Clinical Trial Results:
A Multi-Centre, Open-Label, Single-Arm and Multiple Dosing Trial on Efficacy and Safety of Monthly Replacement Therapy with Recombinant Factor XIII (rFXIII) in Subjects with Congenital Factor XIII Deficiency.
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Summary
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EudraCT number |
2006-003148-51 |
Trial protocol |
GB FR DE AT ES FI IT |
Global end of trial date |
15 Apr 2010
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Results information
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Results version number |
v1 |
This version publication date |
16 Mar 2016
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First version publication date |
21 Jul 2015
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
F13CD-1725
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00713648 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novo Nordisk A/S
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Sponsor organisation address |
Novo Allé, Bagsvaerd, Denmark, 2880
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Public contact |
Global Clinical registry (GCR, 1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
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Scientific contact |
Global Clinical registry (GCR, 1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000185-PIP01-08 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 Nov 2010
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Apr 2010
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of monthly replacement therapy with rFXIII on prevention of bleeding episodes in subjects with congenital FXIII deficiency.
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Protection of trial subjects |
The trial was conducted in accordance with the Declaration of Helsinki and ICH Good Clinical Practice.
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Background therapy |
Subjects who had received regular replacement therapy before entering the trial, were to have initiated this treatment at least 6 months prior to screening. | ||
Evidence for comparator |
Not applicable. | ||
Actual start date of recruitment |
18 Aug 2008
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 2
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Country: Number of subjects enrolled |
United Kingdom: 5
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Country: Number of subjects enrolled |
Austria: 1
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Country: Number of subjects enrolled |
Finland: 2
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Country: Number of subjects enrolled |
France: 1
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Country: Number of subjects enrolled |
Germany: 6
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Country: Number of subjects enrolled |
Italy: 1
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Country: Number of subjects enrolled |
Canada: 3
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Country: Number of subjects enrolled |
Israel: 8
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Country: Number of subjects enrolled |
United States: 10
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Country: Number of subjects enrolled |
Switzerland: 2
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Worldwide total number of subjects |
41
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EEA total number of subjects |
18
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
9
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Adolescents (12-17 years) |
6
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Adults (18-64 years) |
26
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
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). | ||||||||||||||||
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Pre-assignment
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Screening details |
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. | ||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||
Blinding implementation details |
Not applicable.
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Arms
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Arm title
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rFXIII | ||||||||||||||||
Arm description |
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. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Recombinant Factor XIII
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Investigational medicinal product code |
F13CD
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Other name |
Coagulation factor XIII
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Monthly administration of recombinant factor XIII as preventative treatment of bleeding episodes. Dose: 35 IU/kg body weight intravenous (into the vein).
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Baseline characteristics reporting groups
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Reporting group title |
rFXIII
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Reporting group description |
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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End points reporting groups
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Reporting group title |
rFXIII
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Reporting group description |
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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End point title |
Rate (Number Per Subject Year) of Bleeding Episodes Requiring Treatment With a FXIII Containing Product During the Treatment Period [1] | ||||||||
End point description |
The rate (Number Per Subject Year) of bleeding episodes represents the incidence of bleeding episodes requiring treatment with a FXIII-containing product.
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End point type |
Primary
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End point 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).
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The low bleeding incidence and frequency for patients currently on regular replacement therapy (on average approximately 0.3 bleeds/year) and the low number of patients diagnosed with congenital FXIII deficiency (400-700 patients worldwide) did not allow a statistical comparison of clinical outcome parameters (bleeding events) between rFXIII and any other type of regular replacement therapy with sufficient statistical power. |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events (AEs) were collected and reported during the entire study period i.e. approximately one year (322 days)
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Adverse event reporting additional description |
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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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
13.0
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Reporting groups
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Reporting group title |
rFXIII
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Reporting group description |
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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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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27 Jun 2008 |
The FXIII genotyping will not be made again for those patients if it can be confirmed that the they have Congenital A-subunit deficiency and provided that the results can be made available to NN at screening or prior to administration of trial product. The text in the protocol and Subject Information / Informed Consent were updated accordingly. Regarding the participating countries the protocol will be updated according to the result for the country feasibility. The safety information in the protocol and SI/IC has been updated to include data from recently finalised trial F13CARD-1660. The remaining changes are editorial. |
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12 Dec 2008 |
A few subject selection criteria were slightly reworded or modified as described in Section 9.3. Furthermore, lack of efficacy of rFXIII (as judged by the investigator) was added as a withdrawal criterion.
A sensitivity analysis for the primary endpoint excluding centres that contributed with more than 20% of the total number of subjects was specified. |
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27 Jan 2009 |
No major changes were implemented with this amendment, which specifies precautionary measures
related to pregnancy. |
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10 Jun 2009 |
It was specified that if the Novo Nordisk Safety Committee decided to stop treatment of a subject with rFXIII for safety reasons, the subject could continue in the trial for continued blood and urine sampling for safety evaluation. In addition to recording of bleeding episode and adverse event details, sampling for haematology, biochemistry, urinalysis, FXIII laboratory parameters, immunology, coagulation parameters and clot solubility testing was to be performed prior to administration of standard replacement therapy. |
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25 Nov 2009 |
The subject information/informed consent form was slightly modified due to the fact that two additional subjects had developed non-neutralising antibodies after initiation of treatment with rFXIII. |
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02 Dec 2009 |
This amendment enabled further characterisation of anti-FXIII antibodies. Samples from any subjects in whom anti-FXIII antibodies had been observed following dosing with rFXIII were to be further characterised in order to determine the immunoglobulin isotype of the detected anti-rFXIII antibodies. Additionally, cross-reactivity of subject antibody to plasma-derived FXIII was to be assessed. These analyses were exploratory and were to be presented separately. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/22451421 |
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