Anacomp. a Randomized Phase Iii Multicenter Trial Comparing the Efficacy and Safety of Anakinra Versus Intravenous Immunoglobulin (Ivig) Retreatment, in Patients with Kawasaki Disease WHO Failed to Respond to Initial Standard Ivig Treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

6 Jan 2026 → ongoing

Decision date (initial)

2024-11-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

DGOS (Direction Générale de l'Offre de Soins), Ministry of Health, France

External identifiers

EU CT number

2024-516244-25-00

EudraCT number

2020-003194-22

ClinicalTrials.gov

NCT04656184

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To compare the efficacy of Anakinra (IL-1R1 receptor antagonist) with 2nd IVIG infusion, in second line, on fever in patients with KD, who failed to respond to one infusion of IVIG (standard treatment).

Secondary objectives 6

1. Efficacy on fever at 72 hours
2. Efficacy on disease activity
3. Efficacy on KD symptoms
4. Efficacy on coronary lesions
5. Efficacy on inflammation
6. Safety and tolerability

Conditions and MedDRA coding

Kawasaki disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Children, male and female, from 12 months to <18 years old
2. Patient ≥ 7,5 kg
3. Patient with KD according to the American Heart Association definition for complete or incomplete KD. (Fever ≥ 5 days (or at least 3 days if KD with AHA criteria since the third days of fever) and ≥ 4 of 5 main clinical signs: modification of the extremities, polymorphic exanthema, and bilateral bulbar not exudative conjunctivitis, erythema of the lips or oral cavity, and cervical lymph nodes usually unilateral > 1.5 cm in diameter
4. Patients not responding to standard therapy for KD, i.e, persistence or recrudescence of fever (≥38°C) during the 24 to 48 hours following the end of the IVIG infusion (2g/kg).Patients with fever lasting at least 5 days (≥5 days) and up to 11 days inclusive (≤ 11days).
5. Patient, parents or legal guardian’s written informed consent is required
6. Patient with health insurance (SS or CMU)
7. Efficient contraception for the duration of participation in the research for childbearing aged women

Exclusion criteria 15

1. Preterm and neonates, pregnancy and breast feeding
2. Suspicion of another diagnosis
3. Patient with overt concomitant bacterial, viral or fungal infection
4. Patient previously treated with steroids and/or another biotherapy
5. Patient with increased risk of TB infection (e.g. close contact with a patient with tuberculosis, stay in a country with a high prevalence of tuberculosis for at least 3 months)
6. Recent tuberculosis infection or with active TB (e.g abnormal chest X-ray: systematized lung disease, non-systematized lung disease, diffuse infiltrative images, pleural effusion, adenopathy, cardiomegaly).
7. Patient with any type of immunodeficiency or cancer
8. Patients with severe renal impairment (CLcr < 30 ml/minute)
9. Patients with hepatic insufficiency
10. Patients with neutropenia (ANC<1.5 x109/l)
11. Patients included in another interventional protocol* Patient under the following treatments:
12. Immunosuppressive medications given in a period less than twice of their half-life prior the patient receives the study medication (systemic steroids, cyclosporine, tacrolimus, azathioprine, cyclophosphamide, interferon, mycophenolate, other anti-IL-1, anti IL-6, anti CD20 and anti TNF), plasmapheresis)
13. Hypersensitivity to anakinra (Kineret®) or excipients (citric acid, sodium chloride, disodium EDTA, polysorbate 80, sodium hydroxide, in water for injection)
14. Hypersensitivity to IV Ig (Privigen®), or excipients (L-proline and water for injection), hypersensitivity to human normal immunoglobulin, in particular if the patient have anti-IgA antibodies
15. Ongoing or recent use of any other medication Known inhibitors/inducers of cytochrome P450 as listed on the link below: http://medicine.iupui.edu/clinpharm/ddis/main-table

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The main criterion-evaluating efficacy in both groups is: the patient must reach a body (axillary (+0.5°C), tympanic, oral) temperature <38˚C within 2 days after initiation of treatment (considering time of the last escalation dose if any) (i.e. a binary outcome: success/failure).

Secondary endpoints 6

1. Temperature <38˚C within 3 days (72h) after initiation of treatment
2. Decrease of the CRP values from baseline to day 30 (CRP<6 mg/L at day 30)
3. Reduction in physician assessment of disease activity, on a 10 points scale, of at least to 50% between baseline and day 14.
4. Reduction in patient’s parent’s assessment of disease activity, on a 10 points scale, of to at least 50% between baseline and day 14.
5. Resolution of coronary abnormalities; i.e worst Z score <2.5, by echocardiogram if present at day 45.
6. Adverse events: pain/redness at injection site, bacterial infection, hepatitis, macrophage activation syndrome, severe neutropenia,

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Isabelle KONÉ-PAUT

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Malika Yahmi

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications