Anakinra treatment is expected to reduce the early and long-term mortality of patients with Kawasaki Disease (KD), by a rapid and sustained effect on vascular inflammation.
Conditions
Interventions
Trade Name: KINERET 100 mg / 0.67 mL
Product Name: KINERET
Pharmaceutical Form: Solution for infusion in pre-filled syringe
INN or Proposed INN: ANAKINRA
CAS Number: 143090-92-0
Concentration unit: mg
Sponsors
Assistance Publique – Hôpitaux de Paris (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Children, male and female, from 3 months to 1.5 cm in diameter. - Patients who failed to respond to the standard therapy of KD, e.g. Persistence or recrudescence of fever = 38°C, 48 hours after the infusion of 2g/kg of IVIG. Patients may be screened 24h after the end of the first infusion if they remain febrile 24h after the end of the first infusion. - Patient, parents or legal guardian’s written informed consent is required - Patient with health insurance (SS or CMU) Efficient contraception for the duration of participation in the research for childbearing aged women Are the trial subjects under 18? yes Number of subjects for this age range: 84 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Preterm and neonates, pregnancy and breast feeding - Suspicion of another diagnosis - Patient with other concomitant bacterial, viral or fungal infection - Patient previously treated with steroids and/or another biotherapy - Patient with increased risk of TB infection - Recent tuberculosis infection or with active TB - Patient with any type of immunodeficiency or cancer - Patients with severe renal impairment (CLcr < 30 ml/minute) - Patients with hepatic insufficiency - Patients with neutropenia (ANC<1.5 x109/l) - Patients included in another interventional protocol Patient under the following treatments: - Preventive Antipyretics (paracetamol, NSAIDs other than aspirin 30-50mg/kg given for purpose of KD inflammation) - 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) - Hypersensitivity to anakinra or excipients (citric acid, sodium chloride, disodium EDTA, polysorbate 80, sodium hydroxide, in water for injection) - Hypersensitivity to IV Ig, or excipients (L-proline and water for injection), hypersensitivity to human normal immunoglobulin, in particular if the patient have anti-IgA antibodies - Patients with type I or II hyperprolinemia - Live vaccines within 1 month prior to enrollment -Hypersensitivity to anakinra or to immunoglobulins or to excipients of Kineret® or Privigen® or to E.coli proteins - Contraindication for administration of anakinra or IVIG listed in SmPC of Kineret® and Privigen®
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of Anakinra (IL-1R1 receptor antagonist) with 2nd IVIG infusion, in second line, on fever in patients with KD, who failed to respond to one infusion of IVIG(standard treatment). 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 (i.e. a binary outcome: success/failure). ;Secondary Objective: To compare Anakinra with IVIG retreatment in terms of: - Efficacy on fever at 72h - Efficacy on disease activity - Efficacy on KD symptoms - Efficacy on coronary lesions (e.g.: dilatation and aneurysm) - Efficacy on inflammation - Safety and tolerability ;Primary end point(s): 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 (i.e. a binary outcome: success/failure).;Timepoint(s) of evaluation of this end point: 2 days after initiation of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To compare Anakinra with IVIG retreatment in terms of: - Temperature <38°C within 3 days (72h) after initiation of treatment - Decrease of the CRP values from baseline to day 30(CRP<6 mg/L at day 30) - Reduction in physician assessment of disease activity, on a 10 points scale, of at least to 50% between baseline and day 14. - 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. - Resolution of coronary abnormalities; i.e worst Z score <2.5, by echocardiogram if present at day 45. - Adverse events: pain/redness at injection site, bacterial infection hepatitis, macrophage activation syndrome, severe neutropenia, - Monitoring of adverse events o Physical examination: Complete clinical exam will be performed at each visit to detect symptoms of KD (rash, cervical nodes, mucous lesions, extremities, GI, pulmonary, CV, neurologic and muscular/joint evaluation) and possible associated morbidity: e.g. concomitant infection o Local tolerability of injections: will be evaluated by physician from V2 to V8: pain, redness, swelling, induration, itching, haemorrhage, (and quoted from none, mild, moderate, severe) o Vital signs and body measurements: at each visit: V1 to V9. The body temperature will be measured daily until d30. Parents will receive a follow-up booklet.. o Laboratory evaluations: hematologic, hepatic and renal assessment will be followed ;Timepoint(s) of evaluation of this end point: days 3 (72h) after initiation of treatment, day 14, day 30, day 45, Day 60 | — |
Countries
France
Contacts
Public ContactMalika Yahmi
Assistance Publique – Hôpitaux de Paris
Outcome results
None listed