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Multicenter double-blind, randomized, placebo-controlled trial of IDEC-C2B8 for the treatment of childhood-onset nephrotic syndrome(JSKDC10) (JSKDC10)

Multicenter double-blind, randomized, placebo-controlled trial of IDEC-C2B8 for the treatment of childhood-onset nephrotic syndrome(JSKDC10)

Kazumoto Iijima

Kobe University Hospital

7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan

iijima@med.kobe-u.ac.jp

Naoko Kashiwagi

Kobe University Hospital

7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan

+81-78-382-6729

ctrcpj-jskdc10@med.kobe-u.ac.jp

COMPLETED

Nov. 01, 2018

Interventional

Randomized, Placebo-Controlled, Double-Blind Trial

double blind

Yes

3

(1) Diagnosed as idiopathic nephrotic syndrome (INS) according to the ISKDC criteria.
(2) First onset of INS is under 18 years of age.
(3) Subjects who are diagnosed as frequent recurrence or steroid dependency with recurrence just before registration and who can confirm the date of recurrence as the basis for diagnosis.
(4) Subjects who have not been treated with immunosuppressive treatment for INS.
(5) Diagnosed as steroid-sensitive relapse.
(6) CD20 positive B-cells >/= 5/mcL in the peripheral blood.
(7) Subjects can be hospitalized for treatments.
(8) Subjects have ability to provide written informed consent form. The written informed consent form of legal representative is also required for subjects less than 20 years of age.

(1) Subjects who have been diagnosed with steroid resistance NS.
(2) History of inflammatory nephritis such as IgA nephritis.
(3) Subjects falling under any of the following infectious diseases.
1) Subjects who have had a history of severe infection (pneumonia, pyelonephritis, etc.) requiring hospitalization within the past 6 months before registration.
2) Subjects who have had a history of opportunistic infection (cytomegalovirus infection, systemic fungal infection, pneumocystis infection, nontuberculous mycobacterial infection etc.) within 6 months before registration.
3) Subjects with active tuberculosis.
4) Subjects with or having suspected tuberculosis infection.
5) Subjects complicated with active hepatitis B or active hepatitis C, or patients confirmed to be hepatitis B virus carriers.
6) Subjects with confirmed HIV infection.
(4) Presence or history of angina pectoris, cardiac failure, myocardial infarction and/or serious arrhythmia grade 4 in "Common Terminology Criteria for Adverse Events (ver. 4.0)".
(5) Having received a live vaccine within 4 weeks prior to screening.
(6) Known hypertension which is uncontrollable with conventional anti-hypertensive.
(7) Deteriorated kidney function, e.g. estimated GFR<60mL/min./1.73m2.
(8) Presence or history of auto-immune diseases such as Hashimoto disease (Chronic thyroiditis), Crohn's disease, ulcerative colitis, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma or vascular purpura.
(9) Presence or history of cancer.
(10) History of organ transplantation.
(11) History of allergic reaction to acetaminophen and/or d-chlorpheniramine maleate.
(12) Subject falling under any of the following clinical laboratory findings.
1) WBC < 3,000/mcL
2) Neutrophil < 1,500/mcL
3) PLT < 50,000/mcL
4) AST(GOT) > 2.5 x ULN
5) ALT(GPT) > 2.5 x ULN
6) Positive for HBs antigen, HBs antibody, HBc antibody and HCV antibody
7) Positive for HIV antibody
(13) History of receiving any kinds of monoclonal antibody therapy.
(14) Having received any investigational agent within 6 months prior to enrollment, or participating other clinical studies.
(15) Subjects who do not agree with contraception during the study period (Negative HCG result is required at screening for female subjects after the first menstruation.).
(16) A female patient who is pregnant, has a possibility of pregnancy, or is breastfeeding.
(17) Judged inappropriate for this study by the physicians.

Both

Childhood onset idiopathic nephrotic syndrome showing frequent relapse or steroid dependence

Intervention type:DRUG Name of intervention:IDEC-C2B8 Dose form / Japanese Medical Device Nomenclature:INJECTION Route of administration / Site of application:INTRAVENOUS DRIP Dose per administration: 375 mg/m2 (but, maximum 500 mg/body) mg Dosing frequency / Frequency of use:QW 2 times Planned duration of intervention:2 times at an interval of 7 +/- 2 days Intended dose regimen:375 mg/m2 (but, maximum 500 mg/body) of the study drug given 2 times at an interval of 7 +/- 2 days detailes of teratment arms: Comparative intervention name:Placebo Dose form / Japanese Medical Device Nomenclature:INJECTION Route of administration / Site of application:INTRAVENOUS DRIP Dose per administration: 375 mg/m2 (but, maximum 500 mg/body) mg Dosing frequency / Frequency of use:QW 2 times Planned duration of intervention:2 times at an interval of 7 +/- 2 days Intended dose regimen:375 mg/m2 (but, maximum 500 mg/body) of the study drug given 2 times at an interval of 7 +/- 2 days

1. Efficacy outcome Relapse-free period 2. Safety endpoint Adverse event, Adverse drug reaction

1. Efficacy outcomes
(1) Time to treatment failure
(2) Total steroid dose
(3) Variation in B cell count during observational period
1) Measurement of B cell count
2) Duration of B-cell depletion
2. Other outcomes
(1) Relapse-free period in open-label phase
(2) Serum IDEC-C2B8 level
(3) Anti-rituximab antibody (human anti-chimeric antibody, HACA) in subject serum

+81-78-382-6669

+81-78-382-6690

July. 18, 2018

Yes

Will individual deidentified participant data (including data dictionaries) be available?: Yes. But mostly written in Japanese. Which data in particular will be shared?: Summary statistics. Because of the disease rarity, individual data will be disclosed carefully. Will additional, related documents be available: Yes. Study Protocol and Statistical Analysis Plan. Study Protocol is written in both Japanese and English, but Statistical Analysis Plan is written in Japanese. When will the data become available and for how long?: Beginning 3 months and ending 5 years following article publication and obtaining approval by PMDA. By what access criteria will the data be shared: Proposals should be directed to the clinical trial secretariat (iijima@med.kobe-u.ac.jp). To gain access, data requestors will need to sign a data access agreement.