Clinical Trial Results:
A one-year open-label, multicenter trial to assess efficacy, safety and tolerability of canakinumab (ACZ885) and the efficacy and safety of childhood vaccinations in patients aged 4 years or younger with Cryopyrin Associated Periodic Syndromes (CAPS)
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Summary
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EudraCT number |
2009-016859-22 |
Trial protocol |
FR DE ES GB BE Outside EU/EEA IE |
Global end of trial date |
19 Nov 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 |
08 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 |
CACZ885D2307
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01302860 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
CH-4002, Basel, Switzerland,
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, +41 613241111,
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, +41 613241111,
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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-000060-PIP01-07 | ||
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 |
19 Nov 2014
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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 |
19 Nov 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 |
The main objective of the study was to assess the efficacy of canakinumab with respect to the treatment response in subjects aged 4 years and younger.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed. Subjects who did not achieve a complete response following canakinumab subcutaneous (s.c.) injection, or who experienced a relapse before the next planned administration, were eligible for a dose up-titration as rescue medication.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Nov 2010
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
24 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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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: 3
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Country: Number of subjects enrolled |
Belgium: 3
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Country: Number of subjects enrolled |
France: 1
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Country: Number of subjects enrolled |
Germany: 5
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
Switzerland: 2
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Worldwide total number of subjects |
17
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EEA total number of subjects |
14
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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) |
6
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Children (2-11 years) |
11
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Adolescents (12-17 years) |
0
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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 |
The study was conducted at 14 centres in 7 countries. | ||||||
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Pre-assignment
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Screening details |
A total of 17 subjects were enrolled into the study. | ||||||
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Period 1
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Period 1 title |
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 |
This was an open-label, single-treatment arm study. Hence, blinding was not applicable.
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Arms
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Arm title
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Canakinumab | ||||||
Arm description |
Subjects received body weight stratified dose of canakinumab 2 mg/kg s.c. injection every 8 weeks. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Canakinumab
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Investigational medicinal product code |
ACZ885
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Other name |
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Canakinumab s.c. injection (2 mg/kg) was administered every 8 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Canakinumab
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Reporting group description |
Subjects received body weight stratified dose of canakinumab 2 mg/kg s.c. injection every 8 weeks. | |||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Canakinumab
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Reporting group description |
Subjects received body weight stratified dose of canakinumab 2 mg/kg s.c. injection every 8 weeks. | ||
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End point title |
Percentage of subjects aged 4 years or younger with at least one complete response at Week 56 [1] | ||||||||
End point description |
Complete response was defined as clinical remission and serological remission. Clinical remission was defined as Physician global assessment of auto-inflammatory disease activity as absent or minimal (using a 5-point scale ranging from absent to severe) and assessment of skin disease as absent or minimal (using a 5-point scale ranging from absent to severe). Serological remission was defined as C reactive protein (CRP) or Serum amyloid A protein (SAA) to be less than (<) 15 milligram per litre (mg/L) and <10 mg/L respectively. The analysis was performed in Full analysis set (FAS), defined as all subjects who received at least one dose of study drug under this study protocol.
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End point type |
Primary
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End point timeframe |
Week 56
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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: Only descriptive summary statistics was planned for this primary outcome measure. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of subjects aged 2 years or younger with at least one complete response at Week 56 | ||||||||
End point description |
Complete response was defined as clinical remission and serological remission. Clinical remission was defined as Physician global assessment of autoinflammatory disease activity as absent or minimal (using a 5-point scale ranging from absent to severe) and assessment of skin disease as absent or minimal (using a 5-point scale ranging from absent to severe). Serological remission was defined as CRP or SAA to be <15 mg/L and <10 mg/L respectively. The analysis was performed in FAS population.
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End point type |
Secondary
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End point timeframe |
Week 56
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| Notes [2] - Subjects aged 2 years or younger |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of subjects assessed for auto inflammatory disease activity by using physician’s global assessment score at Week 56 | ||||||||||||||||||
End point description |
Subjects were assessed based by physician on Physician's Global Assessment measured on a 5-point scale for auto inflammatory disease activity as: 0 = None/absent; 1 = Minimal; 2 = Mild; 3 = Moderate; 4 = Severe. The analysis was performed in FAS population. "Number of Subject analyzed" is the total number of patients with non-missing assessment at the time point.
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End point type |
Secondary
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End point timeframe |
Week 56
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Percentage of subjects with assessment of skin disease by using physician’s global assessment score at Week 56 | ||||||||||||||||||
End point description |
Subjects were assessed by physician for skin disease (urticarial skin rash) on a 5-point scale as: 0 = None/absent; 1 = Minimal; 2 = Mild; 3 = Moderate; 4 = Severe. The analysis was performed in FAS population. "Number of Subject analyzed" is the total number of patients with non-missing assessment at the time point.
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End point type |
Secondary
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End point timeframe |
Week 56
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change from baseline in C-Reactive Protein (CRP) and Serum Amyloid A (SAA) concentrations at Week 56 | ||||||||||||
End point description |
The CRP and SAA were used as inflammatory markers. The target level concentrations for CRP and SAA was ≤15 mg/L and ≤10 mg/L, respectively. Negative change in concentration of inflammatory markers indicated improvement. The analysis was performed in FAS population. Here ‘n’ signifies those subjects with evaluable measurements at both baseline and the post-baseline visit.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 56
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of subjects with adverse events (AEs) and serious adverse events (SAEs) | ||||||||||||||||
End point description |
Adverse events (AEs) were defined as any unfavourable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalisation, cause persistent or significant disability/incapacity, result in ongenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. The analysis was performed in the safety set population defined as subjects who received at least one dose of study drug. Here, ‘n’ signifies subjects evaluable for this measure at specified time points for each group, respectively.
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End point type |
Secondary
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End point timeframe |
Day 1 (start of study treatment) up to Week 56 (end of study)
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Percentage of subjects receiving a concomitant vaccination during the study | ||||||||
End point description |
Subjects receiving any one of the following inactivated vaccines as per the immunization program: Corynebacterium diphtheria, Bordetella pertussis, Neisseria meningitidis, Clostridium tetani, Influenza type A, Influenza type B, Haemophilus influenza B, Streptococcus pneumoniae, or Hepatitis B were determined. The analysis was performed in the FAS population.
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End point type |
Secondary
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End point timeframe |
Day 1 (start of study treatment) to Week 56 (end of study)
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of vaccination cases with protective antibody levels following immunization with inactivated vaccines | ||||||||||||
End point description |
Subjects who received any inactivated vaccines during the study were assessed for their ability to attain protective antibody levels against the vaccine (antigen) post immunization. Subject vaccinations were not assessed for a response if the antibody titre was already sufficient at pre-dose and maintained during the study. The analysis was performed in the FAS population. The data reported in the table based on antibody levels are reporting number of vaccination cases in the respective categories.
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End point type |
Secondary
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End point timeframe |
Day -14 (prior-vaccination), Day 0 (vaccination), Day 28, Day 57 (post-vaccination)
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| Notes [3] - Evaluable subjects who had total 31 vaccinations during study. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of subjects with anti-canakinumab antibodies at Week 56 | ||||||||
End point description |
Immunogenicity assessment included determination of anticanakinumab (ACZ885) antibodies in serum samples using BIAcore system, with detection based on surface plasmon resonance tehnique. The analysis was performed in the safety set population. Here, ‘Number of subjects analysed’ signifies subjects who had immunogenicity samples taken and analyzed during the study.
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End point type |
Secondary
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End point timeframe |
Week 56 (end of study)
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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 |
Serious Adverse Events are monitored from date of First Subject First Visit (FSFV) until Last Subject Last Visit (LSLV). All other adverse events are monitored from First Subject First Treatment until Last Subject Last Visit.
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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 |
17.1
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Reporting groups
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Reporting group title |
Canakinumab
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Reporting group description |
Subjects received body weight stratified dose of canakinumab 2 mg/kg s.c. injection every 8 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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07 Oct 2010 |
1. Dose rationale for the dosing regimen for the study was outlined
2. Exclusion criteria related to live vaccinations was corrected
3. Paediatric subjects with neutropenia were excluded from receiving canakinumab treatment
4. Periodic assessment of neutrophil counts was introduced to monitor and detect neutropenia in subjects while receiving canakinumab treatment
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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 | |||
