Study of Combined Therapy IVIG-SN 10% and Acetylsalicylic Acid in Kawasaki Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of high-dose human Immunoglobulin G Intravenous (IGIV) 10% in subjects with Kawasaki diseases (KD).

Detailed Description
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This is a multicenter, single-arm, and open-label clinical trial to evaluate the coronary artery lesions (CALs) at 2 and 7 weeks after single dose of IGIV 10% (2 g/kg) administration for at least 12 hours to evaluate the efficacy and safety of IGIV 10%.

Official Title
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Multicenter, Single-arm, Phase IV Study to Evaluate the Efficacy, Safety of Combined Therapy of Aspirin and IVIG-SN 10% in Pediatric Patients With Kawasaki Disease

Conditions
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Kawasaki Disease

Intervention / Treatment
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* Drug: Immunoglobulin G
* Drug: Acetylsalicylic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants and children aged 3 months to 7 years inclusive, at the time of signing the informed consent, however, patients with complete KD are eligible up to 12 years (applies to 2A) Subjects with fever 4-10 days meeting one of following criteria (A, B or C) A. Subjects with at least 4 of the following principal clinical findings: i) Bilateral bulbar conjunctival injection without exudate ii) Erythema and cracking of lips, strawberry tongue, and/or erythema of oral and pharyngeal mucosa iii) Erythema and edema of the hands and feet in acute phase and/or periungual desquamation in subacute phase iv) Cervical lymphadenopathy (≥1.5 cm diameter), usually unilateral v) Rash: maculopapular, diffuse erythroderma, or erythema multiforme-like B. Subjects with at least 3 of the principal clinical findings and coronary artery abnormalities detected by 2-dimensional echocardiography: Z score of left anterior descending coronary artery or right coronary artery ≥2.5 C. Subjects without coronary artery abnormalities, but with fever ≥5 days, 2 or 3 of the principal clinical findings , CRP of ≥3.0 mg/dL and meeting 3 or more of the following laboratory findings: i) Albumin <3.0 g/dL ii) Anemia for age iii) Elevated alanine aminotransferase level iv) Platelet count of >450,000/mm3 after the 7th day of fever v) White blood cell count of >15,000/mm3 vi) Urine >10 white blood cells/high-power field Subjects whose subject's parents or legally authorized representative gave voluntary written consent to participate in the clinical trial Exclusion Criteria: Subjects with a history of KD Subjects with following laboratory findings: A. Platelet count <100,000/mm3 B. WBC count <3,000 cells/mm3 C. hemoglobin, hematocrit or red blood cell count more than 30% above the upper limit or 30% below the lower limit of the normal range Subjects who are currently receiving or who have received any investigational drug or device within 30 days prior to administration of the IP Subjects who have received TNF alpha antagonist or systemic corticosteroids within 48 hours prior to administration of the IP Subjects who are considered by the investigator to be an unsuitable candidate for the study due to a severe chronic disease (e.g. cardiovascular disease except controllable hypertension, respiratory disease with respiratory failure, metabolic disease, renal failure, hemoglobinopathy, etc.) Subjects who have received immunosuppressive or immunomodulatory drugs within 3 months prior to administration of the IP Subjects with immunodeficiency including known positive serology for human immunodeficiency virus (HIV) Subjects with a history of hypersensitivity or shock to IVIG formulations Subjects with underlying liver disease or liver dysfunction with known etiology Subjects with renal impairment whose creatinine level is more than twice the upper limit of the normal range Subjects with a history of malignant tumor Subjects with a history of IgA deficiency Subjects who are considered by the investigator to be an unsuitable candidate for the study for any reason

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Investigational product (IP) | Drug: Immunoglobulin G<br>* single dose of IGIV 10% (2 g/kg) administered intravenously for at least 12 hours<br>Drug: Acetylsalicylic acid<br>* Coadministration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of CALs | incidence of CALs at 7 weeks after treatment | 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of CALs | incidence of CALs at 2 weeks after treatment | 2 weeks | 
| total duration of fever | total duration of fever after treatment | baseline | 
| laboratory measurements : markers of inflammation and cardiovascular disease | measurement of erythrocyte sedimentation rate (ESR) | 7 weeks | 
| laboratory measurements : markers of inflammation and cardiovascular disease | measurement of C-reactive protein (CRP) | 7 weeks | 
| laboratory measurements : markers of inflammation and cardiovascular disease | measurement of N-terminal pro B-type natriuretic peptide (NTproBNP) or B-type natriuretic peptide (BNP) | 7 weeks | 
| laboratory measurements : markers of inflammation and cardiovascular disease | measurement of creatine kinase-myocardial band (CK-MB) | 7 weeks | 
| laboratory measurements : markers of inflammation and cardiovascular disease | measurement of procalcitonin | 7 weeks | 
| laboratory measurements : markers of inflammation and cardiovascular disease | measurement of soluble suppression of tumorigenicity 2 (sST2) | 7 weeks | 
| laboratory measurements : markers of inflammation and cardiovascular disease | measurement of Troponin I | 7 weeks | 
| IGIV resistance | frequency of IGIV resistance | baseline | 
| adverse events, adverse drug reactions and serious adverse events | number of adverse events, adverse drug reactions and serious adverse events | 7 weeks | 
| laboratory measurements : hematological parameters | measurement of white blood cell (WBC) | 7 weeks | 
| laboratory measurements : hematological parameters | measurement of red blood cell (RBC) | 7 weeks | 
| laboratory measurements : hematological parameters | measurement of hemoglobin | 7 weeks | 
| laboratory measurements : hematological parameters | measurement of hematocrit | 7 weeks | 
| laboratory measurements : hematological parameters | measurement of platelet count | 7 weeks | 
| laboratory measurements : clinical chemistry parameters | measurement of alanine transaminase (ALT) | 7 weeks | 
| laboratory measurements : clinical chemistry parameters | measurement of albumin | 7 weeks | 
| laboratory measurements : urinalysis | measurement of WBC (urine microscopy) | 7 weeks | 
| vital signs: blood pressure | measurement of systolic and diastolic blood pressure | 7 weeks | 
| vital signs: body temperature | measurement of body temperature | 7 weeks | 
| physical examination | visual inspection of general appearance, head, eyes, nose-mouth-throat, lymph nodes, skin, extremities for abnormal findings | 7 weeks |