatinine

Clinical laboratory assessments for creatinine at week 24 to end of trial visit.

Time frame: Every 6th month, from week 24 to end of trial visit (week 173).

Population: The safety analysis set included all subjects who received at least one dose of the trial product.

Arm	Measure	Group	Value (MEAN)	Dispersion
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Creatinine	Week 24 (pre-dose), N=5	30.20 mmol/L	Standard Deviation 8.23
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Creatinine	Week 48 (pre-dose), N=5	28.00 mmol/L	Standard Deviation 6.16
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Creatinine	Week 72 (pre-dose), N=6	28.67 mmol/L	Standard Deviation 5.13
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Creatinine	Week 96 (pre-dose), N=5	37.00 mmol/L	Standard Deviation 4.74
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Creatinine	Week 120 (pre-dose), N=4	31.50 mmol/L	Standard Deviation 5.92
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Creatinine	Week 144 (pre-dose), N=3	31.00 mmol/L	Standard Deviation 6
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Creatinine	Week 168 (pre-dose), N=1	55.00 mmol/L	Standard Deviation 0
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Creatinine	End of trial (week 173) pre-dose, N= 6	35.17 mmol/L	Standard Deviation 9.79

Secondary

Clinical Laboratory Assessments: Biochemistry: Urea

Clinical laboratory assessments for urea at week 24 to end ot trial visit.

Time frame: Every 6th month, week 24 to end of trial visit (week 173).

Population: The safety analysis set included all subjects who received at least one dose of the trial product.

Arm	Measure	Group	Value (MEAN)	Dispersion
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Urea	Week 144 (pre-dose), N=3	4.52 mmol/L	Standard Deviation 1.35
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Urea	Week 168 (pre-dose), N=1	5.00 mmol/L	Standard Deviation 0
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Urea	End of trial (week 173) pre-dose, N= 6	4.28 mmol/L	Standard Deviation 0.84
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Urea	Week 24 (pre-dose), N=5	5.50 mmol/L	Standard Deviation 1.63
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Urea	Week 48 (pre-dose), N=5	4.00 mmol/L	Standard Deviation 1.22
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Urea	Week 72 (pre-dose), N=6	3.99 mmol/L	Standard Deviation 0.69
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Urea	Week 96 (pre-dose), N=5	4.50 mmol/L	Standard Deviation 1.14
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Biochemistry: Urea	Week 120 (pre-dose), N=4	3.48 mmol/L	Standard Deviation 0.73

Secondary

Clinical Laboratory Assessments: Haematology: Erythrocytes

Clinical laboratory values for erythrocytes collected from week 0 to end of trial visit.

Time frame: Every 6th month, from week 0 to end of trial visit (week 173).

Population: The safety analysis set included all subjects who received at least one dose of the trial product.

Arm	Measure	Group	Value (MEAN)	Dispersion
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Erythrocytes	Week 0 (pre-dose), N=6	4.863 10^12 cells/L	Standard Deviation 0.43
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Erythrocytes	Week 24 (pre-dose), N=4	4.745 10^12 cells/L	Standard Deviation 0.18
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Erythrocytes	Week 48 (pre-dose), N=3	4.587 10^12 cells/L	Standard Deviation 0.12
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Erythrocytes	Week 72 (pre-dose), N=4	4.505 10^12 cells/L	Standard Deviation 0.22
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Erythrocytes	Week 96 (pre-dose), N=4	4.628 10^12 cells/L	Standard Deviation 0.26
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Erythrocytes	Week 120 (pre-dose), N=3	4.247 10^12 cells/L	Standard Deviation 1.19
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Erythrocytes	Week 144 (pre-dose), N=3	4.627 10^12 cells/L	Standard Deviation 0.11
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Erythrocytes	Week 168 (pre-dose), N=2	4.875 10^12 cells/L	Standard Deviation 0.11
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Erythrocytes	End of trial (week 173), N=6	4.662 10^12 cells/L	Standard Deviation 0.21

Secondary

Clinical Laboratory Assessments: Haematology: Haematocrit

Clinical laboratory values for haematocrit collected from week 0 to end of trial visit.

Time frame: Every 6th month, from week 0 to end of trial visit (week 173).

Population: The safety analysis set included all subjects who received at least one dose of the trial product.

Arm	Measure	Group	Value (MEAN)	Dispersion
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haematocrit	Week 0 (pre-dose), N=6	35.07 percentage of red blood cells	Standard Deviation 0.99
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haematocrit	Week 24 (pre-dose), N=4	36.05 percentage of red blood cells	Standard Deviation 1.9
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haematocrit	Week 48 (pre-dose), N=3	32.83 percentage of red blood cells	Standard Deviation 1.76
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haematocrit	Week 72 (pre-dose), N=4	34.80 percentage of red blood cells	Standard Deviation 2.49
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haematocrit	Week 96 (pre-dose), N=4	36.85 percentage of red blood cells	Standard Deviation 1.07
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haematocrit	Week 120 (pre-dose), N=3	32.83 percentage of red blood cells	Standard Deviation 8.61
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haematocrit	Week 144 (pre-dose), N=3	36.6 percentage of red blood cells	Standard Deviation 3.44
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haematocrit	Week 168 (pre-dose), N=2	36.40 percentage of red blood cells	Standard Deviation 2.26
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haematocrit	End of trial (week 173), N=6	37.45 percentage of red blood cells	Standard Deviation 3.22

Secondary

Clinical Laboratory Assessments: Haematology: Haemoglobin

Clinical values for haemoglobin collected from week 0 to end of trial visit.

Time frame: Every 6th month, from week 0 to end of trial visit (week 173).

Population: The safety analysis set included all subjects who received at least one dose of the trial product.

Arm	Measure	Group	Value (MEAN)	Dispersion
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haemoglobin	Week 0 (pre-dose), N=6	7.366 mmol/L	Standard Deviation 0.25
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haemoglobin	Week 24 (pre-dose), N=4	7.624 mmol/L	Standard Deviation 0.19
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haemoglobin	Week 48 (pre-dose), N=3	7.138 mmol/L	Standard Deviation 0.31
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haemoglobin	Week 72 (pre-dose), N=3	7.262 mmol/L	Standard Deviation 0.65
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haemoglobin	Week 96 (pre-dose), N=3	7.635 mmol/L	Standard Deviation 0.27
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haemoglobin	Week 120 (pre-dose), N=3	7.821 mmol/L	Standard Deviation 0.38
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haemoglobin	Week 144 (pre-dose), N=3	7.717 mmol/L	Standard Deviation 0.7
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haemoglobin	Week 168 (pre-dose), N=2	7.759 mmol/L	Standard Deviation 0.53
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Haemoglobin	End of trial (week 173) pre-dose, N=6	8.048 mmol/L	Standard Deviation 0.45

Secondary

Clinical Laboratory Assessments: Haematology: Leucocytes

Clinical laboratory values for leucocytes collected from week 0 to end of trial visit.

Time frame: Every 6th month, from week 0 to end of trial visit (week 173).

Population: The safety analysis set included all subjects who received at least one dose of the trial product.

Arm	Measure	Group	Value (MEAN)	Dispersion
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Leucocytes	Week 0 (pre-dose), N=6	8.367 10^9 cells/L	Standard Deviation 2.2
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Leucocytes	Week 24 (pre-dose), N=4	7.373 10^9 cells/L	Standard Deviation 1.88
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Leucocytes	Week 48 (pre-dose), N=3	5.387 10^9 cells/L	Standard Deviation 1.06
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Leucocytes	Week 72 (pre-dose), N=4	5.863 10^9 cells/L	Standard Deviation 1.96
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Leucocytes	Week 96 (pre-dose), N=4	6.643 10^9 cells/L	Standard Deviation 1.89
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Leucocytes	Week 120(pre-dose), N=3	5.027 10^9 cells/L	Standard Deviation 2.12
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Leucocytes	Week 144(pre-dose), N=3	4.850 10^9 cells/L	Standard Deviation 3
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Leucocytes	Week 168(pre-dose), N=2	4.275 10^9 cells/L	Standard Deviation 2.65
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Leucocytes	End of trial (week 173) pre-dose, N=6	7.605 10^9 cells/L	Standard Deviation 1.25

Secondary

Clinical Laboratory Assessments: Haematology: Thrombocytes

Clinical laboratory values for thrombocytes collected from week 0 to end of trial visit.

Time frame: Every 6th month, from week 0 to end of trial visit (week 173).

Population: The safety analysis set included all subjects who received at least one dose of the trial product.

Arm	Measure	Group	Value (MEAN)	Dispersion
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Thrombocytes	Week 0 (pre-dose), N=6	316.3 10^9 cells/L	Standard Deviation 50.75
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Thrombocytes	Week 24 (pre-dose), N=4	296.0 10^9 cells/L	Standard Deviation 54.17
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Thrombocytes	Week 48 (pre-dose), N=3	277.0 10^9 cells/L	Standard Deviation 93.72
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Thrombocytes	Week 72 (pre-dose), N=4	283.3 10^9 cells/L	Standard Deviation 41.63
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Thrombocytes	Week 96 (pre-dose), N=4	332.3 10^9 cells/L	Standard Deviation 107.3
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Thrombocytes	Week 120 (pre-dose), N=3	269.7 10^9 cells/L	Standard Deviation 102.2
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Thrombocytes	Week 144 (pre-dose), N=3	324.3 10^9 cells/L	Standard Deviation 44.64
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Thrombocytes	Week 168 (pre-dose), N=2	307.0 10^9 cells/L	Standard Deviation 15.56
rFXIII 35 IU/kg	Clinical Laboratory Assessments: Haematology: Thrombocytes	End of trial (week 173) pre-dose, N=6	321.3 10^9 cells/L	Standard Deviation 60.45

Secondary

Percentage of Subjects With Development of Anti-rFXIII Antibodies, Including Inhibitors.

All subjects who received rFXIII were monitored for the frequency of development of anti-rFXIII antibodies. 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.

Time frame: Week 0 to end of trial visit (week 173).

Population: The SAS included all subjects who received at least one dose of the trial product. There were no antibodies against rFXIII detected in any patient during the trial.

Arm	Measure	Value (NUMBER)
rFXIII 35 IU/kg	Percentage of Subjects With Development of Anti-rFXIII Antibodies, Including Inhibitors.	0 percentage of subjects

Secondary

Physical Examinations

Number of subjects in percentage with changes in values of physical examinations from week 0 to end of trial visit were collected.

Time frame: Week 0 to end of trial visit (week 173).

Population: The safety analysis set included all subjects who received at least one dose of the trial product. Two abnormal physical examination findings related to skin and musculo-skeletal system were assessed as clinically significant by the investigator during the trial.

Arm	Measure	Group	Value (NUMBER)
rFXIII 35 IU/kg	Physical Examinations	Skin	3 percentage of subjects
rFXIII 35 IU/kg	Physical Examinations	Musculo-skeletal system	1 percentage of subjects

Secondary

Rate (Number Per Subject Year) of All Bleeding Episodes Requiring Treatment With a FXIII Containing Product Other Than Recombinant Factor XIII.

The rate (number per subject year) of all spontaneous, traumatic and intracranial bleeding episodes requiring treatment with FXIII-containing products during the rFXIII treatment period was assessed for treatment period.

Time frame: Weeks 0 to end of trial visit (week 173).

Population: There were no bleeding episodes requiring treatment with a haemostatic agent (rFXIII) during the trial, which included subjects from full analysis set who received at least one dose of the trial product.

Secondary

Vital Signs: Diastolic BP (Blood Pressure)

Values collected for diastolic BP from week 0 to end of trial visit.

Time frame: Week 0 to end of trial visit (week 173).

Population: The safety analysis set one dose of the trial product.

Arm	Measure	Group	Value (MEAN)	Dispersion
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 0, N=6	64.0 mmHg	Standard Deviation 7.6
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 4, N=6	62.7 mmHg	Standard Deviation 11.4
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 8, N=6	58.3 mmHg	Standard Deviation 19.1
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 12, N=6	57.5 mmHg	Standard Deviation 7.9
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 16, N=6	52.0 mmHg	Standard Deviation 3.3
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 20, N=6	65.2 mmHg	Standard Deviation 6.5
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 24, N=6	64.0 mmHg	Standard Deviation 4.4
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 28, N=6	58.3 mmHg	Standard Deviation 10.4
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 48, N=6	64.7 mmHg	Standard Deviation 10.9
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 60, N=5	69.4 mmHg	Standard Deviation 10.9
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 72, N=6	58.2 mmHg	Standard Deviation 4.6
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 84, N=6	57.5 mmHg	Standard Deviation 8.1
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 120, N=4	62.0 mmHg	Standard Deviation 3.4
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 132, N=4	55.8 mmHg	Standard Deviation 8.4
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 144, N=3	52.0 mmHg	Standard Deviation 9.2
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 156, N=3	57.7 mmHg	Standard Deviation 6.7
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 168, N=2	53.5 mmHg	Standard Deviation 2.1
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	End of trial (week 173), N=6	56.2 mmHg	Standard Deviation 5.5
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 32, N=6	61.7 mmHg	Standard Deviation 16.4
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 36, N=6	66.2 mmHg	Standard Deviation 11.1
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 40, N=6	62.5 mmHg	Standard Deviation 6.4
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 44, N=6	60.3 mmHg	Standard Deviation 7.3
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 96, N=5	62.0 mmHg	Standard Deviation 6.3
rFXIII 35 IU/kg	Vital Signs: Diastolic BP (Blood Pressure)	Week 108, N=5	57.6 mmHg	Standard Deviation 10.4

Secondary

Vital Signs: Pulse

Values collected for pulse from week 0 to end of trial visit.

Time frame: Week 0 to end of trial visit (week 173).

Population: The safety analysis included all subjects who received at least one dose of the trial product.

Arm	Measure	Group	Value (MEAN)	Dispersion
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 0, N=6	113.2 beats/minute	Standard Deviation 10.6
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 4, N=6	97.7 beats/minute	Standard Deviation 16.9
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 8, N=6	106.2 beats/minute	Standard Deviation 4.6
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 12, N=6	104.5 beats/minute	Standard Deviation 7.3
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 20, N=6	105.3 beats/minute	Standard Deviation 19.7
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 24, N=6	103.7 beats/minute	Standard Deviation 6.4
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 28, N=6	102.2 beats/minute	Standard Deviation 9.3
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 32, N=6	108.3 beats/minute	Standard Deviation 20.5
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 36, N=6	95.5 beats/minute	Standard Deviation 22.2
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 40, N=6	93.2 beats/minute	Standard Deviation 19.5
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 44, N=6	95.5 beats/minute	Standard Deviation 23.2
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 60, N=5	109.0 beats/minute	Standard Deviation 15.1
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 72, N=6	100.8 beats/minute	Standard Deviation 11.4
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 84, N=6	99.3 beats/minute	Standard Deviation 7.9
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 96, N=4	96.5 beats/minute	Standard Deviation 16.2
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 108, N=5	98.4 beats/minute	Standard Deviation 18
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 120, N=4	85.0 beats/minute	Standard Deviation 16.4
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 132, N=4	86.3 beats/minute	Standard Deviation 16.7
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 144, N=3	88.0 beats/minute	Standard Deviation 11.1
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 156, N=3	100.7 beats/minute	Standard Deviation 11
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 168, N=2	92.0 beats/minute	Standard Deviation 9.9
rFXIII 35 IU/kg	Vital Signs: Pulse	End of trial (week 173), N=6	94.0 beats/minute	Standard Deviation 16.8
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 48, N=6	100.5 beats/minute	Standard Deviation 7.9
rFXIII 35 IU/kg	Vital Signs: Pulse	Week 16, N=6	109.8 beats/minute	Standard Deviation 9.8

Secondary

Vital Signs: Systolic BP (Blood Pressure)

Values collected for systolic BP from week 0 to end of trial visit.

Time frame: Week 0 to end of trial visit (week 173).

Population: The safety analysis set included all subjects who received at least one dose of the trial product.

Arm	Measure	Group	Value (MEAN)	Dispersion
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 0, N=6	107.0 mmHg	Standard Deviation 13.7
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 4, N=6	101.0 mmHg	Standard Deviation 8.4
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 84, N=6	100.7 mmHg	Standard Deviation 10.7
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 96, N=5	101.2 mmHg	Standard Deviation 4.8
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 108, N=5	109.6 mmHg	Standard Deviation 10.9
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 120, N=4	107.0 mmHg	Standard Deviation 7
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 132, N=4	99.3 mmHg	Standard Deviation 6.2
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 144, N=3	101.7 mmHg	Standard Deviation 7.8
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 156, N=3	110.7 mmHg	Standard Deviation 7
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 168, N=2	107.0 mmHg	Standard Deviation 7.1
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	End of trial (week 173), N=6	96.5 mmHg	Standard Deviation 4.8
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 8, N=6	99.0 mmHg	Standard Deviation 9.4
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 12, N=6	106.3 mmHg	Standard Deviation 9.4
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 16, N=6	106.0 mmHg	Standard Deviation 4.1
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 20, N=6	100.7 mmHg	Standard Deviation 10
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 24, N=6	112.0 mmHg	Standard Deviation 12.6
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 28, N=6	101.3 mmHg	Standard Deviation 11.4
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 32, N=6	103.7 mmHg	Standard Deviation 20.6
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 36, N=6	102.3 mmHg	Standard Deviation 11.9
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 40, N=6	99.7 mmHg	Standard Deviation 8.3
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 44, N=6	99.7 mmHg	Standard Deviation 13
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 48, N=6	103.5 mmHg	Standard Deviation 19.4
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 60, N=5	105.4 mmHg	Standard Deviation 7.8
rFXIII 35 IU/kg	Vital Signs: Systolic BP (Blood Pressure)	Week 72, N=6	101.7 mmHg	Standard Deviation 7.3

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Safety and Efficacy of Monthly Replacement Therapy With Recombinant Factor XIII (rFXIII) in Paediatric Subjects With Congenital Factor XIII A-subunit Deficiency

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Number of Treatment Emergent (Serious and Non-serious) Adverse Events

Clinical Laboratory Assessments: Biochemistry: Alanine Aminotransferase (ALAT)

Clinical Laboratory Assessments: Biochemistry: Aspartate Aminotransferase (ASAT)

Clinical Laboratory Assessments: Biochemistry: Creatinine

Clinical Laboratory Assessments: Biochemistry: Urea

Clinical Laboratory Assessments: Haematology: Erythrocytes

Clinical Laboratory Assessments: Haematology: Haematocrit

Clinical Laboratory Assessments: Haematology: Haemoglobin

Clinical Laboratory Assessments: Haematology: Leucocytes

Clinical Laboratory Assessments: Haematology: Thrombocytes

Percentage of Subjects With Development of Anti-rFXIII Antibodies, Including Inhibitors.

Physical Examinations

Rate (Number Per Subject Year) of All Bleeding Episodes Requiring Treatment With a FXIII Containing Product Other Than Recombinant Factor XIII.

Vital Signs: Diastolic BP (Blood Pressure)

Vital Signs: Pulse

Vital Signs: Systolic BP (Blood Pressure)