Clinical Trial Results:
Prospective open-label uncontrolled multi-center post-marketing study to assess inhibitory antibody formation in subjects with congenital C1-INH deficiency and acute hereditary angioedema (HAE) attacks treated with Berinert®, a C1-esterase inhibitor
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Summary
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EudraCT number |
2010-024242-30 |
Trial protocol |
PL HU BG |
Global end of trial date |
17 Oct 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Jul 2016
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First version publication date |
03 May 2015
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Other versions |
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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 |
CE1145_4001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01467947 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
CSL Behring GmbH
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Sponsor organisation address |
Emil-von-Behring-Str. 76, Marburg, Germany, 35041
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Public contact |
Clinical Trial Disclosure Manager, CSL Behring, clinicaltrials@cslbehring.com
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Scientific contact |
Clinical Trial Disclosure Manager, CSL Behring, clinicaltrials@cslbehring.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
23 Jan 2015
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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 |
17 Oct 2014
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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 document the formation of inhibitory anti-C1-esterase-inhibitor (anti-C1-INH) antibodies in subjects with hereditary angioedema (HAE) treated with C1 Esterase Inhibitor (Berinert).
The study evaluated the hypothesis that the incidence of inhibitory anti-C1-INH antibodies in subjects with HAE treated with C1 Esterase Inhibitor is less than 20% of the total study population.
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Protection of trial subjects |
This study was carried out in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice guidelines, and standard operating procedures for clinical research and development at CSL Behring (CSLB). The study protocol and all amendments were approved by the Independent Ethics Committee(s) (IECs) /
Institutional Review Board(s) (IRBs) of the participating centers. Prior to entering the study, subjects were informed, in an understandable form, about the nature, scope, and possible consequences of the study. The investigator was responsible for obtaining a subject’s written informed consent to participate in the study.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 Nov 2011
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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 |
Romania: 15
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Country: Number of subjects enrolled |
Bulgaria: 10
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Country: Number of subjects enrolled |
Hungary: 8
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Country: Number of subjects enrolled |
Poland: 13
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Worldwide total number of subjects |
46
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EEA total number of subjects |
46
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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) |
0
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Adolescents (12-17 years) |
2
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Adults (18-64 years) |
42
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||
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Pre-assignment
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Screening details |
60 subjects were screened and enrolled in the study. 14 subjects did not experience an HAE attack before the study ended and so did not receive study treatment. 46 subjects started and completed the active treatment period of the study. | ||||||
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Period 1
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Period 1 title |
Active Treatment Period (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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C1 Esterase Inhibitor | ||||||
Arm description |
Subjects received 20 U C1 Esterase Inhibitor (C1-INH)/kg body weight by slow intravenous infusion for each acute HAE attack requiring treatment during a 9-month period beginning after their first HAE attack while on study. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
C1 Esterase Inhibitor
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Investigational medicinal product code |
CE1145
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Other name |
Berinert®, C1-INH
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Pharmaceutical forms |
Powder for solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
20 U of C1-INH/kg body weight for the treatment of each HAE attack
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Baseline characteristics reporting groups
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Reporting group title |
C1 Esterase Inhibitor
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Reporting group description |
Subjects received 20 U C1 Esterase Inhibitor (C1-INH)/kg body weight by slow intravenous infusion for each acute HAE attack requiring treatment during a 9-month period beginning after their first HAE attack while on study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
C1 Esterase Inhibitor
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Reporting group description |
Subjects received 20 U C1 Esterase Inhibitor (C1-INH)/kg body weight by slow intravenous infusion for each acute HAE attack requiring treatment during a 9-month period beginning after their first HAE attack while on study. | ||
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End point title |
Number of subjects with inhibitory anti-C1-esterase-inhibitor antibodies [1] | ||||||
End point description |
Subjects with no positive baseline result and at least one positive post-baseline result for inhibitory anti-C1-INH antibodies. Anti-C1-INH antibodies were detected using a direct binding enzyme-linked immunosorbent assay (ELISA). Positive samples were mixed with equal volumes of standard human plasma to assess neutralizing capacity by comparing with normal control samples.
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End point type |
Primary
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End point timeframe |
Baseline to approximately 9 months
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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: Statistical analyses cannot be entered when there is just one treatment group. |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of subjects with any (inhibitory or non-inhibitory) anti-C1-esterase-inhibitor antibodies | ||||||||||||||||
End point description |
Subjects with at least one positive result for inhibitory or non-inhibitory anti-C1-INH antibodies. A direct binding enzyme-linked immunosorbent assay was used to detect inhibitory antibodies to C1-esterase inhibitor.
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End point type |
Secondary
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End point timeframe |
Baseline to approximately 9 months
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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 |
Baseline to approximately 9 months
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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 |
16.0
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Reporting groups
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Reporting group title |
C1 Esterase Inhibitor
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Reporting group description |
Subjects received 20 U C1 Esterase Inhibitor (C1-INH)/kg body weight by slow intravenous infusion for each acute HAE attack requiring treatment during a 9-month period beginning after their first HAE attack while on study. | ||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||
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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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19 Mar 2013 |
- Inclusion Criteria changed to: Diagnosis of congenital C1-INH deficiency (HAE type I or II) period and assessed by the investigator to likely require IV Berinert treatment during the study
- Removal of requirement to confirm postmenopausal status with hormone levels
- Pregnancy test required of all female subjects
- At the discretion of the Investigator, the subject will be allowed to go home after onset of symptom relief
- Microscopic sediment analysis to be completed for any abnormal results in Urinalysis
- Typographical corrections, updates and clarifications in the document. |
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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 | |||
