Kawasaki DiseasePhase 4NIKITANCT06697431
Non Inferiority KawasakI Trial With Anakinra
A Phase 4 study testing Anakinra and Intravenous Immunoglobulins, Human in people with Kawasaki Disease and Anakinra, run by Meyer Children's Hospital IRCCS.
Trial summary
This is a multicenter, open-label, randomized, controlled, interventional trial followed by a long-term observational extension period in patients with Kawasaki Disease (KD) to be treated eitherwith endovenous Immunoglobulins (IVIG-standard treatment) versus anakinra Aim of the study: to demonstrate that anakinra is… Read more about this study
- Who is it for?
- Ages 1 month to 16 years
- Conditions the study is for
- Kawasaki Disease, Anakinra
- What is being tested?
- Anakinra and Intravenous Immunoglobulins, Human
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2025to 1 Apr 2027
- Phase
- Phase 4
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 1 month to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- KD defined in at least one of the three following ways as per American Heart Association (AHA) criteria: Fever for at least 5 days in addition to 4 of the following 5 clinical criteria:
- bilateral non-purulent conjunctivitis
- cervical lymphadenopathy
- polymorphous skin rash
- changes in lips or mucosa (strawberry tongue, red cracked lips, diffuse erythematous oropharynx)
- extremity changes (erythema, oedema of palms and soles in initial phase, and at convalescent stage skin peeling)
Show all 14Show fewer
- less than 5 days of fever but all 5 clinical criteria above
- incomplete KD cases defined as:
- children/adolescents (>1 year old) with fever greater than or equal to 5 days AND at least 2 other compatible clinical criteria as listed above;
- OR infants ≤ 1 year old with fever greater than or equal to 7 days without other explanation;
- AND for both age groups, CRP ≥30 mg/L or erythrocyte sedimentation rate (ESR) ≥40 mm/hr (or both) AND for both age groups EITHER the presence of any 3 or more of: anaemia for age (haemoglobin < lower limit of normal reference range for local laboratory); platelet count ≥450,000/L or <140,000/L; albumin <30 g/L; elevated ALT (> upper limit of normal reference range for local laboratory); white cell count ≥15,000/L; urine ≥10 white blood cells per high power field iv.
- OR abnormal echocardiogram compatible with KD but without established CAA, with ≥ 3 of the following suggestive features: decreased left ventricular function, mitral regurgitation, pericardial effusion, or dilated but non-aneurysmal coronary arteries (internal diameter 2≤Z<2.5; and not meeting the exclusion criteria for aneurysmal change as defined below).
- To be enrolled children need to show persistent fever ≤7 days
- Written informed consent from an appropriate legal representative(s), and assent from patients older than 7 years
Who cannot join
- Patients with KD and already established coronary artery aneurysms (CAA), as per AHA definition, at screening.
- Clinical picture consistent with Kawasaki Shock Syndrome (KDSS) or Macrophage Activation Syndrome (MAS) OR Multisystem Inflammatory Syndrome in Children (MIS-C)
- History or evidence of any previous heart disease
- Known hypersensitivity to anakinra, IVIG and ASA or any medical condition that contraindicates the use of these treatments
- Patients with KD receiving IVIG, corticosteroids, immunosuppressants, biologic treatments at the time of screening
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: A Randomized, Controlled, Open-label, Non Inferiority KawasakI Trial With Anakinra
This is a multicenter, open-label, randomized, controlled, interventional trial followed by a long-term observational extension period in patients with Kawasaki Disease (KD) to be treated eitherwith endovenous Immunoglobulins (IVIG-standard treatment) versus anakinra
Aim of the study: to demonstrate that anakinra is non-inferior to IVIG in KD, in terms of fever control in the acute phase and development of coronary artery dilation/aneurisms (CAA) within one year from the onset.
Read the detailed description
This is a multicenter national, open label, randomized, controlled, interventional trial followed by a long-term observational extension period. This is a non-inferiority study Patients who fulfill the eligibility criteria and whose parent/carer (legal representative) has provided informed consent will be randomized 1:1 to receive either
- IVIG 2g/kg administered in 10-12 hours as per local standard of care (standard treatment) OR
- Anakinra 2mg/kg intravenously, max 100 mg/dose 4 times/day (investigational treatment)
PLUS Aspirin (ASA) 50mg/kg QID until 36 hours from fever disappearance, then switched to low-dose (3-5 mg/Kg once a day) as per standard of care
- Conditions
- Kawasaki Disease, Anakinra
- Being tested
- Anakinra, Intravenous Immunoglobulins, Human
- Medical subject headings
- Mucocutaneous Lymph Node Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnakinraDrug
Also called Kineret
Patients who fulfill the eligibility criteria a will be randomized 1:1 to receive either
- IVIG 2g/kg administered in 10-12 hours as per local standard of care (standard treatment) OR
- Anakinra 2mg/kg intravenously, max 100 mg/dose 4 times/day (investigational treatment)
Patients showing fever, between 36 hours and 72 hours from the end of first line treatment will be considered failures. Failures from the investigational treatment arm will receive a dose of IVIG and they will drop from the study.
Children who remained afebrile between the 36th and 72nd hour will be considered as responders, and they will proceed into the study.
Patients in the standard treatment arm will continue ancillary treatment and follow-up .
Patients in the investigational treatment arm will enter the tapering phase.
Intravenous Immunoglobulins, HumanDrug
Also called IVIG
see previous section
| Study group | Role | What they receive |
|---|---|---|
| Anakinra | Experimental | Anakinra 2mg/kg intravenously, max 100 mg/dose 4 times/day Receives: Drug: Anakinra |
| Intravenous immunoglobulins | Active comparator | IVIG 2g/kg administered in 10-12 hours as per local standard of care Receives: Drug: Intravenous Immunoglobulins, Human |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with treatment response in both treatment arms
Response rate
Measured: 12 months
Number of patients with CAA (as per Z-scores) at the end of the study period in both treatment arms
CAA rate in both arms. CAAs will be classified in accordance with the scheme based on Z scores proposed by AHA. No coronary involvement with Z score <2, dilation only with Z score > 2 to <2.5 or if initially <2 with a decrease during follow-up ≥1 3, small aneurysm with Z score ≥2.5 to <5, medium aneurysm with Z score ≥5 to <10 and absolute dimension <8 mm and large or giant aneurysm with Z score ≥10, or absolute dimension ≥8 mm
Measured: 12 months
Secondary outcomes (8)
Number of days with fever in both treatment arms
Fever as defined as T>38°C
Measured: 90 days
Time to reach CRP values<50% from the highest value and to normalize it in both treatment arms (days)
CRP values expressed in mg/dL
Measured: 90 days
Time to normalize coronary artery abnormalities (days)
CAAs will be classified in accordance with the scheme based on Z scores proposed by AHA. No coronary involvement with Z score <2, dilation only with Z score > 2 to <2.5 or if initially <2 with a decrease during follow-up ≥1 3, small aneurysm with Z score ≥2.5 to <5, medium aneurysm with Z score ≥5 to <10 and absolute dimension <8 mm and large or giant aneurysm with Z score ≥10, or absolute dimension ≥8 mm
Measured: 90 days
Severity of coronary artery abnormalities (as per Z-score) at the end of follow-up
CAAs will be classified in accordance with the scheme based on Z scores proposed by AHA. No coronary involvement with Z score <2, dilation only with Z score > 2 to <2.5 or if initially <2 with a decrease during follow-up ≥1 3, small aneurysm with Z score ≥2.5 to <5, medium aneurysm with Z score ≥5 to <10 and absolute dimension <8 mm and large or giant aneurysm with Z score ≥10, or absolute dimension ≥8 mm
Measured: 24 months
Length of hospitalization in both treatment arms (days)
Defined by days of hospitalization from disease onset to discharge
Measured: 90 days
Time to stop anakinra (days)
From the first administration iv to the last sc
Measured: 90 days
Adverse event and severe adverse event developed during the study and follow/up period
Medical Dictionary for Regulatory Activities (MeDRA) will be used for the description of adverse events (AEs), according to the regulatory requirements
Measured: 24 months
Cumulative drug exposure (mg/kg/day)
Calculated for both iv e sc administration
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2024
- Study start1 Apr 2025 (estimated)
- Primary completion1 Apr 2026 (estimated)
- Study completion1 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Kawasaki DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients who fulfill the eligibility criteria and whose parent/carer (legal representative) have provided informed consent will be randomized 1:1 to receive standard of care IVIG and aspirin or anakinra and ASA. As epidemiological data suggest worse outcomes in terms of CAA for very young patients (age \<1 years), in this setting, proper randomisation 1:1 procedure will be matched for age \< or\> than 1 year
- Masking
- None (open label)
- Enrolment
- 38 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Meyer Children's Hospital IRCCS
- Sponsor type
- University, hospital or other
- Collaborators
- Asst Degli Spedali Civili Di Brescia, IRCCS Burlo Garofolo
- Responsible party
- Principal investigator, Gabriele Simonini, Meyer Children's Hospital IRCCS
- Investigators
- Gabriele Simonini, Prof, Principal investigator, Meyer Children's Hospital IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06697431
- Sponsor's protocol ID
- NIKITA
- Acronym
- NIKITA
- Status last verified
- Nov 2024
- First submitted
- 1 Nov 2024
- Last updated
- 21 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Yang J, Jain S, Capparelli EV, Best BM, Son MB, Baker A, Newburger JW, Franco A, Printz BF, He F, Shimizu C, Hoshino S, Bainto E, Moreno E, Pancheri J, Burns JC, Tremoulet AH. Anakinra Treatment in Patients with Acute Kawasaki Disease with Coronary Artery Aneurysms: A Phase I/IIa Trial. J Pediatr. 2022 Apr;243:173-180.e8. doi: 10.1016/j.jpeds.2021.12.035. Epub 2021 Dec 23.
PubMed 34953816Kone-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 32779863Kessel C, Kone-Paut I, Tellier S, Belot A, Masjosthusmann K, Wittkowski H, Fuehner S, Rossi-Semerano L, Dusser P, Marie I, Boukhedouni N, Agostini H, Piedvache C, Foell D. An Immunological Axis Involving Interleukin 1beta and Leucine-Rich-alpha2-Glycoprotein Reflects Therapeutic Response of Children with Kawasaki Disease: Implications from the KAWAKINRA Trial. J Clin Immunol. 2022 Aug;42(6):1330-1341. doi: 10.1007/s10875-022-01301-w. Epub 2022 Jun 14.
PubMed 35699824Blonz G, Lacroix S, Benbrik N, Warin-Fresse K, Masseau A, Trewick D, Hamidou M, Stephan JL, Neel A. Severe Late-Onset Kawasaki Disease Successfully Treated With Anakinra. J Clin Rheumatol. 2020 Mar;26(2):e42-e43. doi: 10.1097/RHU.0000000000000814. No abstract available.
PubMed 32073531Bossi G, Codazzi AC, Vinci F, Clerici E, Regalbuto C, Crapanzano C, Veraldi D, Moiraghi A, Marseglia GL. Efficacy of Anakinra on Multiple Coronary Arteries Aneurysms in an Infant with Recurrent Kawasaki Disease, Complicated by Macrophage Activation Syndrome. Children (Basel). 2022 May 5;9(5):672. doi: 10.3390/children9050672.
PubMed 35626849Maniscalco V, Abu-Rumeileh S, Mastrolia MV, Marrani E, Maccora I, Pagnini I, Simonini G. The off-label use of anakinra in pediatric systemic autoinflammatory diseases. Ther Adv Musculoskelet Dis. 2020 Oct 16;12:1759720X20959575. doi: 10.1177/1759720X20959575. eCollection 2020.
PubMed 33149772Gambacorta A, Buonsenso D, De Rosa G, Lazzareschi I, Gatto A, Brancato F, Pata D, Valentini P. Resolution of Giant Coronary Aneurisms in a Child With Refractory Kawasaki Disease Treated With Anakinra. Front Pediatr. 2020 May 7;8:195. doi: 10.3389/fped.2020.00195. eCollection 2020.
PubMed 32457855Mastrolia MV, Abbati G, Signorino C, Maccora I, Marrani E, Pagnini I, Simonini G. Early anti IL-1 treatment replaces steroids in refractory Kawasaki disease: clinical experience from two case reports. Ther Adv Musculoskelet Dis. 2021 Mar 29;13:1759720X211002593. doi: 10.1177/1759720X211002593. eCollection 2021.
PubMed 33854568