Anakinra and Kawasaki Disease
Condition: Kawasaki Disease; Children
MeSH terms: Mucocutaneous Lymph Node Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      The study is designed to assess the efficacy and safety of anakinra, an interleukin 1
      receptor antagonist, in patients with Kawasaki disease who failed to respond to standard
      treatment:e.g. one infusion of 2g/kg of intravenous immunoglobulins.
    

Detailed description: 
      Kawasaki disease (KD), is the most frequent vasculitis in children before 5 years, and the
      main cause of acquired cardiomyopathy in adulthood. The prognosis of KD is influenced by
      early recognition and treatment by intravenous immunoglobulins (IVIG), which represent the
      standard of care and decrease significantly the risk of coronary aneurysms. Despite a first
      infusion of IVIG, 20% of KD patients remain febrile and are at high risk of coronary
      vasculitis. To date there is no agreement for a more effective second line treatment. On the
      basis of the autoinflammatory pattern of KD, we hypothesize that anti IL-1 blocking agents
      could bring a rapid and sustained effect on systemic and coronary inflammation in patients
      with KD.

      Aim of the study

        -  To assess the efficacy of anakinra (IL-1R1receptor antagonist) in patients with KD who
           fail to respond to one infusion of IVIg (standard treatment).

        -  To assess the efficacy of anakinra on disease activity

        -  To assess the efficacy of anakinra on coronary lesions (eg: dilatation and aneurysm

        -  To assess the safety and tolerability of anakinra Patients and methods A Proof of
           concept (quasi experimental, non randomized cohort) study. This is a 3-year open-label,
           prospective multicenter trial of Anakinra in patients with acute KD who failed to
           respond to a first infusion of IVIG within 48h. Patients will be eligible to enter the
           study if they have persistence (or recrudescence of fever) within 48 hours after the
           infusion of IVIg, and if they have given their informed consent to enter the study.
           After appropriate screening, the study treatment will be initiated between J7 and J14
           days of illness to expect full clinical effect. The only primary endpoint will be the
           absence of fever after 48 h of treatment (assessed at J3 of study treatment, visit 3,
           before the third injection of anakinra). If the patient remains febrile (fever >38°C),
           he will receive a double dose of anakinra (4mg/kg) at day 3 instead of 2mg/kg. Treatment
           will be continued until they have achieved complete response as defined in the outcome
           measurement section, and during a maximum of 15 days.

      Expected results and expected public health benefit Anakinra treatment is expected to reduce
      the early and long term mortality of patients with KD, by a rapid and sustained effect on
      vascular inflammation. The safety of anakinra is expected to be good, as the drug has a very
      short half-life, which allows its rapid withdrawal in case of serious adverse event. The use
      of anakinra, is not associated with the risk of contamination by infectious agents, which
      remains even minimal, a possibility with the use of IVIG
    

Intervention name(s): Anakinra
Intervention type(s): Drug
Intervention description(s): The dose of Anakinra will be 2mg/kg (patients <10kg and/or <8 months: 4mg/kg). If the patient remains febrile (fever >38°C), he will receive a double dose of anakinra 4mg/kg (patients <10kg and/or <8 months: 6mg/kg) at day1 instead of 2mg/kg. If the patient does not respond to the 4mg/kg dose at visit 3; d1 within 24 hours, he will receive at visit 4; d2, 6mg/kg of anakinra (patients <10kg and/or <8 months: 8mg/kg). Treatment will be continued until they have achieved complete response as defined in the outcome measurement section, and during a maximum of 15 days.
Other intervention name(s): Kineret
Intervention MeSH terms: Interleukin 1 Receptor Antagonist Protein
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Kawasaki disease; anti Interleukin 1 treatment; anakinra; resistance to IVIg; coronary aneurysms; phase II trial