Efficacy and Safety of ACZ885 in Patients With the Following Cryopyrin-associated Periodic Syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease - Study Results

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Treatment
Conditions:	Cryopyrin-associated Periodic Syndromes: Familial Cold Autoinflammatory Syndrome Muckle Wells Syndrome Neonatal Onset Multisystem Inflammatory Disease
Intervention:	Drug: Canakinumab (ACZ885)

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
This study included participants previously enrolled in CACZ885A2102 (NCT00487708), CACZ885D2304 (NCT00465985) and ACZ885 naive patients.

Reporting Groups

	Description
Canakinumab (ACZ885)	Subcutaneous injection every 8 weeks based on participant's body weight. Body weight >40 kilogram (kg): 150 milligrams (mg) per injection and body weight <= 40 kg: 2 mg/kg per injection. For participants who did not experience sufficient symptomatic relief, an up-titration to the dose and/or more frequent doses were permitted as per protocol.

Participant Flow: Overall Study

	Canakinumab (ACZ885)
STARTED	166
COMPLETED	151
NOT COMPLETED	15
Adverse Event	3
Withdrawal by Subject	5
Lack of Efficacy	3
Condition no longer requires study drug	1
Lost to Follow-up	2
Protocol Violation	1

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
Canakinumab (ACZ885)	Subcutaneous injection every 8 weeks based on participant's body weight. Body weight >40 kilogram (kg): 150 milligrams (mg) per injection and body weight <= 40 kg: 2 mg/kg per injection. For participants who did not experience sufficient symptomatic relief, an up-titration to the dose and/or more frequent doses were permitted as per protocol.

Baseline Measures

	Canakinumab (ACZ885)
Number of Participants [units: participants]	166
Age, Customized [units: participants]
>= 3 to < 18 years	47
>= 18 to < 41 years	65
>= 41 to < 75 years	52
>= 75 years	2
Gender [units: participants]
Female	97
Male	69
Disease Characteristics [units: participants]
Muckle-Wells Syndrome	103
Familial Cold Autoinflammatory Syndrome	30
Neonatal Onset Multi-System Inflammatory Syndrome	32
Information Missing	1

Outcome Measures

Hide All Outcome Measures

1. Primary:

The Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs), Discontinuation of Study Drug Due to an AE, Infections and Infestations and Injection Site Reactions [ Time Frame: 2 years depending on when the participant enters the study ]

Measure Type	Primary
Measure Title	The Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs), Discontinuation of Study Drug Due to an AE, Infections and Infestations and Injection Site Reactions
Measure Description	The number of participants with Adverse Events and Infections & Infestations are regardless of study drug relationship by primary system organ class preferred term equal and/or greater than 2% in any group. The number of participants with mild injection site reactions= mild reactions observed on at least one occasion but no moderate or severe reactions. The number of participants with moderate injection site reactions= moderate reactions observed on at least one occasion but no severe reactions.
Time Frame	2 years depending on when the participant enters the study
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Population defined as all participants who received at least one dose of study drug.

Reporting Groups

	Description
Canakinumab (ACZ885)	Subcutaneous injection every 8 weeks based on participant's body weight. Body weight >40 kilogram (kg): 150 milligrams (mg) per injection and body weight <= 40 kg: 2 mg/kg per injection. For participants who did not experience sufficient symptomatic relief, an up-titration to the dose and/or more frequent doses were permitted as per protocol.

Measured Values

	Canakinumab (ACZ885)
Number of Participants Analyzed [units: participants]	166
The Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs), Discontinuation of Study Drug Due to an AE, Infections and Infestations and Injection Site Reactions [units: participants]
Adverse Event	150
Death	0
Serious Adverse Event	18
Discontinuation of study drug due to an AE	4
Infections and Infestations	109
Any Injection Site Reactions	13
Mild Injection Site Reactions	11
Moderate Injection Site Reactions	2

No statistical analysis provided for The Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs), Discontinuation of Study Drug Due to an AE, Infections and Infestations and Injection Site Reactions

2. Secondary:

The Percentage of Participants Without Disease Relapse as Determined by the Physician's Global Assessment of Autoinflammatory Disease Activity, Assessment of Skin Disease and Inflammation Markers. [ Time Frame: Every 8 weeks during the course of the trial for at least 6 months with a maximum duration of 2 years ]

Measure Type	Secondary
Measure Title	The Percentage of Participants Without Disease Relapse as Determined by the Physician's Global Assessment of Autoinflammatory Disease Activity, Assessment of Skin Disease and Inflammation Markers.
Measure Description	Disease relapse following complete response is defined as inflammation markers: C-Reactive Protein (CRP) and/or Serum Amyloid A (SAA) result > 30 mg/L AND Physician's Global Assessment of Autoinflammatory Disease Activity > minimal or Physician's Global Assessment >= minimal AND Skin Disease Assessment > minimal. Physician's Global Assessment of Autoinflammatory Disease Activity and Skin Disease Assessment (urticarial skin rash) are completed by the investigator using a 5 point rating scale: absent, minimal, mild, moderate and severe.
Time Frame	Every 8 weeks during the course of the trial for at least 6 months with a maximum duration of 2 years
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Population defined as all participants who had at least one dose of study drug and were included in the Relapse Assessment.

Reporting Groups

	Description
Canakinumab (ACZ885)	Subcutaneous injection every 8 weeks based on participant's body weight. Body weight >40 kilogram (kg): 150 milligrams (mg) per injection and body weight <= 40 kg: 2 mg/kg per injection. For participants who did not experience sufficient symptomatic relief, an up-titration to the dose and/or more frequent doses were permitted as per protocol.

Measured Values

	Canakinumab (ACZ885)
Number of Participants Analyzed [units: participants]	141
The Percentage of Participants Without Disease Relapse as Determined by the Physician's Global Assessment of Autoinflammatory Disease Activity, Assessment of Skin Disease and Inflammation Markers. [units: Percentage of participants]	90.1

No statistical analysis provided for The Percentage of Participants Without Disease Relapse as Determined by the Physician's Global Assessment of Autoinflammatory Disease Activity, Assessment of Skin Disease and Inflammation Markers.

3. Secondary:

Immunogenicity of Canakinumab (ACZ885) [ Time Frame: Every 8 weeks during the course of the trial for at least 6 months with a maximum duration of 2 years ]

Measure Type	Secondary
Measure Title	Immunogenicity of Canakinumab (ACZ885)
Measure Description	The number of participants who tested positive for anti-ACZ885 antibodies using the Biacore Assay at the end of the study.
Time Frame	Every 8 weeks during the course of the trial for at least 6 months with a maximum duration of 2 years
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Population defined as all participants who received at least one dose of study drug and were tested for anti-ACZ885 antibodies at the end of the study.

Reporting Groups

	Description
Canakinumab (ACZ885)	Subcutaneous injection every 8 weeks based on participant's body weight. Body weight >40 kilogram (kg): 150 milligrams (mg) per injection and body weight <= 40 kg: 2 mg/kg per injection. For participants who did not experience sufficient symptomatic relief, an up-titration to the dose and/or more frequent doses were permitted as per protocol.

Measured Values

	Canakinumab (ACZ885)
Number of Participants Analyzed [units: participants]	156
Immunogenicity of Canakinumab (ACZ885) [units: participants]	0

No statistical analysis provided for Immunogenicity of Canakinumab (ACZ885)

4. Secondary:

Pharmacokinetics [ Time Frame: Every 8 weeks during the course of the trial for at least 6 months with a maximum duration of 2 years ]

Measure Type	Secondary
Measure Title	Pharmacokinetics
Measure Description	Mean Clearance from serum in Liter per Day (CLD) in adult participants >=18, pediatric participants <18 with body weight >40 kg and pediatric participants <18 with body weight <=40 kg.
Time Frame	Every 8 weeks during the course of the trial for at least 6 months with a maximum duration of 2 years
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population defined as all participants who received at least 1 dose of study drug. 3 participants were excluded because dosing information was not available at the time of analysis.

Reporting Groups

	Description
Canakinumab (ACZ885)	Subcutaneous injection every 8 weeks based on participant's body weight. Body weight >40 kilogram (kg): 150 milligrams (mg) per injection and body weight <= 40 kg: 2 mg/kg per injection. For participants who did not experience sufficient symptomatic relief, an up-titration to the dose and/or more frequent doses were permitted as per protocol.

Measured Values

	Canakinumab (ACZ885)
Number of Participants Analyzed [units: participants]	163
Pharmacokinetics [units: L/day] Mean ± Standard Deviation
Adult Participants >= 18 years	0.179 ± 0.084
Pediatric Participants <18 years and >40 kg	0.180 ± 0.145
Pediatric Participants <18 years and <= 40 kg	0.083 ± 0.033

No statistical analysis provided for Pharmacokinetics

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

More Information

Hide More Information

Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300

No publications provided by Novartis

Publications automatically indexed to this study:

Kuemmerle-Deschner JB, Hachulla E, Cartwright R, Hawkins PN, Tran TA, Bader-Meunier B, Hoyer J, Gattorno M, Gul A, Smith J, Leslie KS, Jiménez S, Morell-Dubois S, Davis N, Patel N, Widmer A, Preiss R, Lachmann HJ. Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes. Ann Rheum Dis. 2011 Dec;70(12):2095-102. Epub 2011 Aug 21.

Responsible Party:	Novartis
ClinicalTrials.gov Identifier:	NCT00685373 History of Changes
Other Study ID Numbers:	CACZ885D2306
Study First Received:	May 27, 2008
Results First Received:	April 25, 2011
Last Updated:	July 24, 2012
Health Authority:	United States: Food and Drug Administration Germany: Paul-Ehrlich-Institut Spain: Spanish Agency of Medicines France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) United Kingdom: Medicines and Healthcare Products Regulatory Agency Italy: The Italian Medicines Agency Turkey: Ministry of Health India: Drugs Controller General of India