ANAKINRA for Kawasaki disease

Inclusion criteria

• {"criterion_text":"- Children, male and female, from 12 months to <18 years old\n- Patient ≥ 7,5 kg\n- Patient with KD according to the American Heart Association definition for complete or incomplete KD. (Fever ≥ 5 days (or at least 3 days if KD with AHA criteria since the third days of fever) and ≥ 4 of 5 main clinical signs: modification of the extremities, polymorphic exanthema, and bilateral bulbar not exudative conjunctivitis, erythema of the lips or oral cavity, and cervical lymph nodes usually unilateral > 1.5 cm in diameter\n- Patients not responding to standard therapy for KD, i.e, persistence or recrudescence of fever (≥38°C) during the 24 to 48 hours following the end of the IVIG infusion (2g/kg).Patients with fever lasting at least 5 days (≥5 days) and up to 11 days inclusive (≤ 11days).\n- Patient, parents or legal guardian’s written informed consent is required\n- Patient with health insurance (SS or CMU)\n- Efficient contraception for the duration of participation in the research for childbearing aged women"}

Exclusion criteria

• {"criterion_text":"- Preterm and neonates, pregnancy and breast feeding\n- Patients with neutropenia (ANC<1.5 x109/l)\n- Patients included in another interventional protocol* Patient under the following treatments:\n- Immunosuppressive medications given in a period less than twice of their half-life prior the patient receives the study medication (systemic steroids, cyclosporine, tacrolimus, azathioprine, cyclophosphamide, interferon, mycophenolate, other anti-IL-1, anti IL-6, anti CD20 and anti TNF), plasmapheresis)\n- Hypersensitivity to anakinra (Kineret®) or excipients (citric acid, sodium chloride, disodium EDTA, polysorbate 80, sodium hydroxide, in water for injection)\n- Hypersensitivity to IV Ig (Privigen®), or excipients (L-proline and water for injection), hypersensitivity to human normal immunoglobulin, in particular if the patient have anti-IgA antibodies\n- Ongoing or recent use of any other medication Known inhibitors/inducers of cytochrome P450 as listed on the link below: http://medicine.iupui.edu/clinpharm/ddis/main-table\n- Suspicion of another diagnosis\n- Patient with overt concomitant bacterial, viral or fungal infection\n- Patient previously treated with steroids and/or another biotherapy\n- Patient with increased risk of TB infection (e.g. close contact with a patient with tuberculosis, stay in a country with a high prevalence of tuberculosis for at least 3 months)\n- Recent tuberculosis infection or with active TB (e.g abnormal chest X-ray: systematized lung disease, non-systematized lung disease, diffuse infiltrative images, pleural effusion, adenopathy, cardiomegaly).\n- Patient with any type of immunodeficiency or cancer\n- Patients with severe renal impairment (CLcr < 30 ml/minute)\n- Patients with hepatic insufficiency"}

Primary endpoints

• {"endpoint_text":"- The main criterion-evaluating efficacy in both groups is: the patient must reach a body (axillary (+0.5°C), tympanic, oral) temperature <38˚C within 2 days after initiation of treatment (considering time of the last escalation dose if any) (i.e. a binary outcome: success/failure).","definition_or_measurement_approach":"Binary outcome (success/failure): measured body temperature (axillary (+0.5°C), tympanic, oral) <38°C within 2 days after initiation of treatment (considering time of last escalation dose if any)."}

Secondary endpoints

• {"endpoint_text":"- Temperature <38˚C within 3 days (72h) after initiation of treatment","definition_or_measurement_approach":"Measured body temperature <38°C within 72 hours after treatment initiation."}
• {"endpoint_text":"- Decrease of the CRP values from baseline to day 30 (CRP<6 mg/L at day 30)","definition_or_measurement_approach":"Change in C-reactive protein (CRP) from baseline to day 30; target CRP<6 mg/L at day 30."}
• {"endpoint_text":"- Reduction in physician assessment of disease activity, on a 10 points scale, of at least to 50% between baseline and day 14.","definition_or_measurement_approach":"Physician global assessment on a 10-point scale; reduction ≥50% between baseline and day 14."}
• {"endpoint_text":"- Reduction in patient’s parent’s assessment of disease activity, on a 10 points scale, of to at least 50% between baseline and day 14.","definition_or_measurement_approach":"Parent/caregiver assessment on a 10-point scale; reduction ≥50% between baseline and day 14."}
• {"endpoint_text":"- Resolution of coronary abnormalities; i.e worst Z score <2.5, by echocardiogram if present at day 45.","definition_or_measurement_approach":"Echocardiographic assessment of coronary artery Z score; resolution defined as worst Z score <2.5 at day 45 if abnormalities present."}
• {"endpoint_text":"- Adverse events: pain/redness at injection site, bacterial infection, hepatitis, macrophage activation syndrome, severe neutropenia,","definition_or_measurement_approach":"Safety monitoring of specified adverse events (local injection site reactions, infections, hepatitis, macrophage activation syndrome, severe neutropenia) as recorded during follow-up."}

France

Earliest CTIS Part Ii Submission Date

18-10-2024

Latest Decision Or Authorization Date

30-12-2025

Processing Time Days

438

Number Of Sites

11

Number Of Participants

84

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"DGOS (Direction Générale de l'Offre de Soins), Ministry of Health, France","duties_or_roles":"Monetary support / funding","organisation_type":"Government / Ministry of Health"}