Clinical Trial: Anakinra and Kawasaki Disease

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase IIa Multicenter Trial to Assess the Efficacy, and Safety of Anakinra in Patients With Intravenous Immunoglobulin-resistant Kawasaki Disease

Brief 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 Summary:

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 2-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
    Sponsor: Assistance Publique - Hôpitaux de Paris

    Current Primary Outcome: Absence of fever [ Time Frame: within the 48 hours after the treatment by anakinra (after the last escalation dose, if any necessary) at d15 at latest ]

    The main efficacy evaluation criterion: the patient must reach a body (axillary, tympanic, oral) temperature <38 within 48 hours of treatment by anakinra (after the last escalation dose, if any necessary) at d15 at latest


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Reduction in physician assessment of disease activity, on a 10 points scale, of at least to 50% [ Time Frame: between baseline and day15 ]
    • Reduction in patient's parents assessment of disease activity, on a 10 points scale, of to at least 50% [ Time Frame: between baseline and day15 ]
    • Resolution of coronary abnormalities by echocardiogram if present [ Time Frame: at day45 ]
    • CRP normalization [ Time Frame: between baseline and day15 ]
    • Adverse events frequency [ Time Frame: between baseline and day45 ]
      Defined with physical exam, injection tolerability, vital signs, TB risk, laboratory evaluations, echocardiogram


    Original Secondary Outcome: Same as current

    Information By: Assistance Publique - Hôpitaux de Paris

    Dates:
    Date Received: March 11, 2015
    Date Started: March 2015
    Date Completion: June 2017
    Last Updated: December 8, 2015
    Last Verified: December 2015