Clinical Trial Results:
Open-label, phase II, single arm study to evaluate the safety, immunogenicity, pharmacokinetics and efficacy of recombinant human C1 inhibitor for the treatment of acute attacks in pediatric patients with hereditary angioedema, from 2 up to and including 13 years of age
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Summary
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EudraCT number |
2011-000987-92 |
Trial protocol |
DE IT CZ SK HU |
Global end of trial date |
17 Jul 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Mar 2018
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First version publication date |
08 Mar 2018
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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 |
C1 1209
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01359969 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Pharming Technologies BV
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Sponsor organisation address |
Darwinweg 24, Leiden, Netherlands, 2333 CR
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Public contact |
Anurag Relan, MD, Pharming Technologies B.V., +31 715247400, a.relan@pharming.com
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Scientific contact |
Anurag Relan, MD, Pharming Technologies B.V., +31 715247400, a.relan@pharming.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-000367-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? |
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 Jul 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
17 Jul 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Jul 2017
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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 assess the clinical safety, immunogenicity and tolerability of Ruconest in the treatment of acute angioedema attacks in 2-13 year old HAE patients.
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Protection of trial subjects |
All study-related procedures were to be hosted in a familiar environment in facilities selected for childcare: the staff were to be trained in communicating to and looking after (young) children and their legal representatives. All study-related procedures (e.g. blood samplings) were to be optimized and modeled in order to minimize risk and distress. Age appropriate information was to be given to the child and his/her representatives prior to any investigations or procedures. Eventual changes in the procedures were to be announced to them well in advance.
For blood sampling it was recommended, for the sake of patient's comfort, to use butterfly needles and to place a catheter during the time of hospitalization for easy blood collection. Also, applying a topical anesthetic before catheter placement was to be considered.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Jan 2012
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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: 1
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Country: Number of subjects enrolled |
Israel: 9
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Country: Number of subjects enrolled |
Romania: 2
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Country: Number of subjects enrolled |
Macedonia, the former Yugoslav Republic of: 2
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Country: Number of subjects enrolled |
Poland: 2
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Country: Number of subjects enrolled |
Czech Republic: 2
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Country: Number of subjects enrolled |
Germany: 1
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Country: Number of subjects enrolled |
Hungary: 1
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Worldwide total number of subjects |
20
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EEA total number of subjects |
8
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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) |
17
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Adolescents (12-17 years) |
3
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Adults (18-64 years) |
0
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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 |
Male and female patients, from 2 up to and including 13 years of age with a clinically suspected and/or confirmed diagnosis of HAE will be recruited for this study. Patients will be identified and invited to participate by the investigators at the respective study centers. | ||||||
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Pre-assignment
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Screening details |
Pts with a med hist of HAE (age 2-13 yrs) were invited for a screening visit. At screening the diagnosis HAE was confirmed via Central lab testing. If the diagnosis was confirmed, pts were eligible for treatment if an acute attack would occur and they presented to study center within 5 hrs of onset of attack. Total: 63 scr, 57 eligible, 20 treated | ||||||
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Period 1
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Period 1 title |
Overall trial (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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Treatment of HAE attack | ||||||
Arm description |
- | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Recombinant human C1 inhibitor
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Investigational medicinal product code |
rhC1INH
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Other name |
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Pharmaceutical forms |
Powder for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
50 U/kg body weight (with a maximum of 4200 U)
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
Out of the 57 eligible subjects, 20 developed one or more treatments during the recruitment period and were treated. The number of treatments varied due to the number of HAE attacks occurring during this period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Intention to treat analysis set
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The set of patients who received at least one dose of the study medication, and for whom any efficacy data is available.
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End points reporting groups
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Reporting group title |
Treatment of HAE attack
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Reporting group description |
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Subject analysis set title |
Intention to treat analysis set
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The set of patients who received at least one dose of the study medication, and for whom any efficacy data is available.
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End point title |
Time to beginning of relief [1] | ||||||||
End point description |
Time to beginning of relief for all attacks is presented.
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End point type |
Primary
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End point timeframe |
Time to beginning of relief of symptoms that showed the response to treatment based on the overall VAS score decrease of ≥ 20 mm from baseline.
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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: As this was an open-label single arm study, no statistical analyses could be provided. The pre defined endpoint was to show relief of symptoms, which was defined as a reduction of ≥ 20 mm on VAS compared the baseline VAS score. In the result section the median time to beginning of relief in minutes is presented with the 95% CI. No comparison has been against a control or placebo group, so therefore no statistical analyses could be presented. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to minimal symptoms | ||||||||
End point description |
Time to minimal symptoms for all attacks is presented.
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End point type |
Secondary
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End point timeframe |
Time to minimal symptoms was defined as the time at which the Overall VAS score fell below 20 mm for all locations where VAS Scores were recorded.
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Adverse events information
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Timeframe for reporting adverse events |
AEs were collected for eligible patients (n=57), commencing with the signing of the ICF through the last follow-up visit, regardless if treatment was given.
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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 |
20.0
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Reporting groups
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Reporting group title |
All treated patients
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Reporting group description |
The reported values are based on the treatment-emergent adverse events (TEAE), which are the AEs with an onset at any time between the start of treatment and 97 days after treatment for any treated attack. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 3% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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25 Aug 2011 |
This amendment was implemented in order to ensure consistent evaluation of the VAS and TEQ efficacy parameters, as it was agreed with the FDA for a concurrent study. Furthermore, in order to obtain consistent immungenicity safety data, anti-rabbit IgE antibody testing is added to the immunology test-panel at Day 28. Also, following remarks from Ethics Committees and Competent Authorities, various corrections are implemented. |
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27 Oct 2011 |
This amendment corrects the investigator's score to reflect the more refined analysis of attack locations. It also specifies the analysis of anti-rabbit epithelium IgE, which assessment was added previously. |
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09 Nov 2012 |
This amendment updates the section about sponsor personnel and stipulates that pregnancies have to be reported as SAE; this has been added to the safety section. Also, some (minor) textual corrections have been made. |
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10 Jun 2014 |
The amendment describes administrative changes. The Pharming Project Manager has been changes as well as the Pharmacovigilance contact details. |
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15 Aug 2014 |
This amendment is prepared upon request of the Czech Republic Competent Authorities (SUKL) and includes country specific updates in the sections of blood sampling procedures to ensure compliance with the guidelines, extension of the reasons for withdrawal and the usage of contraception is removed because sexual intercourse at persons until the age of 15 is illegal in the Czech Republic. |
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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 | |||
