The objective of this study is:1. To evaluate the efficacy, safety and the tolerance of Canakinumab in 'IVIG-resistent' patients (cohort 1) and 'IVIG-naive' patients (cohort 2) with Kawasaki disease.2. To evaluate the incidence…
ID
Source
Brief title
Condition
- Coronary artery disorders
- Aneurysms and artery dissections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Determine how many patients will be fever-free after administration of
Canakinumab, in which fever-free is defined as a body temperature of <37.5
degrees Celsius after 48 hours.
Secondary outcome
1. Determine how many patients develop coronary artery aneurysms in week 6-8
and at 6 and 12 months after administration of the therapy.
2. The location, number of coronary artery aneurysms (CAA) and diameter.
3. Follow the development of CAA over time with echocardiography.
Background summary
Kawasaki disease (KD) is an IL-1 driven, acute febrile illness and systemic
vasculitis predominantly affecting children younger than 5 years old. The
disease clinically presents as acute systemic inflammation characterized by
fever and bilateral non-exudative conjunctivitis, erythema of the lips and oral
mucosa, edema of palms and soles often with sheet-like desquamation, rash, and
cervical lymphadenopathy. Coronary arteries are especially susceptible to
inflammatory cell infiltration and structural damage which results in coronary
artery aneurysms (CAA) in about 15-25% of untreated KD (Kato, 1996).
These CAA*s -depending on the luminal diameter- have the tendency to continue
to exist and can lead to severe damage in time. Patients who had KD in
childhood have an increased risk for myocardial infarction, arrhythmias and
sudden death during adolescence and early adulthood. This increased risk is
caused by coronary artery damage due to the formation of thrombosis in such an
aneurysm and the long term effects of the inflammation such as plaque and
arterial thickening which can cause obstruction of the normal blood flow.
The first choice of therapy for children with KD is a single infusion with
intravenous immunoglobulins (IVIG); sometimes followed by a second
administration of IVIG in the case of persistent fever. Whenever this second
infusion with IVIG does not give the desired effect, immunomodulators can be
chosen to treat KD patients resistant to IVIG (high dose corticosteroids,
infliximab, methotrexate or cyclophosphamide).
In this research the drug Canakinumab is being researched. Canakinumab is an
anti-human interleukin-1β (IL-1β) antibody and is registered by the Dutch
government for the treatment of a.o. systemic juvenile idiopathic arthritis
(sJIA), however Canakinumab is not registered as a treatment for KD, for this
research is necessary.
Canakinumab has already shown to be effective in treating pediatric and adult
patients with inherited auto-inflammatory conditions presumably derived from
overproduction of IL-1-beta. We assume that overproduction of IL-1β is a key
factor in KD. By inhibition of IL-1β we would combat the inflammatory response.
With this research we want to investigate whether Canakinumab can also combat
the acute symptoms of KD.
Study objective
The objective of this study is:
1. To evaluate the efficacy, safety and the tolerance of Canakinumab in
'IVIG-resistent' patients (cohort 1) and 'IVIG-naive' patients (cohort 2) with
Kawasaki disease.
2. To evaluate the incidence of coronary aneurysms after administration of
Canakinumab
Study design
Open label, monocenter, prospective intervention study
Intervention
Canakinumab will be administered once intraveneously (6 mg/kg)
Study burden and risks
The risk for side effects due to Canakinumab and the inconveniences of the
procedures of the investigation (E9).
Meibergdreef 9
Amsterdam 1105
NL
Meibergdreef 9
Amsterdam 1105
NL
Listed location countries
Age
Inclusion criteria
Written informed consent, must be obtained by the legal guardian(s)
Female / male patients < 12 years
Active Kawasaki disease defined as:
1. fever >= 38.5°C for 4 days
2. four out of five of the following clinical crtiteria: (i) conjuctival
infection, (ii) oral muscous membrane changes, (e.g. infected pharynx or
strawberry tongue), (iii) erythema of hands or feet, (iv)polymorphous rash, (v)
cervical lymphadenopathy
OR
IVIG-nonresponsiveness, defined as persistent fever 48 hours after IVIG
Exclusion criteria
a. Fever for 8 days or longer for IVIG-naive patients (cohort 2)
b. Treatment with biologicals (e.g. Anakinra, Etanercept, Infliximab,
Tocilizumab, Adalimumab)
c. Every other study medication given 30 days prior to inclusion
d. Immunosuppressive drugs given within 3 months prior to inclusion
e. Known history of allergy to biologicals
f. Significant abnormalities on ECG, or symptoms compatible with myocaridal
ischemia or infarction
which may jeopardize the participation to this study.
g. Every other decision of the prjnciple investigator regarding safety or
otherwise that will preclude
inclusion.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-002783-27-NL |
| CCMO | NL68717.018.19 |