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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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01576367
First received: February 17, 2012
Last updated: June 22, 2016
Last verified: June 2016
  Purpose
This trial will provide long-term safety, efficacy and tolerability of ACZ885 in CAPS patients that completed the CACZ885D2307 study

Condition Intervention Phase
Cryopyrin-associated Periodic Syndromes
Familial Cold Autoinflammatory Syndrome
Muckle-Wells Syndrome
Neonatal Onset Multisystem Inflammatory Disease
Biological: ACZ885
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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. [ Time Frame: Week /80, 104, 128, and 152 (A minimum of 6 months and maximum of 24 months) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Immunogenicity of Canakinumab (ACZ885). Number of Participants With Anti-canakinumab Antibodies [ Time Frame: minimum of 6 months and maximum of 24 months ] [ Designated as safety issue: Yes ]
    Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using BIAcore system, with detection based on surface plasmon resonance technique.

  • Change From Baseline (Core Study Baseline) in C--Reactive Protein (CRP) and Serum Amyloid A (SAA) Concentrations [ Time Frame: Week 0, 80, 104, 128 and 152, last assessment ] [ Designated as safety issue: Yes ]
    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.

  • Frequency Counts of Physician's Global Assessment of Autoinflammatory Disease and Skin Disease [ Time Frame: minimum of 6 months and maximum of 24 months ] [ Designated as safety issue: No ]
    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

  • Number of Vaccination Cases With Protective Antibody Levels Following Immunization With Inactivated Vaccines [ Time Frame: pre-vaccine dose, Day 28 post-vaccine ] [ Designated as safety issue: No ]
    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.


Enrollment: 17
Study Start Date: January 2012
Study Completion Date: October 2015
Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Canakinumab

  Eligibility

Ages Eligible for Study:   1 Year to 4 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01576367

Locations
Belgium
Novartis Investigative Site
Bruxelles, Belgium, 1200
Novartis Investigative Site
Laeken, Belgium, 1020
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 1X8
France
Novartis Investigative Site
Le Kremlin Bicetre, France, 94275
Germany
Novartis Investigative Site
Berlin, Germany, 13353
Novartis Investigative Site
Dresden, Germany, 01307
Novartis Investigative Site
St. Augustin, Germany, 53757
Novartis Investigative Site
Tübingen, Germany, 72076
Spain
Novartis Investigative Site
Granada, Andalucia, Spain, 18012
Novartis Investigative Site
Valencia, Comunidad Valenciana, Spain, 46026
Switzerland
Novartis Investigative Site
Lausanne, Switzerland, 1011
United Kingdom
Novartis Investigative Site
London, United Kingdom, WC1N 1EH
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01576367     History of Changes
Other Study ID Numbers: CACZ885D2307E1  2011-005154-57 
Study First Received: February 17, 2012
Results First Received: June 22, 2016
Last Updated: June 22, 2016
Health Authority: United States: Food and Drug Administration
Germany: Paul Ehrlich Institute
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
Belgium: Belgian Health Care Knowledge Center
Canada: Health Canada
Israel: Ministry of Health

Keywords provided by Novartis:
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

Additional relevant MeSH terms:
Syndrome
Cellulitis
Eosinophilia
Cryopyrin-Associated Periodic Syndromes
Disease
Pathologic Processes
Skin Diseases, Infectious
Infection
Suppuration
Connective Tissue Diseases
Inflammation
Leukocyte Disorders
Hematologic Diseases
Hereditary Autoinflammatory Diseases
Genetic Diseases, Inborn
Skin Diseases, Genetic
Skin Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 09, 2016