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:
NCT01302860
First received: February 22, 2011
Last updated: July 22, 2015
Last verified: July 2015
  Purpose

This trial will assess the safety, efficacy and tolerability of ACZ885 in patients aged 4 years and younger with cryopyrin associated periodic syndromes (CAPS)


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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A One-year Open-label, Multicenter Trial to Assess Efficacy, Safety and Tolerability of Canakinumab (ACZ885) and the Efficacy and Safety of Childhood Vaccinations in Patients Aged 4 Years or Younger With Cryopyrin Associated Periodic Syndromes (CAPS)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentage of Participants Aged 4 Years or Younger With at Least One Complete Response at Week 56 [ Time Frame: Week 56 ] [ Designated as safety issue: No ]
    Complete response was defined as clinical remission and serological remission. Clinical remission was defined as Physician global assessment of auto-inflammatory disease activity as absent or minimal (using a 5-point scale ranging from absent to severe) and assessment of skin disease as absent or minimal (using a 5-point scale ranging from absent to severe). Serological remission was defined as C reactive protein (CRP) or Serum amyloid A protein (SAA) to be less than (<) 15 milligram per liter (mg/L) and <10 mg/L respectively.


Secondary Outcome Measures:
  • Percentage of Participants Aged 2 Years or Younger With at Least One Complete Response at Week 56 [ Time Frame: Week 56 ] [ Designated as safety issue: No ]
    Complete response was defined as clinical remission and serological remission. Clinical remission was defined as Physician global assessment of auto-inflammatory disease activity as absent or minimal (using a 5-point scale ranging from absent to severe) and assessment of skin disease as absent or minimal (using a 5-point scale ranging from absent to severe). Serological remission was defined as CRP or SAA to be <15 mg/L and <10 mg/L respectively.

  • Percentage of Participants With Defined Grades in Physician's Global Assessment Score at Week 56 [ Time Frame: Week 56 ] [ 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.

  • Percentage of Participants With Defined Grades in Physician Assessment of Skin Disease at Week 56 [ Time Frame: Week 56 ] [ Designated as safety issue: No ]
    Participants were assessed by physician for skin disease (urticarial skin rash) measured on a 5--point scale as: 0 = None/absent; 1 = Minimal; 2 = Mild; 3 = Moderate; 4 = Severe.

  • Change From Baseline in C--Reactive Protein (CRP) and Serum Amyloid A (SAA) Concentrations at Week 56 [ Time Frame: Baseline, Week 56 ] [ Designated as safety issue: No ]
    The CRP and SAA were used as 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.

  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 (start of study treatment) up to Week 56 (end of study) ] [ Designated as safety issue: Yes ]
    Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.

  • Percentage of Participants Receiving a Concomitant Vaccination During the Study [ Time Frame: Day 1 (start of study treatment) to Week 56 (end of study) ] [ Designated as safety issue: No ]
    Participants received any one of the following inactivated vaccines as per the immunization program: Corynebacterium diphtheria, Bordetella pertussis, Neisseria meningitidis, Clostridium tetani, Influenza type A, Influenza type B, Haemophilus influenza B, Streptococcus pneumoniae, or Hepatitis B were determined.

  • Number of Vaccination Cases With Protective Antibody Levels Following Immunization With Inactivated Vaccines [ Time Frame: Day -14 (prior-vaccination), Day 0 (vaccination), Day 28, Day 57 (post-vaccination) ] [ 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.

  • Number of Participants With Anti-canakinumab Antibodies at Week 56 [ Time Frame: Week 56 (End of study) ] [ 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.


Enrollment: 17
Study Start Date: November 2010
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Canakinumab
Canakinumab s.c. injection (2 mg/kg) was administered every 8 weeks.
Drug: ACZ885

  Eligibility

Ages Eligible for Study:   1 Month to 60 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female patients that are 28 days up to 60 months of age at the time of the screening visit.
  2. Body weight > or = 2.5 kg.
  3. Parent or legal guardian's written informed consent is required before any assessment is performed for patients.
  4. At study entry, patients should have a clinical diagnosis of FCAS, MWS, or NOMID and symptoms requiring pharmacological intervention. Prior agreement between the Investigator and Novartis for study eligibility is required for patients who do not have a molecular diagnosis of NALP3 mutations available (either testing not performed, or testing performed but negative) upon study entry. For those patients who have not been molecularly tested for NALP3 mutations, molecular testing should be performed during the course of the study.
  5. For patients treated with an IL-1 blocking agent (i.e. anakinra, rilonacept), these treatments should be discontinued prior to the baseline visit and patients must demonstrate active disease prior to treatment.
  6. Patients who are scheduled to receive an immunization, according to their local vaccination guidelines, with an inactivated vaccine must be willing to participate in the assessment schedule for vaccinated patients.

Exclusion Criteria:

  1. Preterm neonates for whom, in the Investigator's judgment, participation in the study is not deemed appropriate.
  2. History of recurrent and/or evidence of active bacterial, fungal, or viral infections (including HIV).
  3. Patients with immunodeficiency or treatment with immunosuppressive drugs.
  4. Live vaccinations within < or = 3 months prior to screening. No live vaccinations will be allowed throughout the course of this study and up to 3 months following the last dose.
  5. Patients with an increased risk of tuberculosis (TB) infection according to following risk factors:

    • Patients with recent close contact with persons known to have active pulmonary TB disease
    • Foreign-born patients from countries with a high prevalence of tuberculosis
    • Patients with recent tuberculosis infection (including children > 6 months with a positive PPD test [defined as an induration of at least 10mm])
    • Patients with end-stage renal disease
    • Patients with diabetes mellitus
    • Patients receiving immunosuppressive therapy
    • Patients with hematologic cancers.
  6. Participation in another trial within the last 30 days or 5 half-lives of the investigational compound (whichever is longer).
  7. Familial and social conditions rendering regular medical assessment not possible.
  8. Pediatric patients with neutropenia (absolute neutrophil count [ANC] < 1.5 x 10 to the 9th/l)

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: NCT01302860

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

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01302860     History of Changes
Other Study ID Numbers: CACZ885D2307, 2009-016859-22
Study First Received: February 22, 2011
Results First Received: July 22, 2015
Last Updated: July 22, 2015
Health Authority: 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
Belgium: Belgian Health Care Knowledge Center
Canada: Health Canada
Switzerland: Swissmedic
United States: Food and Drug Administration

Keywords provided by Novartis:
Cryopyrin-associated periodic syndromes (CAPS)
Familial Cold Autoinflammatory Syndrome (FCAS)
Muckle-Wells Syndrome (MWS) or Neonatal Onset Multisystem Inflammatory Disease (NOMID)
children
systemic autoinflammatory disease
CIAS-1 gene
NALP-3
NLRP3
ACZ885
Ilaris
human monoclonal anti-human interleukin-1 beta (IL-beta)
antibody
autosomal dominant
familial autoinflammatory syndrome

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

ClinicalTrials.gov processed this record on September 03, 2015