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

Study Overview
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Brief Summary
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This trial will provide long-term safety, efficacy and tolerability of ACZ885 in CAPS patients that completed the CACZ885D2307 study

Official Title
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An Open-label Extension Study to Assess Efficacy, Safety and Tolerability of Canakinumab and the Efficacy and Safety of Childhood Vaccinations in Patients With Cryopyrin Associated Periodic Syndromes (CAPS)

Conditions
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Cryopyrin-associated Periodic Syndromes, Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, Neonatal Onset Multisystem Inflammatory Disease

Intervention / Treatment
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* Biological: ACZ885


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients who completed the core CACZ885D2307 study (a patient is defined as having completed the core study if they completed the study up to and including the EOS visit with no major protocol deviations in the core). Male and female patients that are ≥ 1 year of age at the time of the roll-over visit. Parent or legal guardian written informed consent must be obtained before any assessment in the extension CACZ885D2307E1 study is performed. Exclusion criteria: Patients for who continued treatment in the CACZ885D2307E1 extension study is not considered appropriate by the treating physician. Patients who discontinued from the core CACZ885D2307 study Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 4 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: canakinumab<br>Patients will receive a standard dose at an equivalent of 2 mg/kg s.c. of canakinumab (ACZ885) every 8 weeks. Possible dose and/or dosing regimen adjustments that can be administered include: 4 mg/kg s.c. (every 4 to 8 weeks) 6 mg/kg s.c. (every 4 to 8 weeks) 8 mg/kg s.c. (every 4 to 8 weeks) | Biological: ACZ885<br> <br> * Other names: Canakinumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants Without Disease Relapse as Determined by the Physician's Global Assessment of Autoinflammatory Disease Activity, Assessment of Skin Disease and Serological Inflammation Markers. | 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. | Week /80, 104, 128, and 152 (A minimum of 6 months and maximum of 24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity of Canakinumab (ACZ885). Number of Participants With Anti-canakinumab Antibodies | Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using BIAcore system, with detection based on surface plasmon resonance technique. | minimum of 6 months and maximum of 24 months | 
| Change From Baseline (Core Study Baseline) in C--Reactive Protein (CRP) and Serum Amyloid A (SAA) Concentrations | CRP and SAA were used as serologic 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. | Week 0, 80, 104, 128 and 152, last assessment | 
| Frequency Counts of Physician's Global Assessment of Autoinflammatory Disease and Skin Disease | Participants 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 | minimum of 6 months and maximum of 24 months | 
| Number of Vaccination Cases With Protective Antibody Levels Following Immunization With Inactivated Vaccines | Participants who received any inactivated vaccines during the study were assessed for their ability to attain protective antibody levels against the vaccine (antigen) post immunization. Participants vaccinations were not assessed for a response if the antibody titre was already sufficient at pre-dose and maintained during the study. | pre-vaccine dose, Day 28 post-vaccine | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cryopyrin-associated periodic syndromes (CAPS), Familial Cold Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), Neonatal Onset Multisystem Inflammatory Disease (NOMID), children, systemic autoinflammatory disease, CIAS-1 gene, NALP-3, NLRP3, ACZ885, canakinumab, human monoclonal anti-human interleukin-1 antibody, autosomal dominant, familial autoinflammatory syndrome, childhood immunizations vaccinations