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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

Primary Purpose

Cryopyrin-associated Periodic Syndromes, Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ACZ885
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cryopyrin-associated Periodic Syndromes focused on measuring 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

Eligibility Criteria

1 Year - 4 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

canakinumab

Arm Description

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)

Outcomes

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.
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
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
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
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
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.

Full Information

First Posted
February 17, 2012
Last Updated
August 13, 2018
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01576367
Brief Title
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
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)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
January 16, 2012 (Actual)
Primary Completion Date
October 13, 2015 (Actual)
Study Completion Date
October 13, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cryopyrin-associated Periodic Syndromes, Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, Neonatal Onset Multisystem Inflammatory Disease
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Allocation
Non-Randomized
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
canakinumab
Arm Type
Experimental
Arm Description
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)
Intervention Type
Biological
Intervention Name(s)
ACZ885
Other Intervention Name(s)
Canakinumab
Primary Outcome Measure Information:
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 Serological Inflammation Markers.
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
Week /80, 104, 128, and 152 (A minimum of 6 months and maximum of 24 months)
Secondary Outcome Measure Information:
Title
Immunogenicity of Canakinumab (ACZ885). Number of Participants With Anti-canakinumab Antibodies
Description
Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using BIAcore system, with detection based on surface plasmon resonance technique.
Time Frame
minimum of 6 months and maximum of 24 months
Title
Change From Baseline (Core Study Baseline) in C--Reactive Protein (CRP) and Serum Amyloid A (SAA) Concentrations
Description
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.
Time Frame
Week 0, 80, 104, 128 and 152, last assessment
Title
Frequency Counts of Physician's Global Assessment of Autoinflammatory Disease and Skin Disease
Description
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
Time Frame
minimum of 6 months and maximum of 24 months
Title
Number of Vaccination Cases With Protective Antibody Levels Following Immunization With Inactivated Vaccines
Description
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.
Time Frame
pre-vaccine dose, Day 28 post-vaccine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
4 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Novartis Investigative Site
City
Laeken
ZIP/Postal Code
1020
Country
Belgium
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Novartis Investigative Site
City
Le Kremlin Bicetre
ZIP/Postal Code
94275
Country
France
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Novartis Investigative Site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Novartis Investigative Site
City
Saint Augustin
ZIP/Postal Code
53757
Country
Germany
Facility Name
Novartis Investigative Site
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Novartis Investigative Site
City
Granada
State/Province
Andalucia
ZIP/Postal Code
18012
Country
Spain
Facility Name
Novartis Investigative Site
City
Valencia
State/Province
Comunidad Valenciana
ZIP/Postal Code
46026
Country
Spain
Facility Name
Novartis Investigative Site
City
Lausanne
ZIP/Postal Code
1011
Country
Switzerland
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
WC1N 1EH
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
31161734
Citation
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.
Results Reference
derived

Learn more about this trial

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

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