Anakinra and Kawasaki Disease

NCT02390596 | Completed Phase 2 DMC

• 2 other identifiers: AOM135202014-002715-41
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Kawasaki Disease; Children

Keywords

Kawasaki disease; anti Interleukin 1 treatment; anakinra; resistance to IVIg; coronary aneurysms; phase II trial

Outcome Measures

Primary Outcomes (1)

• Absence of fever

  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)

  within the 48 hours after the treatment by anakinra (after the last escalation dose, if any necessary)

Secondary Outcomes (5)

• Reduction in physician assessment of disease activity, on a 10 points scale, of at least to 50%

  between baseline and day15

• Reduction in patient's parents assessment of disease activity, on a 10 points scale, of to at least 50%

  between baseline and day15

• Resolution of coronary abnormalities by echocardiogram if present

  at day45

• CRP normalization

  between baseline and day15

• Adverse events frequency

  between baseline and day45

Study Arms (1)

Anakinra

EXPERIMENTAL

Drug: Anakinra

Interventions

Anakinra DRUG

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.

Also known as: Kineret

Anakinra

Eligibility Criteria

• Age: 3 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients, male and female, at any age ≥ 3 months (5 kg) of life, with KD according to the American Heart Association definition for complete or incomplete KD. fever ≥ 5 days and ≥ 4 of 5 main clinical signs: modification of the extremities, polymorphic exanthema, bilateral bulbar not exudative conjunctivitis, erythema of the lips or oral cavity, and cervical lymph nodes usually unilateral \> 1.5 cm in diameter. In the presence of less than 4 clinical criteria and 5 days of fever, the diagnosis of disease KD is proposed in case of coronary abnormalities (at least one dilated coronary artery with internal diameter ≥ 2,5 SD from the mean normalized for body surface area (Z score) as determined by echocardiography. For indicative purpose, in case of incomplete KD, other biological supportive criteria for incomplete KD can help to ensure the diagnosis: leucocytosis, elevated CRP, elevated ESR, anaemia, hyponatremia, elevated ASAT, ALAT and gGT, hyperlipidaemia.
• Patients who failed to respond to standard therapy of KD:, e.g. Persistence or recrudescence of fever ≥ 38°C, 48 hours after the infusion of 2g/kg of IV Ig,
• Weight ≥5Kg
• Patient, parent or legal guardian's written informed consent is required
• Patient with health insurance
• Patient agrees to have effective contraception for the duration of participation in the research

You may not qualify if:

• Preterm and neonates, pregnancy
• Patients suspected with another diagnosis
• Patients with overt concomitant bacterial infection
• Patients previously treated with another biotherapy
• Patients with any type of immunodeficiency or cancer
• Patients with increased risk of TB infection
• Recent tuberculosis infection or with active TB
• Close contact with a patient with TB
• Patients recently arrived less than 3 months from a country with high prevalence of TB
• A chest radiograph suggestive of TB
• Patients with end stage renal disease: NKF stages ≥4; eGFR≤29mL/min/1.73 m2 or diabetes mellitus or neutropenia \<1500/mm3 or liver failure
• Hypersensitivity to the active substance or to any of the excipients (citric acid and anhydrous; sodium chloride disodium edetate dehydrate polysorbate 80; sodium hydroxide; water for injections)
• Patient already included in a biomedical research other than observational (e.g.; cohort, registry)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Swedish Orphan Biovitrum: collaborator

Study Sites (1)

AP-HP,Bicêtre Hospital

Le Kremlin-Bicêtre, 94275, France

Location

Related Publications (1)

• Kone-Paut I, Tellier S, Belot A, Brochard K, Guitton C, Marie I, Meinzer U, Cherqaoui B, Galeotti C, Boukhedouni N, Agostini H, Arditi M, Lambert V, Piedvache C. Phase II Open Label Study of Anakinra in Intravenous Immunoglobulin-Resistant Kawasaki Disease. Arthritis Rheumatol. 2021 Jan;73(1):151-161. doi: 10.1002/art.41481. Epub 2020 Nov 17.

  PMID: 32779863 DERIVED

MeSH Terms

Conditions

Mucocutaneous Lymph Node Syndrome; Coronary Aneurysm

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Vasculitis; Vascular Diseases; Cardiovascular Diseases; Lymphatic Diseases; Hemic and Lymphatic Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Aneurysm

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Isabelle Koné-Paut, MD, PhD

  AP-HP, Bicêtre Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2015
• First Posted: March 17, 2015
• Study Start: February 5, 2016
• Primary Completion: January 21, 2019
• Study Completion: February 18, 2019
• Last Updated: July 2, 2019

Record last verified: 2018-09

Locations

FR (1)