Clinical Trial Results:
An open-label, phase II dose titration study of ACZ885 (human anti-IL-1beta monoclonal antibody) to assess the clinical efficacy, safety, pharmacokinetics and pharmacodynamics in patients with NALP3 mutations
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Summary
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EudraCT number |
2004-002980-26 |
Trial protocol |
GB DE ES FR Outside EU/EEA |
Global end of trial date |
17 Jul 2008
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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 |
09 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 |
CACZ885A2102
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00487708 | ||
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) |
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? |
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 Jul 2008
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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 Jul 2008
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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 administered through intravenous (i.v.) infusion and subcutaneous (s.c.) injection in order to improve the clinical status of the subjects with mutations in NALP3 gene.
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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.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
31 Jan 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 |
Spain: 1
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Country: Number of subjects enrolled |
United Kingdom: 8
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Country: Number of subjects enrolled |
France: 2
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Country: Number of subjects enrolled |
Germany: 21
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Country: Number of subjects enrolled |
India: 2
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Worldwide total number of subjects |
34
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EEA total number of subjects |
32
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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) |
4
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Adolescents (12-17 years) |
3
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Adults (18-64 years) |
27
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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 9 centres in 5 countries. | ||||||||||||||
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Pre-assignment
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Screening details |
A total of 34 subjects were enrolled in the 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 | ||||||||||||||
Blinding implementation details |
As the current study was an open label study, this section was not applicable.
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Arms
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Arm title
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Canakinumab | ||||||||||||||
Arm description |
Dosage Stage 1: First dose was a single administration of 10 mg/kg i.v., the 2nd dose was a single administration of 1 mg/kg i.v. upon relapse. On second relapse, single administration of 150 mg s.c. Dosage Stage 2: Repeat single administration of 150 mg s.c. upon each relapse (in children from 4 to 16 years an equivalent of 2 mg/kg s.c.). If needed: rescue dose of 5 or 10 mg/kg i.v. | ||||||||||||||
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 and solvent for solution for injection/infusion
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Routes of administration |
Intravenous use, Subcutaneous use
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Dosage and administration details |
Canakinumab powder for solution [10 mg/kg i.v infusion or 1 mg/kg i.v. infusion or 150 mg s.c. or 2 mg/kg s.c] was administered.
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Baseline characteristics reporting groups
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Reporting group title |
Canakinumab
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Reporting group description |
Dosage Stage 1: First dose was a single administration of 10 mg/kg i.v., the 2nd dose was a single administration of 1 mg/kg i.v. upon relapse. On second relapse, single administration of 150 mg s.c. Dosage Stage 2: Repeat single administration of 150 mg s.c. upon each relapse (in children from 4 to 16 years an equivalent of 2 mg/kg s.c.). If needed: rescue dose of 5 or 10 mg/kg i.v. | |||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Canakinumab
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Reporting group description |
Dosage Stage 1: First dose was a single administration of 10 mg/kg i.v., the 2nd dose was a single administration of 1 mg/kg i.v. upon relapse. On second relapse, single administration of 150 mg s.c. Dosage Stage 2: Repeat single administration of 150 mg s.c. upon each relapse (in children from 4 to 16 years an equivalent of 2 mg/kg s.c.). If needed: rescue dose of 5 or 10 mg/kg i.v. | ||
Subject analysis set title |
Canakinumab 1mg/kg i.v
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects who received single dose of canakinumab 1 mg/kg i.v during the study.
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Subject analysis set title |
Canakinumab 10 mg/kg i.v
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects who received single dose of canakinumab 10 mg/kg i.v during the study.
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Subject analysis set title |
Canakinumab 150mg sc
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects who received single dose of canakinumab 150mg sc during the study.
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Subject analysis set title |
Canakinumab 2mg/kg s.c
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects who received single dose of canakinumab 2mg/kg s.c during the study.
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Subject analysis set title |
Canakinumab rescue i.v
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Subjects who received single dose of canakinumab Rescue i.v during the study.
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End point title |
Time from each dose administration to relapse after achieving a complete response to treatment [1] | ||||||||||||||||||||
End point description |
Complete response to treatment was defined as Physician global assessment of disease activity to be equal or less than(≤) minimal using a 5-point scale(0:absent, 1:minimal, 2: mild, 3:moderate and 4: severe); assessment of skin disease ≤ minimal on a 5-point scale(0: absent to 4:severe) and serum values of C-reactive protein (CRP)and/or serum amyloid A protein(SAA) to be <10 milligrams/litres (mg/L). Relapse was defined as Physician global assessment score of disease activity>minimal or Physician global assessment score to be minimal and assessment of skin disease >minimal; and CRP and/or SAA to be more than 30 mg/L compared to baseline. Subjects were grouped by combined dosing regimen where rescue dose was combined with previous dosing regimen. The analysis was performed in safety analysis set, defined as all subjects who received at least one dose of study medication. The 'n' signifies those subjects evaluable for this measure at specified time points for each group, respectively.
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End point type |
Primary
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End point timeframe |
Day 1 up to Day 29 (all 3 periods averaged)
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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 outcome measure. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Serum concentrations of C-Reactive Protein (CRP) and Serum Amyloid A protein (SAA) [2] | ||||||||||||||||||||||||||||||||||||
End point description |
The C-reactive protein (CRP) and Serum amyloid A protein (SAA) were used as inflammatory markers to diagnose the Muckle Wells Syndrome (MWS). The target serum level concentration of CRP and SAA was equal to or less than 10 milligrams/litres (mg/L). The analysis was performed in safety analysis set population. Here "number of subjects analysed' represents evaluable subjects in each treatment arm.
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End point type |
Primary
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End point timeframe |
End of treatment period (all 3 periods averaged)
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| Notes [2] - 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 outcome measure. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of subjects with defined grades in physician’s global assessment score [3] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Subjects were assessed by physician based on Physician’s Global Assessment on 5-point scale for disease activity as: 0 = absent; 1 = Minimal; 2 = Mild; 3 = Moderate; 4 = Severe. The analysis was performed in safety analysis set population.
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End point type |
Primary
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End point timeframe |
Day 1 up to Day 29
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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: Only descriptive summary statistics was planned for this outcome measure. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Percentage of subjects with clinically significant abnormal audiogram | ||||||||||||||||
End point description |
Audiogram was utilized to monitor bilateral sensorineural deafness in subjects with a clinical picture of Familial Cold Autoinflammatory Syndrome (FCAS). Subjects who presented abnormal audiogram at baseline, were followed-up by the investigator for any clinically significant abnormality in the audiogram assessments. The analysis was performed in safety analysis set population. Here, 'Number of subjects analysed' signifies evaluable subjects for audiogram assessment.
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End point type |
Secondary
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End point timeframe |
Baseline, Month 4, Month 8 and Month 12
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Assessment the subject’s renal function at end of period | ||||||||||||||||
End point description |
Renal function parameters like creatinine clearance values and estimated Glomerular filtration rate (eGFRs) were assessed. The eGFR was estimated from serum creatinine, using either the 4-variable Modification of Diet in Renal Disease (MDRD) formula for adults and adolescent subjects, or the Schwartz formula for pediatrics (aged minimum of 12 years). The analysis was performed in safety analysis set population. The 'n' signifies those 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 |
Baseline (first period), Day 1 (post-dose), Week 5 (post-dose), end of period (all 3 periods averaged)
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Health-related quality of life (HRQoL) scores in adult subjects | ||||||||||||||||||||||||
End point description |
Assessment of HRQoL in adult subjects was based on three types of questionnaire: Health Assessment Questionnaire (HAQ), Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) and Medical Outcome Short Form (SF-36) Health Survey summary scores as reported by subjects. In HAQ, higher score (maximum of 3) indicated a more severe disease. The FACIT-F questionnaire assessed general health status with emphasis on fatigue with maximum score of 52, and a higher score indicated less fatigue. SF-36 was separated into the physical and mental components with scores ranging from 0 to 100, and a higher score indicated a better QoL. The analysis was performed in safety analysis set population. The 'n' signifies those 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 |
Baseline, Day 1 (post-dose), Week 1 (post-dose), Week 5 (post dose), end of treatment period (all 3 periods averaged)
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Health-related quality of life (HRQoL) scores in paediatric subjects | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Health¬ related quality of life was assessed in paediatric subjects by child health questionnaire (CHQ-CH87) which had 14 scales and score ranged from 0 to 100 where a higher score indicated a better quality of health. The analysis was performed in safety analysis set population. The 'n' signifies those 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 |
Baseline, Day 1 (post-dose), Week 1 (post-dose), Week 5 (post dose), end of treatment period (all 3 periods averaged)
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Maximum observed plasma concentration (Cmax) | ||||||||||||
End point description |
Maximum observed serum concentration following drug administration from the raw serum concentration-time data was determined. The analysis was performed in safety analysis set population. Here, 'Number of subjects analysed' in 10 mg/kg i.v arm was related to only Stage 1, adult subjects and 150 mg sc arm was related to both Stage 1 and 2 adult subjects.
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End point type |
Secondary
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End point timeframe |
Day 1 (pre-dose), Day 2, 3, 8, 15, 22, Day 29
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| No statistical analyses for this end point | |||||||||||||
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End point title |
AUC from time zero to extrapolated infinite time [AUC (0 - ∞)] | ||||||||||||
End point description |
Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). AUC(0-infinity) was estimated as AUC 0-t + C t /λ z, where λ z was the terminal elimination rate constant. The analysis was performed in safety analysis set population. Here, 'Number of subjects analysed' in 10 mg/kg i.v arm was related to only Stage 1, adult subjects and 150 mg sc arm was related to both Stage 1 and 2 adult subjects.
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End point type |
Secondary
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End point timeframe |
Day 1 (pre-dose), Day 2, 3, 8, 15, 22, Day 29
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Apparent serum clearance (CL/F) | ||||||||
End point description |
The apparent serum clearance (CL/F) was calculated as Dose/AUC0-∞, where CL was the clearance of the drug and F was the absolute oral bioavailability. The analysis was performed in safety analysis set population. Here, 'Number of subjects analysed; signifies stage 1 and 2 adult subjects in 150 mg sc arm.
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End point type |
Secondary
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End point timeframe |
Day 1 (pre-dose), Day 2, 3, 8, 15, 22, Day 29
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to reach maximum observed plasma concentration (Tmax) | ||||||||||||
End point description |
Time required to reach peak or maximum concentration following drug administration. The analysis was performed in safety analysis set population. Here, 'Number of subjects analysed' in 10 mg/kg i.v arm was related to only Stage 1, adult subjects and 150 mg sc arm was related to both Stage 1 and 2 adult subjects.
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End point type |
Secondary
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End point timeframe |
Day 1 (pre-dose), Day 2, 3, 8, 15, 22, Day 29
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Elimination half-life (T1/2) | ||||||||||||
End point description |
The elimination half-life associated with the terminal slope (lz) of a semi logarithmic concentration-time curve. The analysis was performed in safety analysis set population. Here, 'Number of subjects analysed' in 10 mg/kg i.v arm was related to only Stage 1, adult subjects and 150 mg sc arm was related to both Stage 1 and 2 adult subjects.
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End point type |
Secondary
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End point timeframe |
Day 1 (pre-dose), Day 2, 3, 8, 15, 22, Day 29
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Apparent volume of distribution at steady state (Vss) | ||||||||
End point description |
Volume of distribution at steady state calculated from i.v. data. The analysis was performed in safety analysis set population. Here, 'Number of subjects analysed; signifies stage 1 adult patients in 10 mg/kg i.v arm.
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End point type |
Secondary
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End point timeframe |
Day 1 (pre-dose), Day 2, 3, 8, 15, 22, Day 29
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| No statistical analyses for this end point | |||||||||
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End point title |
Apparent volume of distribution during terminal phase (Vz/F) | ||||||||
End point description |
The apparent volume of distribution during terminal phase was estimated. The analysis was performed in safety analysis set population. Here, 'Number of subjects analysed; signifies stage 1 and 2 adult patients in 150 mg sc arm.
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End point type |
Secondary
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End point timeframe |
Day 1 (pre-dose), Day 2, 3, 8, 15, 22, Day 29
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| No statistical analyses for this end point | |||||||||
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End point title |
Area under the concentration-time curve from time zero to the last measurable concentration sampling time(AUCtlast) | ||||||||||||
End point description |
Area under the concentration-time curve from time zero to the last measurable concentration sampling time (tlast) was estimated. The analysis was performed in safety analysis set population. Here, 'Number of subjects analysed' in 10 mg/kg i.v arm was related to only Stage 1, adult subjects and 150 mg sc arm was related to both Stage 1 and 2 adult subjects.
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End point type |
Secondary
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End point timeframe |
Day 1 (pre-dose), Day 2, 3, 8, 15, 22, Day 29
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Serum concentration of total Interleukin-1β (IL-1β) | ||||||||||||||||||||||||
End point description |
Pharmacodynamics of canakinumab was assessed by total IL-1β (sum of free and bound IL-1β) concentration, determined in serum by means of competitive ELISA assay with limit of detection at 0.1 picogram/millilitre (pg/mL). The analysis was performed in safety analysis set population.
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End point type |
Secondary
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End point timeframe |
Day 1 (pre-dose), Day 2, 3, 8, 15, 22, Day 29
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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 |
An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not related to study drug. A SAE was defined as an event which was fatal or life threatening, required or prolonged hospitalization, was significantly or permanently disabling or incapacitating, constituted a congenital anomaly or a birth defect, or encompassed any other clinically significant event that could jeopardize the subject or require medical or surgical intervention to prevent one of the aforementioned outcomes. The analysis was performed in safety analysis set population. The 'n' signifies those 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 |
From start of study treatment to 4 weeks post dose
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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 any visit | ||||||||||
End point description |
The immunogenicity potential of canakinumab during the study was evaluated by surface plasmon resonance spectroscopy using a validated Biacore binding assay. The analysis was performed in safety analysis set population. The 'n' signifies those 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 |
Pre-dose, Week 4 (post dose), at each relapse before re-treatment, end of study (all 3 periods averaged)
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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 are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient 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 |
11.0
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Reporting groups
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Reporting group title |
Pediatric
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Reporting group description |
Pediatric | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Adult
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Reporting group description |
Adult | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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30 Jun 2005 |
Additional blood samples were added for pharmacogenomics to investigate whether the observed early gene expression changes were transient or whether they were stable throughout the remission period. |
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05 Sep 2005 |
A third treatment period was included in the study design in order to explore the efficacy, safety and tolerability, pharmacokinetic and pharmacodynamic of s.c.administration of canakinumab as compared with i.v administration. |
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21 Dec 2005 |
1. Additional s.c. treatment periods were included in the study design in order to explore the efficacy, safety and tolerability, PK and PD of repeat s.c. administration of canakinumab as compared with i.v. administration.
2. Included up to 14 additional subjects, directly starting with the s.c. dosing regimen, assessment of s.c. administration to reach remission and for how long, and, by applying the experience in the first 4 subjects, whether the 10 mg/kg infusion was to be considered as a loading dose for the induction of remission.
3. Procedures added to introduce an interim analysis, to review preliminary efficacy, safety, tolerability, PK, PD, and pharmacogenomics results related to the i.v. administration. |
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21 Sep 2006 |
1. New centres opened in other countries than the original UK site in order to facilitate subjects access to canakinumab.
2. Increasesd the sample size in Stage 2 to 21 additional subjects, i.e. a total number of up to 25 subjects enrolled in the study.
3. Included children aged ≥ 4 years to provide an effective treatment early in the course of this genetically driven disease.
4. Included preliminary assessment of the potency of canakinumab to modify mid to longterm disease progression with regards to deafness, kidney function, neurological and ophthalmological symptoms.
5. Included preliminary assessment of the efficacy of canakinumab to modify HRQoL.
6. Day 3 visit was removed from Period 2 onwards. |
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05 Mar 2007 |
Baseline and pre-dose blood sampling were revised for safety, efficacy, and pharmacogenomics. |
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26 Apr 2007 |
1. Allowed the enrollment of subjects even though their baseline CRP and SAA were less than 30 mg/L, on a case-by-case basis. The definition of relapse for these subjects was adapted to reflect this change.
2. Subjects with renal transplant and with history/evidence of lymphoma were excluded.
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24 Jul 2007 |
1. Increased the total sample size to up to 50 subjects enrolled in the study in order to facilitate subjects access to canakinumab, based on the increasing demand by the
Investigators to enroll more subjects than a maximum of 25, and to allow enrollment of so far unidentified subjects with high unmet medical need.
2. Allowed the subjects who had previously been treated with canakinumab to be enrolled in the study. |
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04 Feb 2008 |
Ensured that subjects with severe renal insufficiency (GFR < 30 mL/min/1.73 m^2) or planned liver transplantation would not undergo performance of an magnetic resonance imaging evaluation in order to avoid administration of a gadolinium contrast agent, based on new safety information and as requested by German Health Authorities. |
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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 | |||
