Clinical Trial Results:
An Open Label Study to Assess the Safety, Tolerability and Efficacy of Canakinumab (ACZ885) in Patients Aged 4 Years or Older Diagnosed With Cryopyrin-associated Periodic Syndromes (CAPS) in Canada
Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.novfor complete trial results.
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Summary
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EudraCT number |
2015-003491-69 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
17 May 2012
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Jul 2018
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First version publication date |
06 Jul 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 |
CACZ885DCA01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01105507 | ||
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 May 2012
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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 May 2012
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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 evaluate safety and tolerability of canakinumab in Canadian patients with CAPS defined as:
• Familial Cold Autoinflammatory Syndrome (FCAS)/ Familial Cold Urticaria (FCU);
• Muckle-Wells Syndrome (MWS);
• Neonatal-Onset Multisystem Inflammatory Disease (NOMID)/ Chronic Infantile Neurological, Cutaneous, Articular Syndrome (CINCA).
To assess the maintenance of response over time under routine medical care in patients with the following CAPS related diseases: FCAS/FCU, MWS, NOMID/CINCA.
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Protection of trial subjects |
In order to avoid relapse, rescue medication with canakinumab was allowed during the course of the study with the stipulation that once a patient received this medication, telephone contact with the patient was necessary to determine if there was a response to treatment. In addition, investigators advised Novartis of the occurrence of such events so that investigational drug stocks could be replenished.
Some patients may have required rescue medication for a brief period of time. In this case, patients returned to their previous dosing regimen if the reason for rescue medication had subsided, based on the Investigator’s judgment.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Aug 2010
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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 |
Canada: 4
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Worldwide total number of subjects |
4
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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) |
2
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
2
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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 |
- | ||||||||||
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Pre-assignment
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Screening details |
Informed consent was obtained for patient’s > 18 years of age in writing before any assessment was performed. For patients < 18 years of age, the parent or legal guardian provided informed consent and an Assent Form was available for the children when appropriate. Consent was obtained at the Screening/Baseline visit. | ||||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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ACZ885 | ||||||||||
Arm description |
Canakinumab was administered subcutaneously. Individuals whose body weight was > 40 kg received 1 mL of solution for injection at a concentration of 150 mg/mL. For patients with a body weight ≥ 15 kg and ≤ 40 kg, a dose of 2 mg/kg subcutaneous was administered. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
ACZ885
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Investigational medicinal product code |
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Other name |
canakinumab
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Canakinumab for injection in 6 mL glass vials each containing nominally 150 mg study drug as a lyophilized cake. Reconstitution was achieved by addition of 1.0 mL water for injection and canakinumab was administered subcutaneously.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
ACZ885
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Reporting group description |
Canakinumab was administered subcutaneously. Individuals whose body weight was > 40 kg received 1 mL of solution for injection at a concentration of 150 mg/mL. For patients with a body weight ≥ 15 kg and ≤ 40 kg, a dose of 2 mg/kg subcutaneous was administered. | ||
Subject analysis set title |
Subject A
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Health related quality of life evaluation per subject.
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Subject analysis set title |
Subject B
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Health related quality of life evaluation per subject.
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Subject analysis set title |
Subject C
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Health related quality of life evaluation per subject.
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Subject analysis set title |
Subject D
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Health related quality of life evaluation per subject.
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End point title |
The percentage of patients with complete response to treatment at Day 8 [1] | ||||||||
End point description |
Complete response is defined as Investigator’s clinical assessment of disease activity ≤ minimal (using a 5-point scale ranging from absent to severe); assessment of skin disease ≤ minimal (using a 5-point scale ranging from absent to severe) and normal serum values of CRP and/or SAA (< 10 mg/L) .
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End point type |
Primary
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End point timeframe |
Day 8
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analyses have not been reported for this primary end point. |
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| No statistical analyses for this end point | |||||||||
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End point title |
The percentage of complete responders who relapsed after showing a complete response at Day 8 [2] | ||||||||
End point description |
For complete responders, relapse was defined as the following criteria (assessed on the same day): CRP and/or SAA value > 30 mg/L AND Investigator’s clinical assessment of disease activity > minimal or the investigator’s clinical assessment of disease activity ≥ minimal AND assessment of skin disease > minimal.
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End point type |
Primary
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End point timeframe |
Day 169 (Month 6 visit)
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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: Statistical analyses have not been reported for this primary end point. |
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End point title |
Evaluation of health-related quality of life and productivity assessed using the medical outcome short form (36) health survey (SF-36®) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Each patient completed the SF-36 scale (Physical Functioning (PF), Role Physical (RP), Bodily Pain (BP),
General Health (GH) Vitality (VT), Social Functioning(SF), Role Emotional (RE) and Mental Health (MH)) and Physical Component (PCS) and Mental Component (MCS) summary scores was computed and plotted using the norm-based scoring.
The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability.
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End point type |
Secondary
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End point timeframe |
Every 6 months until the end of study (Baseline, Month 6, 12 and 18)
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| Notes [3] - 999.99 = no data reported [4] - 999.99 = no data reported |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Evaluation of health-related quality of life and productivity assessed using the Health Assessment Questionnaire (HAQ©) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Twenty specific activities are assessed on a 4-point Likert scale where 0 = without difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do. The 20 activities are grouped into 8 functional categories with each category given a single score equal to the maximum value of their component activities (0, 1, 2, or 3).
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End point type |
Secondary
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End point timeframe |
Every 6 months until the end of study (Baseline, Month 6, 12 and 18)
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| Notes [5] - 999.99 = no data reported |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Subject's treatment adherence with canakinumab for the duration of the study | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline through week 72
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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 reported in this record are from date of 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 |
15.0
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Reporting groups
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Reporting group title |
Canakinumab
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Reporting group description |
Canakinumab | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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23 Feb 2011 |
The main purpose of this amendment was to clarify information related to rescue medication, concomitant therapy and efficacy and safety assessment sections of the clinical study protocol.
The rescue medication section was updated to provide more clarity regarding alternative dosing for patients experiencing insufficient symptomatic relief.
A correction was required regarding the washout time frame for Anakinra; the protocol was amended to be more in line with washout time frames currently prescribed in other Novartis protocols evaluating similar indications.
The efficacy assessment section was modified in order to reflect study operational changes.
The self-injection and health utilization patient questionnaires were removed from the study protocol as patients were not required to self inject and information initially planned to be collected using the health utilization questionnaire was already being collected via the other patient reported outcomes.
No safety assessments were added to the protocol; however more detailed wording was provided in the safety section to clarify the procedures. The sample size was reduced in line with more realistic estimates; since there was no formal statistical hypothesis the reduction of sample size does not alter the trial objectives or planned analysis. Timelines, typographical errors and minor inconsistencies were corrected. |
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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. | |||
| Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.novfor complete trial results. | |||
