The efficacy of IDEC-C2B8 treatment for early-stage pediatric nephrotic syndrome

JRCT ID: jRCT2051240106

Registered date:07/08/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Childhood-onset idiopathic nephrotic syndrome
• Date of first enrollment: 01/10/2024
• Target sample size: 40
• Study type: Interventional

Intervention(s)

<Standard treatment group>
Prednisolone for relapse immediately prior to enrollment will be continued and completed. After completion of prednisolone administration, patients will be followed without treatment during the observation period (until Day 533) until a relapse is observed. If relapse is observed during the observation period, prednisolone should be administered.
<Investigational Drug Group>
Prednisolone for relapse immediately prior to enrollment will be continued and completed. The first dose of study drug will be administered within 14 days of enrollment (Day 1), followed by a second dose 1 week later. After completion of the study drug and prednisolone administration, patients will be followed without treatment during the observation period (up to Day 533) until a relapse is observed. If relapse is observed during the observation period, prednisolone should be administered.

Outcome(s)

• Primary Outcome: Relapse-free period

Secondary Outcome

<Secondary Endpoint>
1. Time to development to frequently-relapsing nephrotic syndrome
2. Time to development to steroid-dependent nephrotic syndrome
3. Time to development to steroid resistant nephrotic syndrome
4. Time to development to frequently-relapsing nephrotic syndrome or steroid dependent nephrotic syndrome
5. Total steroid dosage

<Other Endpoint>
1. Peripheral blood B-cell depletion period
2. HACA production ratio
3. IDEC-C2B8 blood concentration
4. Association between depletion of B cells in peripheral blood and first recurrence
5. Association between HACA production and first recurrence
6. Association of anti-nephrin antibody with first relapse
7. Association between NPHS1 polymorphism and anti-nephrin antibody

<Safety endpoint>
1. Adverse event, Adverse drug reaction
2. Clinical laboratory values, Vital signs

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Fulfill the diagnostic criteria of idiopathic NS (the International Study of Kidney Disease in Children [ISKDC] idiopathic NS diagnostic criteria are used as a reference during the patient's initial diagnosis).
2. Younger than 18 years at the time of onset of idiopathic NS.
3. Steroid sensitive at the first onset.
4. The first relapse occurred within 6 months after the initial remission, and the patients with confirmed steroid sensitivity at the relapse.
5. No history of treatment with any immunosuppressant for NS.
6. Achieving remission within 3 weeks of the first relapse by standard steroid treatment.
7. CD20-positive cell count of at least 5/mcL in peripheral blood.
8. Ability to stay in the hospital overnight on all days of planned investigational drug administration.
9. Provision of consent by the patient (aged 18 years or older) or a legal representative (parents or legal guardians) using a document approved by the institutional review board after receiving an adequate explanation regarding the implementation of this clinical trial.

Exclude criteria

1. Diagnosis of SRNS.
2. Diagnosis of nephritic or secondary NS.
3. History of severe infections such as pulmonary tuberculosis, deep mycosis, human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) or other active viral infections.
4. History of angina pectoris, cardiac failure, myocardial infarction, or serious arrhythmia.
5. Receipt of a live vaccine within 4 weeks prior to assignment.
6. Poorly controlled hypertension.
7. Impaired renal function.
8. Diagnosis of autoimmune diseases, or systemic lupus nephritis.
9. Active IgA vasculitis.
10. History of malignant tumors.
11. History of organ transplantation (excluding corneal and hair transplants).
12. Allergy to methylprednisolone, acetaminophen, or D-chlorpheniramine maleate.
13. Any of the following abnormal clinical laboratory values at the time of registration.
1) Leukocytes, < 3000/mcL
2) Neutrophils, < 1500/mcL
3) Platelets, < 50,000/mcL
4) Aspartate aminotransferase (AST) > 2.5 x ULN
5) Alanine aminotransferase (ALT) > 2.5 x ULN
6) Positive for hepatitis B surface (HBs) antigen, HBs antibody, hepatitis B core antibody, or HCV antibody
7) Positive for HIV antibody positivity.
14. Prior receipt of monoclonal antibodies of any type (mouse, rat, chimeric or human).
15. Prior receipt of other investigational drugs within 6 month before assignment or participation in other studies at the time of assignment.
16. Patients who do not agree to use contraception during the observation period.
17. Female patients who are pregnant, breastfeeding, or capable of becoming pregnant (confirmation by serum human chorionic gonadotropin test is required during screening).
18. Assessed to be unfit for participation by the investigators.

Related Information

• Primary Sponsor: Yamamura Tomohiko
• Secondary Sponsor: Nozu Kandai,Nakanishi Koichi,Sako Mayumi,Horinouchi Tomoko
• Source(s) of Monetary Support: Zenyaku Kogyo Co., Ltd.