Clinical Trial Results:
Open-label extension study of CE1145 (Human pasteurized C1 esterase inhibitor concentrate) in subjects with congenital C1-INH deficiency and acute HAE attacks
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Summary
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EudraCT number |
2005-003139-38 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
26 Feb 2010
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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 |
06 Aug 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_3003
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00292981 | ||
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-Straße 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 |
17 May 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 |
26 Feb 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 document the use of CE1145 in the treatment of all types of HAE attacks.
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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 |
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Actual start date of recruitment |
31 Aug 2005
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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 |
United States: 55
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Country: Number of subjects enrolled |
Canada: 2
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Worldwide total number of subjects |
57
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EEA total number of subjects |
0
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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) |
1
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Adolescents (12-17 years) |
8
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Adults (18-64 years) |
48
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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 |
This was a multicenter, open-label extension study enrolling subjects at 15 sites in North America that had participated in study CE1145_3001. Enrollment occurred between August 2005 and January 2008. | ||||||||||||||||
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Pre-assignment
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Screening details |
Subjects with hereditary angioedema (HAE) who had participated in study CE1145_3001, or who were eligible, but not treated in study CE1145_3001 because they developed a laryngeal edema were eligible to participate in this extension study. | ||||||||||||||||
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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 | ||||||||||||||||
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Arms
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Arm title
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C1 Esterase Inhibitor | ||||||||||||||||
Arm description |
Participants received C1 Esterase Inhibitor (C1-INH) concentrate 20 Units (U)/kg of body weight by slow intravenous infusion for each acute HAE attack. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
C1 esterase inhibitor concentrate
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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 and solvent for solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
20 U/kg body weight administered by slow intravenous infusion for each acute 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 |
Participants received C1 Esterase Inhibitor (C1-INH) concentrate 20 Units (U)/kg of body weight by slow intravenous infusion for each acute HAE attack. | ||||||||||||||||||||||||||||||||||||||||||||||||
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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 |
Participants received C1 Esterase Inhibitor (C1-INH) concentrate 20 Units (U)/kg of body weight by slow intravenous infusion for each acute HAE attack. | ||
Subject analysis set title |
Intention-to-treat populations
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The Intention-to-treat populations include the ITT subject population and the ITT attack population. The ITT subject population includes all subjects admitted to the study who received any portion of the study medication. The ITT attack population includes all attacks in subjects admitted to the study for which any portion of study medication was administered.
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End point title |
Time to Onset of Relief of Symptoms From HAE Attack, per subject [1] | ||||||||
End point description |
Time between start of study medication administration and onset of relief of symptoms from HAE attack, determined by subject self-assessment. Subjects were asked by the investigator if, taking into account all of the symptoms associated with this HAE attack, they were confident that it was starting to improve. The time of onset of relief from attack was defined by the time determined at the first of the two consecutive "yes" responses. The per-subject analysis used the average of the attacks of each subject.
Intention-to-treat (ITT) population included all subjects admitted to the study who received any portion of the study medication.
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End point type |
Primary
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End point timeframe |
Up to 24 hours after start of study treatment
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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: No formal hypotheses were tested for this endpoint. |
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| Notes [2] - ITT subjects |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Onset of Relief of Symptoms From HAE Attack, per attack [3] | ||||||||
End point description |
Time between start of study medication administration and onset of relief of symptoms from HAE attack, determined by subject self-assessment. Subjects were asked by the investigator if, taking into account all of the symptoms associated with this HAE attack, they were confident that it was starting to improve. The time of onset of relief from attack was defined by the time determined at the first of the two consecutive "yes" responses.
The ITT attack population included all attacks in subjects admitted to the study for which any portion of
study medication was administered.
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End point type |
Primary
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End point timeframe |
Up to 24 hours after start of study treatment
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| Notes [3] - 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: No formal hypotheses were tested for this endpoint. |
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| Notes [4] - ITT attack population Number of HAE Attacks Analyzed: 1085 |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Complete Resolution of All HAE Symptoms, per Subject | ||||||||
End point description |
Complete resolution of symptoms was determined by subject self-assessment and documented on a diary card.
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End point type |
Secondary
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End point timeframe |
Up to Day 9 following an attack
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| Notes [5] - ITT subject population |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Complete Resolution of All HAE Symptoms, per Attack | ||||||||
End point description |
Complete resolution of symptoms was determined by subject self-assessment and documented on a diary card.
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End point type |
Secondary
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End point timeframe |
Up to Day 9 following an attack
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| Notes [6] - ITT attack population Number of HAE Attacks Analyzed: 1085 |
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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 |
For each HAE attack, the AE reporting period comprised the time period from the subject’s enrollment (Day 1) until Day 7 to 9. The reporting period for serious adverse events (SAEs) was 12 Weeks from the time of the first HAE attack.
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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 |
C1 Esterase Inhibitor
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Reporting group description |
Participants received C1 Esterase Inhibitor (C1-INH) concentrate 20 Units (U)/kg of body weight by slow intravenous infusion for each acute HAE attack. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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07 Jul 2006 |
The treatment of laryngeal attacks for subjects screened for, but not treated in, study CE1145_3001 was included. When this amendment was implemented, 17 subjects had already been treated in this extension study. |
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19 Mar 2008 |
The duration of the study period was changed from 24 months after enrollment of the last subject or until the approval in the US (whichever occurred first) to 36 months after treatment of the first attack or until product launch (whichever occurred first). The end of the enrollment period was changed from the end of study CE1145_3001 to 2 months after the end of the study CE1145_3001. Screening could take place on the day of the first attack if the subject was informed about the study in detail prior to Day 1. Attacks were to be excluded from the PP population if <75% of the planned amount of study medication was administered (<90% previously). Additional criteria that led to exclusion of attacks from the PP population were defined. The definition of age groups for subgroup analyses was changed from “<18 years and 18 to <65 years” to “3 to <12 years, 12 to <17 years, and 17 to <65 years”. For the subgroup analysis of subjects with/without androgens, androgens were defined as concomitant danazol and/or stanazolol or ongoing oxandrolone. When the amendment was implemented, all 57 subjects had already been treated in this extension study. |
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29 Oct 2008 |
The assessment of additional safety variables (anti-C1-INH antibodies and hematology, biochemistry, and urinalysis parameters) at different time points was included. An additional sample for viral safety at the end of the study was
also included. The study medication storage temperature was changed from a range of +2°C to +8°C (+36°F to +46°F) to +2°C to +25°C (+36°F to +77°F), based on additional stability tests. Additional subgroup analyses of AEs were included (AEs starting within 24 hours or 72 hours of administration of study medication; AEs by the number of previous infusions of the product at onset of the AE; and AEs except those representing symptoms of abdominal HAE attacks). When
the amendment was implemented, all 57 subjects had already been treated in this extension study. |
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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/21195947 http://www.ncbi.nlm.nih.gov/pubmed/21884533 http://www.ncbi.nlm.nih.gov/pubmed/20635155 http://www.ncbi.nlm.nih.gov/pubmed/24661784 http://www.ncbi.nlm.nih.gov/pubmed/23987198 http://www.ncbi.nlm.nih.gov/pubmed/22856636 |
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