Comparing Anakinra and IVIG for Kawasaki Disease Treatment

A Randomized Phase III Multicenter Trial Comparing the Efficacy and Safety of Anakinra Versus Intravenous Immunoglobulin (IVIG) Retreatment, in Patients With Kawasaki Disease Who Failed to Respond to Initial Standard IVIG Treatment

This study is testing if Anakinra can help children with Kawasaki Disease who didn't get better with the usual IVIG treatment by reducing fever and improving their health within two days.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 84 (estimated)
• Ages: 3 Months to 17 Years
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (other)
• Drugs / interventions: cyclophosphamide
• Locations: 1 site (Le Kremlin-Bicêtre, Val De Marne)
• Trial ID: NCT04656184 on ClinicalTrials.gov

What this trial studies

This trial evaluates the effectiveness and safety of Anakinra, an interleukin-1 receptor antagonist, compared to a second infusion of intravenous immunoglobulin (IVIG) in children with Kawasaki Disease who did not respond to initial IVIG treatment. It is a multicentric, randomized, controlled trial designed to assess whether Anakinra can reduce fever and improve other clinical outcomes within two days of treatment. The study will measure various secondary endpoints, including disease activity, coronary lesions, and inflammation markers. The trial aims to provide insights into alternative treatment options for this serious condition.

Who should consider this trial

Good fit: Ideal candidates are children aged 3 months to under 18 years with Kawasaki Disease who have not responded to initial IVIG treatment.

Not a fit: Patients who have not been diagnosed with Kawasaki Disease or those who have not received initial IVIG treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could offer a new treatment option for children with Kawasaki Disease who do not respond to standard IVIG therapy.

How similar studies have performed: While there have been studies on Kawasaki Disease treatments, the specific comparison of Anakinra to IVIG retreatment is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* Children, male and female, from 3 months to \<18 years old
* Patient ≥ 5 kg
* 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 American Heart Association 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.
* 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 IV Ig. 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

Exclusion Criteria:

* Preterm and neonates, pregnancy, pregnancy and breast feeding
* Suspicion of another diagnosis
* Patient with overt concomitant bacterial, viral or fungal infection
* Patient previously treated with steroids and/or another biotherapy
* Patient with increased risk of tuberculosis infection
* Recent tuberculosis infection or with active tuberculosis
* 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), as long as the patient receives the study medication
* 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 (Tumor Necrosis Factor)), plasmapheresis)
* Hypersensitivity to anakinra or excipients (citric acid, sodium chloride, disodium EDTA (Ethylene Diamine Tetra Acetic), 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 (IgA: Immunoglobulin A)
* 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 the Summary of Products Characteristics (SmPC) of Kineret® and Privigen®
* 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

Where this trial is running

Le Kremlin-Bicêtre, Val De Marne

• CHU de Bicêtre — Le Kremlin-Bicêtre, Val De Marne, France (RECRUITING)

Study contacts

• Study coordinator: Isabelle Koné-Paut, Pr

Conditions: Kawasaki Disease