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

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)

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

Study Overview

• Status: Completed
• Conditions: Familial Cold Autoinflammatory Syndrome; Muckle-Wells Syndrome; Neonatal Onset Multisystem Inflammatory Disease; Cryopyrin-associated Periodic Syndromes
• Intervention / Treatment: Biological: ACZ885

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Laeken, Belgium, 1020
    • Novartis Investigative Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Novartis Investigative Site
• France
  • Le Kremlin Bicetre, France, 94275
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Saint Augustin, Germany, 53757
    • Novartis Investigative Site
  • Tübingen, Germany, 72076
    • Novartis Investigative Site
• Spain
  • Andalucia
    • Granada, Andalucia, Spain, 18012
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46026
      • Novartis Investigative Site
• Switzerland
  • Lausanne, Switzerland, 1011
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, WC1N 1EH
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 4 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. 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).
2. Male and female patients that are ≥ 1 year of age at the time of the roll-over visit.
3. Parent or legal guardian written informed consent must be obtained before any assessment in the extension CACZ885D2307E1 study is performed.

Exclusion criteria:

1. Patients for who continued treatment in the CACZ885D2307E1 extension study is not considered appropriate by the treating physician.
2. Patients who discontinued from the core CACZ885D2307 study

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: canakinumab; 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; Other Names: Canakinumab

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Brogan PA, Hofer M, Kuemmerle-Deschner JB, Kone-Paut I, Roesler J, Kallinich T, Horneff G, Calvo Penades I, Sevilla-Perez B, Goffin L, Lauwerys BR, Lachmann HJ, Uziel Y, Wei X, Laxer RM. Rapid and Sustained Long-Term Efficacy and Safety of Canakinumab in Patients With Cryopyrin-Associated Periodic Syndrome Ages Five Years and Younger. Arthritis Rheumatol. 2019 Nov;71(11):1955-1963. doi: 10.1002/art.41004. Epub 2019 Sep 9.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 16, 2012
• Primary Completion (ACTUAL): October 13, 2015
• Study Completion (ACTUAL): October 13, 2015

Study Registration Dates

• First Submitted: February 17, 2012
• First Submitted That Met QC Criteria: April 10, 2012
• First Posted (ESTIMATE): April 12, 2012

Study Record Updates

• Last Update Posted (ACTUAL): September 11, 2018
• Last Update Submitted That Met QC Criteria: August 13, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: ACZ885; canakinumab; Familial Cold Autoinflammatory Syndrome (FCAS); Muckle-Wells Syndrome (MWS); NLRP3; autosomal dominant; NALP-3; familial autoinflammatory syndrome; Cryopyrin-associated periodic syndromes (CAPS); CIAS-1 gene; Neonatal Onset Multisystem Inflammatory Disease (NOMID); children, systemic autoinflammatory disease; human monoclonal anti-human interleukin-1 antibody; childhood immunizations vaccinations
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Infections; Inflammation; Disease; Hematologic Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Hereditary Autoinflammatory Diseases; Skin Diseases, Genetic; Skin Diseases, Infectious; Leukocyte Disorders; Suppuration; Syndrome; Cellulitis; Eosinophilia; Cryopyrin-Associated Periodic Syndromes
• Other Study ID Numbers: CACZ885D2307E1; 2011-005154-57 (EUDRACT_NUMBER)