Trial Outcomes & Findings for Safety of a Single Intravenous Dose of Recombinant Factor XIII in Children With Congenital FXIII A-subunit Deficiency (NCT NCT01230021)
NCT ID: NCT01230021
Last Updated: 2017-02-24
Results Overview
A measure of the exposure. Blood samples for the PK assessment were drawn pre-dose and up to 30 days after dosing. The PK of FXIII in children was assessed after a single i.v. dose of rFXIII 35 IU/kg.
COMPLETED
PHASE3
6 participants
At pre-dose, 30 minutes, 24 hours, 7, 14, 21 and 30 days after dosing
2017-02-24
Participant Flow
The trial was conducted at five sites located in the UK (2 sites), Israel (1 site) and the US (2 sites).
Between screening and treatment with trial drug the children were assessed for eligibility. If eligible, the children were treated with one single dose of FXIII. The trial was not randomised.
Participant milestones
| Measure |
Recombinant Factor XIII
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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|---|---|
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Overall Study
STARTED
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6
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Overall Study
COMPLETED
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6
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety of a Single Intravenous Dose of Recombinant Factor XIII in Children With Congenital FXIII A-subunit Deficiency
Baseline characteristics by cohort
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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Age, Continuous
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2.67 years
STANDARD_DEVIATION 1.03 • n=39 Participants
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Gender
Female
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3 Participants
n=39 Participants
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Gender
Male
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3 Participants
n=39 Participants
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Ethnicity (NIH/OMB)
Hispanic or Latino
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0 Participants
n=39 Participants
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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6 Participants
n=39 Participants
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Ethnicity (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=39 Participants
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=39 Participants
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Race (NIH/OMB)
Asian
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3 Participants
n=39 Participants
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Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=39 Participants
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Race (NIH/OMB)
Black or African American
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1 Participants
n=39 Participants
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Race (NIH/OMB)
White
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2 Participants
n=39 Participants
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Race (NIH/OMB)
More than one race
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0 Participants
n=39 Participants
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Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=39 Participants
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PRIMARY outcome
Timeframe: At pre-dose, 30 minutes, 24 hours, 7, 14, 21 and 30 days after dosingPopulation: The full analysis set including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
A measure of the exposure. Blood samples for the PK assessment were drawn pre-dose and up to 30 days after dosing. The PK of FXIII in children was assessed after a single i.v. dose of rFXIII 35 IU/kg.
Outcome measures
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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Area Under the Concentration vs. Time Curve (AUC)
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250.25 IU*h/mL
Standard Deviation 31.19
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SECONDARY outcome
Timeframe: From day 0 to day 30Population: The full analysis set including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
A measure of exposure.
Outcome measures
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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Area Under the Concentration vs. Time Curve (AUC0-∞)
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403.18 IU*h/mL
Standard Deviation 92.20
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SECONDARY outcome
Timeframe: At pre-dose, 30 minutes, 24 hours, 7, 14, 21 and 30 days after dosingPopulation: The full analysis set including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
Maximum plasma concentration of the drug reached.
Outcome measures
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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Maximum Plasma Concentration (Cmax) for FXIII
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0.69 U/mL
Standard Deviation 0.14
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SECONDARY outcome
Timeframe: From day 0 to day 30Population: The full analysis set including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
Time point when half of the maximum plasma concentration is reached.
Outcome measures
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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Terminal Half-life (t½)
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378 hours
Interval 236.0 to 596.0
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SECONDARY outcome
Timeframe: From day 0 to day 30Population: The full analysis set including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
The mean residence time (MRT) of a drug in the body and related functions are derived for drugs which are intravenously administered.
Outcome measures
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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Mean Residence Time (MRT)
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729.01 hours
Standard Deviation 265.98
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SECONDARY outcome
Timeframe: From day 0 to day 30Population: The full analysis set including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
The total plasma clearance is a measure of the elimination of a drug from the body. Drugs are excreted primarily by the kidneys into the urine. Clearance is calculated as 'CL=Dose / AUC0-30 days').
Outcome measures
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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Total Plasma Clearance (CL)
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0.10 mL/h/kg
Standard Deviation 0.02
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SECONDARY outcome
Timeframe: At steady statePopulation: The full analysis set including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
Volume of distribution at steady state (Vss) is the theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it is in blood plasma at steady state. Steady state is achieved when all variables are constant in spite of ongoing processes.
Outcome measures
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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Volume of Distribution at Steady State (Vss)
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66.07 mL/kg
Standard Deviation 14.32
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SECONDARY outcome
Timeframe: From day 0 to day 30Population: Safety analysis population including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
Outcome measures
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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Percentage of Subjects With One or More Adverse Events (AEs) Recorded
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33.3 percentage (%) of subjects
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SECONDARY outcome
Timeframe: From day 0 to day 30Population: Safety analysis population including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
Outcome measures
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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Percentage of Subjects With One or More Serious Adverse Events (SAEs)
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0 percentage of subjects
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SECONDARY outcome
Timeframe: At screening and day 30Population: Safety analysis population including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
Outcome measures
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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Percentage of Subjects With Development of Anti-rFXIII Antibodies, Including Inhibitors (Neutralising Antibodies Against Factor XIII)
At screening
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50 percentage of subjects
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Percentage of Subjects With Development of Anti-rFXIII Antibodies, Including Inhibitors (Neutralising Antibodies Against Factor XIII)
Day 30
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50 percentage of subjects
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SECONDARY outcome
Timeframe: Day 0 and at day 30Population: Safety analysis population including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
Outcome measures
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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Coagulation Related Parameters - Fibrinogen
Pre-dose
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3.26 g/L
Standard Deviation 1.04
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Coagulation Related Parameters - Fibrinogen
Post-dose 30 days
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3.46 g/L
Standard Deviation 0.82
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SECONDARY outcome
Timeframe: Day 0 and day 30Population: Safety analysis population including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
Outcome measures
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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Coagulation Related Parameters - Activated Partial Thromboplastin Time (aPTT, Seconds)
Pre-dose
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33.8 Sec
Standard Deviation 9.0
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Coagulation Related Parameters - Activated Partial Thromboplastin Time (aPTT, Seconds)
Post-dose
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30.3 Sec
Standard Deviation 5.6
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SECONDARY outcome
Timeframe: Day 0 and day 30Population: Safety analysis population including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
Outcome measures
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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Coagulation Related Parameters - Prothrombin Time (PT) (Seconds)
Pre-dose
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12.6 Sec
Standard Deviation 0.7
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Coagulation Related Parameters - Prothrombin Time (PT) (Seconds)
Post-dose
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12.1 Sec
Standard Deviation 2.3
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SECONDARY outcome
Timeframe: Day 0 and day 30Population: Safety analysis population including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
Blood samples for clot solubility drawn at each visit (1 hour before and after dose administration). A clot solubility assay was used to screen for FXIII deficiency. The assay is based on the ability of urea to dissolve fibrin clots that have not undergone FXIII-induced stabilization. Normal blood clots generally remain stable for 24 hours or more, while clots in which fibrin molecules have not been cross-linked are soluble within minutes. The outcome of the test is normal (FXIII present; a clot is observed in the test tube) or abnormal (FXIII absent or very low level; no clot in test tube).
Outcome measures
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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Clot Solubility Test (Evaluated as Normal/Abnormal)
Normal (pre-dose)
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4 participants
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Clot Solubility Test (Evaluated as Normal/Abnormal)
Abnormal (pre-dose)
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1 participants
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Clot Solubility Test (Evaluated as Normal/Abnormal)
Not done (pre-dose)
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1 participants
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Clot Solubility Test (Evaluated as Normal/Abnormal)
Normal (post-dose)
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5 participants
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Clot Solubility Test (Evaluated as Normal/Abnormal)
Abnormal (post-dose)
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0 participants
|
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Clot Solubility Test (Evaluated as Normal/Abnormal)
Not done (post-dose)
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1 participants
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SECONDARY outcome
Timeframe: Day 0 and day 30Population: Safety analysis population including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
Outcome measures
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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Vital Signs - Pulse
pre-dose
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95.3 beats/minute
Standard Deviation 14.3
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Vital Signs - Pulse
post-dose
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113.2 beats/minute
Standard Deviation 10.6
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SECONDARY outcome
Timeframe: Day 0 and day 30Population: Safety analysis population including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
Outcome measures
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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Vital Signs - Blood Pressure (Systolic and Diastolic)
Systolic pre-dose
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98.5 mmHg
Standard Deviation 10.9
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Vital Signs - Blood Pressure (Systolic and Diastolic)
Systolic post-dose
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107.0 mmHg
Standard Deviation 13.7
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Vital Signs - Blood Pressure (Systolic and Diastolic)
Diastolic pre-dose
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59.8 mmHg
Standard Deviation 12.1
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Vital Signs - Blood Pressure (Systolic and Diastolic)
Diastolic post-dose
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64.0 mmHg
Standard Deviation 7.6
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SECONDARY outcome
Timeframe: From day 0 to day 30Population: Safety analysis population including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
Outcome measures
| Measure |
Recombinant Factor XIII
n=6 Participants
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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|---|---|
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Physical Examination (Evaluated as Normal/Abnormal)
Normal (post-dose)
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5 participants
|
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Physical Examination (Evaluated as Normal/Abnormal)
Abnormal (post-dose)
|
1 participants
|
|
Physical Examination (Evaluated as Normal/Abnormal)
Normal (pre-dose)
|
6 participants
|
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Physical Examination (Evaluated as Normal/Abnormal)
Abnormal (pre-dose)
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0 participants
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Adverse Events
Recombinant Factor XIII
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Recombinant Factor XIII
n=6 participants at risk
One single dose of 35 IU/kg rFXIII was administered as an intravenous (i.v.) injection to each child. The trial included one screening visit, one treatment visit (including pharmacokinetics (PK) assessments up to 24 hours) and 4 follow-up visits (at 7, 14, 21 and 30 days after dosing). Blood samples for PK assessments were drawn pre-dose and up to 30 days after dosing.
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General disorders
Pyrexia
|
16.7%
1/6 • Number of events 1 • Adverse events were collected and reported during the entire trial period; that is from day 0 (the treatment day) to day 30 (last follow-up visit).
Safety analysis population including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
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Musculoskeletal and connective tissue disorders
Pain In Extremity
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16.7%
1/6 • Number of events 1 • Adverse events were collected and reported during the entire trial period; that is from day 0 (the treatment day) to day 30 (last follow-up visit).
Safety analysis population including all 6 children exposed to FXIII. All 6 children were exposed to one dose of trial product.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Novo Nordisk (NN) reserves the right not to release data until after specified milestones, e.g., finalisation of clinical trial report. This includes the right not to release interim results of clinical trials, as release of such information can invalidate the trial results. At end of trial, one or more manuscripts will be prepared collaboratively between Investigator(s) and NN. NN reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.
- Publication restrictions are in place
Restriction type: OTHER