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Kawasaki DiseasePhase 2KAWAKINRANCT02390596

Anakinra and Kawasaki Disease

A Phase 2 study testing Anakinra in people with Kawasaki Disease and Children, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 3 months to 18 years
Conditions the study is for
Kawasaki Disease, Children
What is being tested?
Anakinra
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteFrance
Study dates
5 Feb 2016to 18 Feb 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 months to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 13Show fewer
  • 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)

Trial locations and contacts

1 site in 1 country.

France1 site

  • AP-HP,Bicêtre Hospital

    Le Kremlin-Bicêtre, 94275

Other trials in France

About this study

Official title: A Phase IIa Multicenter Trial to Assess the Efficacy, and Safety of Anakinra in Patients With Intravenous Immunoglobulin-resistant Kawasaki Disease

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.

Read the detailed description

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

Being tested
Anakinra
Keywords
Kawasaki disease, anti Interleukin 1 treatment, anakinra, resistance to IVIg, coronary aneurysms, phase II trial
Medical subject headings
Mucocutaneous Lymph Node Syndrome, Coronary Aneurysm

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AnakinraDrug

    Also called Kineret

    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.

Study groups in NCT02390596
Study groupRoleWhat they receive
AnakinraExperimentalNot described
Receives: Drug: Anakinra

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

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

Secondary outcomes (5)

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

    Measured: between baseline and day15

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

    Measured: between baseline and day15

  3. Resolution of coronary abnormalities by echocardiogram if present

    Measured: at day45

  4. CRP normalization

    Measured: between baseline and day15

  5. Adverse events frequency

    Defined with physical exam, injection tolerability, vital signs, TB risk, laboratory evaluations, echocardiogram

    Measured: between baseline and day45

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2015 (estimated)
  2. Study start5 Feb 2016
  3. Primary completion21 Jan 2019
  4. Study completion18 Feb 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02390596
Sponsor's protocol ID
AOM13520
Other IDs
2014-002715-41, 2014
Acronym
KAWAKINRA
Status last verified
Sep 2018
First submitted
11 Mar 2015
Last updated
2 Jul 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 32779863

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anakinra in people with Kawasaki Disease and Children, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Absence of fever (time frame: within the 48 hours after the treatment by anakinra (after the last escalation dose, if any necessary)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02390596, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2019.

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