Anakinra and Kawasaki Disease (KAWAKINRA)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02390596|
Recruitment Status : Recruiting
First Posted : March 17, 2015
Last Update Posted : September 18, 2018
|Condition or disease||Intervention/treatment||Phase|
|Kawasaki Disease Children||Drug: Anakinra||Phase 2|
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
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase IIa Multicenter Trial to Assess the Efficacy, and Safety of Anakinra in Patients With Intravenous Immunoglobulin-resistant Kawasaki Disease|
|Actual Study Start Date :||February 5, 2016|
|Estimated Primary Completion Date :||April 5, 2019|
|Estimated Study Completion Date :||April 5, 2019|
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 Name: Kineret
- Absence of fever [ Time Frame: within the 48 hours after the treatment by anakinra (after the last escalation dose, if any necessary) ]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)
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02390596
|Contact: Isabelle Koné-Paut, MD, PhD||+33 (0)1 45 21 32 firstname.lastname@example.org|
|Le Kremlin-Bicêtre, France, 94275|
|Contact: Isabelle Koné-Paut, MD, PhD +33 (0)1 45 21 32 46 isabelle.kone-Paut@bct.aphp.fr|
|Principal Investigator:||Isabelle Koné-Paut, MD, PhD||AP-HP, Bicêtre Hospital|