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

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

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).

Study Overview

• Status: Completed
• Conditions: Kawasaki Disease
• Intervention / Treatment: Drug: Immunoglobulin G; Drug: Acetylsalicylic acid

Detailed Description

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%.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Anyang, Korea, Republic of
    • Hallym University Sacred Heart Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • The Catholic University of Korea Seoul St. Mary's Hospital
  • Seoul, Korea, Republic of
    • Kyung Hee University Hospital at Gangdong
  • Seoul, Korea, Republic of
    • Kyung Hee University Medical Center
  • Seoul, Korea, Republic of
    • Severance Hospital
  • Wonju, Korea, Republic of
    • Wonju Severance Christian Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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)

2. 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

3. Subjects whose subject's parents or legally authorized representative gave voluntary written consent to participate in the clinical trial

Exclusion Criteria:

1. Subjects with a history of KD

2. 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

3. Subjects who are currently receiving or who have received any investigational drug or device within 30 days prior to administration of the IP
4. Subjects who have received TNF alpha antagonist or systemic corticosteroids within 48 hours prior to administration of the IP
5. 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.)
6. Subjects who have received immunosuppressive or immunomodulatory drugs within 3 months prior to administration of the IP
7. Subjects with immunodeficiency including known positive serology for human immunodeficiency virus (HIV)
8. Subjects with a history of hypersensitivity or shock to IVIG formulations
9. Subjects with underlying liver disease or liver dysfunction with known etiology
10. Subjects with renal impairment whose creatinine level is more than twice the upper limit of the normal range
11. Subjects with a history of malignant tumor
12. Subjects with a history of IgA deficiency
13. Subjects who are considered by the investigator to be an unsuitable candidate for the study for any reason

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Green Cross Corporation
• Investigators: Principal Investigator: Mi Young Han, MD, Ph.D., Kyunghee University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Actual): November 22, 2019
• Study Completion (Actual): November 22, 2019

Study Registration Dates

• First Submitted: May 16, 2019
• First Submitted That Met QC Criteria: June 27, 2019
• First Posted (Actual): July 1, 2019

Study Record Updates

• Last Update Posted (Actual): May 21, 2020
• Last Update Submitted That Met QC Criteria: May 21, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Lymphatic Diseases; Vasculitis; Skin Diseases, Vascular; Mucocutaneous Lymph Node Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Immunologic Factors; Aspirin; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; Immunoglobulin G
• Other Study ID Numbers: GC5107E

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No