Clinical Trial Results:
An open-label, long-term safety and efficacy study of ACZ885 (anti-interleukin-1β; monoclonal antibody) administered for at least 6 months in patients with the following cryopyrin-associated periodic syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Muckle-Wells Syndrome with overlapping symptoms of Neonatal Onset Multisystem Inflammatory Disease
|
Summary
|
|
EudraCT number |
2007-004367-22 |
Trial protocol |
GB DE FR ES IT BE Outside EU/EEA |
Global end of trial date |
29 Apr 2010
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
13 Jul 2016
|
First version publication date |
12 Aug 2015
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
CACZ885D2306
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT00685373 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Novartis Pharma AG
|
||
Sponsor organisation address |
CH-4002, Basel, Switzerland,
|
||
Public contact |
Clinical Disclosure Office, Novartis Pharma AG, +41 613241111,
|
||
Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, +41 613241111,
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
|
||
EMA paediatric investigation plan number(s) |
EMEA-000060-PIP01-07 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
29 Apr 2010
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
29 Apr 2010
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The objective of study was to assess the long-term safety and tolerability of canakinumab in subjects with the following cryopyrin associated periodic syndromes (CAPS): Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS) or MWS with overlapping symptoms of Neonatal Onset Multisystem Inflammatory Disease (NOMID).
|
||
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. Canakinumab dose was adjusted done during the course of the study as rescue medication. A rescue dose of 300 milligram (mg) subcutaneous (s.c.) (or 4 mg/kilogram (mg/kg) for subjects with a body weight less than or equal to (≤) 40 kg) by Day 8. Non responders by Day 15 were treated again with same dose as rescue medication and continued with maintenance dose of 600 mg s.c. (or 8 mg/kg for subjects ≤ 40 kg) every 8 weeks.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
19 May 2008
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Spain: 5
|
||
Country: Number of subjects enrolled |
United Kingdom: 17
|
||
Country: Number of subjects enrolled |
Belgium: 1
|
||
Country: Number of subjects enrolled |
France: 42
|
||
Country: Number of subjects enrolled |
Germany: 46
|
||
Country: Number of subjects enrolled |
Italy: 14
|
||
Country: Number of subjects enrolled |
United States: 32
|
||
Country: Number of subjects enrolled |
India: 4
|
||
Country: Number of subjects enrolled |
Turkey: 5
|
||
Worldwide total number of subjects |
166
|
||
EEA total number of subjects |
125
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
26
|
||
Adolescents (12-17 years) |
21
|
||
Adults (18-64 years) |
111
|
||
From 65 to 84 years |
7
|
||
85 years and over |
1
|
||
|
|||||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||||
Recruitment details |
The study was conducted at 32 centres in 8 countries. | ||||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||||
Screening details |
A total of 166 subjects were enrolled into the study. | ||||||||||||||||||||
|
Period 1
|
|||||||||||||||||||||
Period 1 title |
Overall study (overall period)
|
||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||
|
Arm title
|
Canakinumab | ||||||||||||||||||||
Arm description |
Subjects received body-weight stratified dosage of canakinumab (2 mg/kg for subjects ≤ 40 kg or 150 mg for subjects more than (>) 40 kg) s.c. injection every 8 weeks. The dose was escalated to 4 mg/kg or 300 mg respectively at Day 8 if dose of canakinumab was not sufficient to achieve complete response by Day 15, as per investigator's discretion. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Canakinumab
|
||||||||||||||||||||
Investigational medicinal product code |
ACZ885
|
||||||||||||||||||||
Other name |
|||||||||||||||||||||
Pharmaceutical forms |
Powder for solution for injection
|
||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
||||||||||||||||||||
Dosage and administration details |
Canakinumab s.c. injection (2 mg/kg or 150 mg) was administered every 8 weeks.
|
||||||||||||||||||||
|
|||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Canakinumab
|
||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received body-weight stratified dosage of canakinumab (2 mg/kg for subjects ≤ 40 kg or 150 mg for subjects more than (>) 40 kg) s.c. injection every 8 weeks. The dose was escalated to 4 mg/kg or 300 mg respectively at Day 8 if dose of canakinumab was not sufficient to achieve complete response by Day 15, as per investigator's discretion. | ||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Canakinumab
|
||
Reporting group description |
Subjects received body-weight stratified dosage of canakinumab (2 mg/kg for subjects ≤ 40 kg or 150 mg for subjects more than (>) 40 kg) s.c. injection every 8 weeks. The dose was escalated to 4 mg/kg or 300 mg respectively at Day 8 if dose of canakinumab was not sufficient to achieve complete response by Day 15, as per investigator's discretion. | ||
|
|||||||||||||||||||||
End point title |
Number of subjects with adverse events (AEs) and serious adverse events (SAEs), discontinuation of study drug due to an AE, infections and infestations and injection site reactions [1] | ||||||||||||||||||||
End point description |
Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign, 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 hospitalisation, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. Discontinuation was defined as subjects with adverse events that lead to discontinuation of study drug. All infection relevant events were considered as infection by discretion of investigator. Injection site reaction involved pain, redness, swelling, induration, hemorrhage and itching. The analysis was performed in the safety set population defined as defined as subjects who received at least one dose of study drug.
|
||||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||||
End point timeframe |
Day 1 up to Day 729
|
||||||||||||||||||||
| 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. |
|||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||
End point title |
Percentage of subjects without disease relapse | ||||||||
End point description |
Relapse was defined as a Physician’s Global Assessment of autoinflammatory disease activity score more minimal and either C reactive protein (CRP) and either Serum amyloid A (SAA) equal to or more than 30 mg/L, or Physician’s Global Assessment of autoinflammatory disease activity as score more than or equal to minimal and Physician’s global assessment of skin disease score as minimal Physician’s global assessment. Subjects were assessed based on Physician’s Global Assessment on 5-point scale for autoinflammatory disease activity as: 0 = None/absent; 1 = Minimal; 2 = Mild; 3 = Moderate; 4 = Severe.The analysis was performed in the safety set population.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Day 1 to Day 729
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||
End point title |
Number of subjects who required canakinumab additional dose or dose frequency adjustment as assessed by investigator | ||||||||||||
End point description |
The number of subjects who required a dose adjustment of canakinumab or an administration frequency adjustment were defined as subjects who were not complete responders on Day 15 and treated with adjusted dose (canakinumab 300 mg or 4 mg/kg for subjects with less than 40 kg weight), continued with subsequent adjusted dose (canakinumab 600 mg or 8 mg/kg for subjects with less than 40 kg weight). Maintenance of response over time was determined by the Physician’s global assessment of autoinflammatory disease activity, assessment of skin disease and CRP and/or SAA. The analysis was performed in the safety set population.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Day 1 to Day 729
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||
End point title |
Number of subjects with anti-canakinumab antibodies | ||||||
End point description |
Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using Biacore system. The analysis was performed in the safety set population.
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
Day 1 to Day 729
|
||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||||||||
End point title |
Clearance from serum of canakinumab | ||||||||||||||
End point description |
Clearance (CL) was defined as the total body clearance of canakinumab following an extravascular dose from the serum when the systemic bioavailability was unknown.The analysis was performed in the safety set population. The 'n' signifies those subjects evaluable for this measure at specified time points for each group, respectively.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Day 1, Day 8, Day 29, Day 57, Day 113, Day 169, Day 225, Day 281, Day 337, Day 393, Day 449, Day 505, Day 561, Day 617, Day 673 and Day 729
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
13.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Canakinumab
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received body-weight stratified dosage of canakinumab (2 mg/kg for subjects ≤ 40 kg or 150 mg for subjects more than (>) 40 kg) s.c. injection every 8 weeks. The dose was escalated to 4 mg/kg or 300 mg respectively at Day 8 if dose of canakinumab was not sufficient to achieve complete response by Day 15, as per investigator's discretion. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
14 Feb 2008 |
Subjects with severe renal insufficiency (Glomerular Filtration Rate (GFR) < 30 millilitre/minute/1.73 square metre) or planned liver transplantation would not undergo administration of a gadolinium contrast agent for the performance of a magnetic resonance imaging (MRI) evaluation. |
||
20 Feb 2009 |
The age-range of subjects was lowered (3 years or younger), so as to allow for the inclusion of subjects with Neonatal Onset Multisystem Inflammatory Disease (canakinumab naive), and to update the sample size in the protocol. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
