Trial Outcomes & Findings for Evaluation of Recombinant Factor XIII for Prevention of Bleeding in Patients With FXIII Inherited Deficiency (NCT NCT00713648)
NCT ID: NCT00713648
Last Updated: 2017-02-24
Results Overview
It represents the incidence of bleeding episodes requiring treatment with a FXIII-containing product.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
41 participants
Primary outcome timeframe
For a period of 322 days (approximately one year) comprised of a screening visit (Visit 1), treatment period (Visits 2-15), unscheduled visit and end-of-trial visit (Visit 16).
Results posted on
2017-02-24
Participant Flow
Of a total of 29 initiated trial sites, 23 sites enrolled and dosed at least one patient. The country distribution was (number of actively recruiting sites per country in parenthesis): Austria (1), Canada (1), Finland (1), France (1), Germany (3), Israel (2), Italy (1), Spain (1), Switzerland (1), UK (3) and United States of America (8)
After screening, eligible subjects entered a 4-week run-in period followed by a 52-week recombinant factor XIII (rFXIII) treatment period. Subjects who before entering the trial were receiving regular replacement therapy with a FXIII-containing product were to receive their last standard replacement dose just before the screening visit.
Participant milestones
| Measure |
rFXIII
Subjects received 35 IU/kg rFXIII every 4th week (28±2 days) during a treatment period of 52 weeks. In case of acute bleeding episodes, any additional treatment as per investigator judgment was to be according to local standard practice. Additional doses of rFXIII could therefore not be used to treat such breakthrough bleedings
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|---|---|
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Overall Study
STARTED
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41
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Overall Study
COMPLETED
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33
|
|
Overall Study
NOT COMPLETED
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8
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Reasons for withdrawal
| Measure |
rFXIII
Subjects received 35 IU/kg rFXIII every 4th week (28±2 days) during a treatment period of 52 weeks. In case of acute bleeding episodes, any additional treatment as per investigator judgment was to be according to local standard practice. Additional doses of rFXIII could therefore not be used to treat such breakthrough bleedings
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|---|---|
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Overall Study
Adverse Event
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1
|
|
Overall Study
Unclassified
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2
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Overall Study
According to Protocol
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2
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Overall Study
Development of antibodies
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3
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Baseline Characteristics
Evaluation of Recombinant Factor XIII for Prevention of Bleeding in Patients With FXIII Inherited Deficiency
Baseline characteristics by cohort
| Measure |
rFXIII
n=41 Participants
Subjects received 35 IU/kg rFXIII every 4th week (28±2 days) during a treatment period of 52 weeks. In case of acute bleeding episodes, any additional treatment as per investigator judgment was to be according to local standard practice. Additional doses of rFXIII could therefore not be used to treat such breakthrough bleedings
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|---|---|
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Age, Continuous
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26.4 years
STANDARD_DEVIATION 15.9 • n=5 Participants
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|
Gender
Female
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18 Participants
n=5 Participants
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Gender
Male
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23 Participants
n=5 Participants
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|
Race/Ethnicity, Customized
Black or African American
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2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
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28 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
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5 participants
n=5 Participants
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|
Race/Ethnicity, Customized
Other
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5 participants
n=5 Participants
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|
Race/Ethnicity, Customized
Unknown
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1 participants
n=5 Participants
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PRIMARY outcome
Timeframe: For a period of 322 days (approximately one year) comprised of a screening visit (Visit 1), treatment period (Visits 2-15), unscheduled visit and end-of-trial visit (Visit 16).Population: Full analysis set - consisting of a total of 41 subjects who received at least one dose of trial product.
It represents the incidence of bleeding episodes requiring treatment with a FXIII-containing product.
Outcome measures
| Measure |
rFXIII
n=41 Participants
Subjects received 35 IU/kg rFXIII every 4th week (28±2 days) during a treatment period of 52 weeks. In case of acute bleeding episodes, any additional treatment as per investigator judgment was to be according to local standard practice. Additional doses of rFXIII could therefore not be used to treat such breakthrough bleedings
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|---|---|
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Rate (Number Per Subject Year) of Bleeding Episodes Requiring Treatment With a FXIII Containing Product During the Treatment Period
|
0.138 bleeding episodes per subject per year
Interval 0.0 to 2.0
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SECONDARY outcome
Timeframe: For a period of 322 days (approximately one year) comprised of a screening visit (Visit 1), treatment period (Visits 2-15), unscheduled visit and end-of-trial visit (Visit 16).Population: Full analysis set - consisting of a total of 41 subjects who received at least one dose of trial product. For All Dosing Visits, the participants analyzed (N) are the 'All Visit Subjects Count' i.e. the sum of subject counts across all dosing visits combined.
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 |
rFXIII
n=41 Participants
Subjects received 35 IU/kg rFXIII every 4th week (28±2 days) during a treatment period of 52 weeks. In case of acute bleeding episodes, any additional treatment as per investigator judgment was to be according to local standard practice. Additional doses of rFXIII could therefore not be used to treat such breakthrough bleedings
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|---|---|
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Percentage of Subjects Having a Normal Clot Solubility One Hour After rFXIII Administration and 28 Days After rFXIII Administration for All Dosing Visits
After 1 hour post-dosing (N=444)
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98.2 percentage (%) of subjects
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Percentage of Subjects Having a Normal Clot Solubility One Hour After rFXIII Administration and 28 Days After rFXIII Administration for All Dosing Visits
After 28 days of treatment (N=419)
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91.3 percentage (%) of subjects
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SECONDARY outcome
Timeframe: For a period of 322 days (approximately one year) comprised of a screening visit (Visit 1), treatment period (Visits 2-15), unscheduled visit and end-of-trial visit (Visit 16).Population: Full analysis set - consisting of a total of 41 subjects who received at least one dose of trial product. For All Dosing Visits, the participants analyzed (N) are the 'All Visit Subjects Count' i.e. the sum of subject counts across all dosing visits combined.
Subjects entered a 52-week treatment period of monthly (28±2 days) doses of 35 IU/kg rFXIII. Blood samples for analysis of FXIII activity were drawn at each visit; at dosing visits blood was drawn 1 hour after administration and before administration(corresponding to 28 days after the previous dose). All Dosing Visits are visits where a dose is given (i.e. Visit 2-15 except Visit 3).
Outcome measures
| Measure |
rFXIII
n=41 Participants
Subjects received 35 IU/kg rFXIII every 4th week (28±2 days) during a treatment period of 52 weeks. In case of acute bleeding episodes, any additional treatment as per investigator judgment was to be according to local standard practice. Additional doses of rFXIII could therefore not be used to treat such breakthrough bleedings
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|---|---|
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Level of FXIII Activity One Hour After rFXIII Administration and 28 Days After rFXIII Administration for All Dosing Visits
After 1 hour post-dosing (N=453)
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0.782 U/kg
Standard Deviation 0.342
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Level of FXIII Activity One Hour After rFXIII Administration and 28 Days After rFXIII Administration for All Dosing Visits
After 28 days of treatment (N=459)
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0.189 U/kg
Standard Deviation 0.102
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SECONDARY outcome
Timeframe: For a period of 322 days (approximately one year) comprised of a screening visit (Visit 1), treatment period (Visits 2-15), unscheduled visit and end-of-trial visit (Visit 16).Population: Full analysis set - Subjects who received at least one dose of trial product.
Subjects receiving rFXIII were monitored for the development of binding antibodies. Blood sampling was done before administration of trial product at all visits (Visits 1-16 and unscheduled visit)
Outcome measures
| Measure |
rFXIII
n=41 Participants
Subjects received 35 IU/kg rFXIII every 4th week (28±2 days) during a treatment period of 52 weeks. In case of acute bleeding episodes, any additional treatment as per investigator judgment was to be according to local standard practice. Additional doses of rFXIII could therefore not be used to treat such breakthrough bleedings
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|---|---|
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Number of Subjects With rFXIII Antibody Development
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4 participants
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Adverse Events
rFXIII
Serious events: 6 serious events
Other events: 25 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
rFXIII
n=41 participants at risk
Subjects received 35 IU/kg rFXIII every 4th week (28±2 days) during a treatment period of 52 weeks. In case of acute bleeding episodes, any additional treatment as per investigator judgment was to be according to local standard practice. Additional doses of rFXIII could therefore not be used to treat such breakthrough bleedings
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|---|---|
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Gastrointestinal disorders
Small intestinal obstruction
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2.4%
1/41 • Number of events 1 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
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|
General disorders
Non-cardiac chest pain
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2.4%
1/41 • Number of events 1 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
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|
Infections and infestations
Diverticulitis
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2.4%
1/41 • Number of events 1 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
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|
Injury, poisoning and procedural complications
Road traffic accident
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2.4%
1/41 • Number of events 1 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
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Investigations
Antibody test positive
|
7.3%
3/41 • Number of events 3 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
|
|
Nervous system disorders
Headache
|
2.4%
1/41 • Number of events 1 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
|
Other adverse events
| Measure |
rFXIII
n=41 participants at risk
Subjects received 35 IU/kg rFXIII every 4th week (28±2 days) during a treatment period of 52 weeks. In case of acute bleeding episodes, any additional treatment as per investigator judgment was to be according to local standard practice. Additional doses of rFXIII could therefore not be used to treat such breakthrough bleedings
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
7.3%
3/41 • Number of events 3 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
|
|
Gastrointestinal disorders
Toothache
|
7.3%
3/41 • Number of events 5 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
|
|
Gastrointestinal disorders
Vomiting
|
7.3%
3/41 • Number of events 3 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
|
|
General disorders
Pyrexia
|
17.1%
7/41 • Number of events 7 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
|
|
Infections and infestations
Influenza
|
9.8%
4/41 • Number of events 4 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
|
|
Infections and infestations
Nasopharyngitis
|
19.5%
8/41 • Number of events 11 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
|
|
Infections and infestations
Urinary tract infection
|
7.3%
3/41 • Number of events 3 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
|
|
Injury, poisoning and procedural complications
Excoriation
|
7.3%
3/41 • Number of events 3 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
|
|
Injury, poisoning and procedural complications
Incorrect dose administered
|
9.8%
4/41 • Number of events 11 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
12.2%
5/41 • Number of events 5 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
9.8%
4/41 • Number of events 4 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
|
|
Nervous system disorders
Headache
|
26.8%
11/41 • Number of events 20 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.3%
3/41 • Number of events 4 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
12.2%
5/41 • Number of events 6 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
9.8%
4/41 • Number of events 6 • Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
All AEs observed by the investigator or reported spontaneously by the subjects, were recorded by the investigator at each contact with the site (visit or telephone, excluding safety visits, where the subject was not seeing the Investigator or his staff (e.g.visits to the laboratory))
|
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