Anakinra and Kawasaki Disease (KAWAKINRA)

July 1, 2019 updated by: Assistance Publique - Hôpitaux de Paris

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Le Kremlin-Bicêtre, France, 94275
        • AP-HP,Bicêtre Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

3 months to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Anakinra
Drug: Anakinra
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.
Other Names:
  • Kineret

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Absence of fever
Time Frame: within the 48 hours after the treatment by anakinra (after the last escalation dose, if any necessary)
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Reduction in physician assessment of disease activity, on a 10 points scale, of at least to 50%
Time Frame: between baseline and day15
between baseline and day15
Reduction in patient's parents assessment of disease activity, on a 10 points scale, of to at least 50%
Time Frame: between baseline and day15
between baseline and day15
Resolution of coronary abnormalities by echocardiogram if present
Time Frame: at day45
at day45
CRP normalization
Time Frame: between baseline and day15
between baseline and day15
Adverse events frequency
Time Frame: between baseline and day45
Defined with physical exam, injection tolerability, vital signs, TB risk, laboratory evaluations, echocardiogram
between baseline and day45

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Swedish Orphan Biovitrum

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Isabelle Koné-Paut, MD, PhD, AP-HP, Bicêtre Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 5, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 21, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 18, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 11, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 11, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 17, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 2, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 1, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AOM13520
  • 2014-002715-41 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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