Clinical 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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 Associat

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

Detailed Summary:
Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: Percentage of Participants Aged 4 Years or Younger With at Least One Complete Response at Week 56 [ Time Frame: Week 56 ]

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.


Original Primary Outcome: Long-term efficacy of canakinumab with respect to the maintenance of treatment response in CAPS patients who completed the CACZ885D2307 study [ Time Frame: minimum of 6 months and maximum of 24 months ]

Outcome Measure Description:

Response to treatment (maintained) and evidence of improvement will be collected through the Investigator's clinical assessment of autoinflammatory disease activity, clinical consultations and laboratory monitoring.



Current Secondary Outcome:

  • Percentage of Participants Aged 2 Years or Younger With at Least One Complete Response at Week 56 [ Time Frame: Week 56 ]
    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 ]
    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 ]
    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 ]
    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) ]
    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) ]
    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) ]
    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) ]
    Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using BIAcore system, with detection based on surface plasmon resonance technique.


Original Secondary Outcome:

  • Safety and tolerability as assessed by the overall frequency of adverse events and the number of patients completing the extension study in the overall population [ Time Frame: minimum of 6 months and maximum of 24 months ]

    The occurrence of adverse events will be sought by non-directive questioning of the patient at each visit during the study. Adverse events also may be detected when they are volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.

    Safety Issue:

  • The presence of protective antibody levels following immunization with inactivated (killed) vaccines administered during the extension study [ Time Frame: minimum of 6 months and maximum of 24 months ]
    Assessment of protective antibody titers (IgG) against the following antigens are performed: Diphteria, Pertussis, Tetanus, Haemophilus influenzae type b, Influenza, Pneumococcus, Meningococcus, Hepatitis A & Hepatitis B
  • Safety of canakinumab treatment in pediatric patients receiving a concomitant vaccination during the extension study [ Time Frame: minimum of 6 months and maximum of 24 months ]
    The occurrence of adverse events or reactions will be sought by non-directive questioning of the patient at each visit during the study. Adverse events also may be detected when they are volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
  • The number of patients who relapse during the extension study as determined by the Physician's global assessment of autoinflammatory disease activity, assessment of skin disease and inflammation markers [ Time Frame: minimum of 6 months and maximum of 24 months ]
    Relapse will be defined according to the Physician's global assessment of autoinflammatory disease activity, assessment of skin disease and inflammation markers
  • Inflammation marker (C-reactive protein (CRP) or serum amyloid A (SAA)) after treatment initiation [ Time Frame: A minimum of 6 months and maximum of 24 months ]
    C-reactive protein (CRP) and serum amyloid A (SAA) will be measured at pre-specified timepoints during the study and at the time of dose adjustment.


Information By: Novartis

Dates:
Date Received: February 17, 2012
Date Started: January 2012
Date Completion:
Last Updated: February 28, 2017
Last Verified: February 2017