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Multicenter single-armed clinical trial of combination therapy with IDEC-C2B8 and steroid pulse therapy for childhood-onset refractory steroid-resistant nephrotic syndrome (JSKDC11) (JSKDC11)

Multicenter single-armed clinical trial of combination therapy with IDEC-C2B8 and steroid pulse therapy for childhood-onset refractory steroid-resistant nephrotic syndrome (JSKDC11) (JSKDC11)

Nozu Kandai

Kobe University Hospital

7-5-2 Kusunoki-cho, Chuo-ku, Kobe

nozu@med.kobe-u.ac.jp

Nozu Kandai

Kobe University Hospital

7-5-2 Kusunoki-cho, Chuo-ku, Kobe

+81-78-382-6090

nozu@med.kobe-u.ac.jp

Not Recruiting

May. 21, 2019

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

(1) Patients with idiopathic nephrotic syndrome of childhood onset (The diagnostic criteria of idiopathic nephrotic syndrome in the initial diagnosis refer to the criteria of International Pediatric Kidney Disease in Childhood (ISKDC).)
(2) Patients younger than 18 years at the onset of idiopathic nephrotic syndrome
(3) Patients with steroid-resistant nephrotic syndrome who have been treated with both 1) and 2) below within 1 year prior to enrollment
1) Treated by calcineurin inhibitor (Cyclosporine and tacrolimus) at least more than 2 months within 4 months before the registration
2) Treated by steroid pulse therapy (3 to 12 times)
However, patients who, within 1 year prior to enrollment, received 3 or more steroid pulse therapy and were treated with a calcineurin inhibitor (Cyclosporine and tacrolimus) for at least 1 month within 4 months before the registration and requires at least 6 days of albumin infusion per week to manage edema, and were unable to continue treatment with both 1) and 2) can be included to this study.
(4) Patients with a urinary protein-creatinine ratio of 2.0 g/g Cr or greater and a serum albumin level of 2.5 g/dL or less in any of the 2 measurements conducted within 4 weeks prior to enrollment.
The second measurement date must be more than 7 days after the first measurement date.
(5) Patients with at least CD 20 positive cells of 5/microL in the peripheral blood
In facilities where the number of CD 20 positive cells cannot be measured, even CD 19 positive cells can be measured
(6) Patients who can be admitted to the hospital for 2 days and 1 night from the day of administration to the day following the scheduled date of the first administration of IDEC-C2B8 and who can visit the hospital throughout the observation period
(7) Patients who are 20 years of age or older, or patients who are younger than 20 years of age whose legally acceptable representative (Person who has parental authority or legal guardian of the patient) has provided adequate information about the study and has given written consent to participate in the study (However, in patients between the ages of 16 and 20, written consent from the patient to participate in the study should be obtained.)

(1) Patients who have been diagnosed with nephritic nephrotic syndrome such as IgA nephropathy by enrollment, or who are suspected of having secondary nephrotic syndrome
(2) Patients with or suspected of having a genetic abnormality associated with the onset of nephrotic syndrome
(3) Patients who have used new immunosuppressive drugs (including high-dose steroid steroid therapy) within 4 weeks before registration, or patients whose dose of immunosuppressants or prednisolone were increased within 4 weeks before registration (However, the increase in blood concentration adjustment of calcineurin inhibitor is allowed).
(4) Patients who fall under any of the following 1) to 6) infections
1) Patients with severe infections (pneumonia, pyelonephritis, etc.) that require hospitalization or a history of infection within 6 months prior to registration
2) Patients who have an opportunistic infection (cytomegalovirus infection, systemic fungal infection, pneumocystis infection, non-tuberculous mycobacterial infection etc.) or have a history of these infections 6 months before registration
3) Patients with active tuberculosis
4) Patients who have or are suspected of having TB infection
5) Patients with active hepatitis B or active hepatitis C, or patients confirmed to be hepatitis B virus carriers
6) Patients with HIV infection
(5) Angina pectoris, heart failure, myocardial infarction, or advanced arrhythmia (adverse event common term standard v4.0 Japanese translation JCOG version
(6) Patients received live vaccination within 4 weeks before registration
(7) Patients with uncontrolled hypertension even if they are treated with antihypertensive drugs at the time of enrollment
(8) Autoimmune disease (Hashimoto's disease [chronic thyroiditis], Crohn's disease, ulcerative colitis, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma etc.) Or patients with IgA vasculitis, or patients with a history of these
(9) Patients with malignancy (excluding suspects for which no definitive diagnosis has been made), or patients with a history of malignancy
(10) Patients who have received organ transplantation (except for cornea and hair transplantation etc.)
(11) Patients with a history of drug allergy to methylprednisolone, acetaminophen and d-chlorpheniramine maleate
(12) Patients with renal dysfunction (eGFR less than 45 mL / min / 1.73 m2) at enrollment
(13) Patients who meet any one of the following 1) to 7) clinical examination items at the time of registration. Measurement values shall be measured after consent or within 2 weeks before registration.
1) White blood cells: <3,000 / microL
2) Neutrophils: <1,500 / microL
3) Platelet: <50,000 / microL
4) AST (GOT): at least 2.5 times the upper limit of the reference value
5) ALT (GPT): at least 2.5 times the upper limit of the reference value
6) HBs antigen, HBs antibody, HBc antibody, HCV antibody: either is positive
However, among HBs antibody only positive patients, HBV vaccination history and HBV-DNA quantification at the time of enrollment (-): Excluding patients with less than detection sensitivity
7) HIV antibody: positive
(14) Patients who used monoclonal antibodies other than IDEC-C2B8 (whether mouse, rat, chimera, or human)
(15) Patients who used IDEC-C2B8 within 1 year before registration
(16) Patients who have received other clinical trialed drugs within 6 months prior to enrollment, or who are planning to participate in other investigations during the study participation period
(17) In the case of the age at which pregnancy is possible, patients who do not agree to contraception during the observation period (confirmation by serum HCG test at screening is mandatory)
(18) Female patients who are pregnant or who are possibly pregnant or who are nursing
(19) Patients who were judged to be ineligible for this trial

Both

Childhood onset refractory steroid-resistant nephrotic syndrome

Steroid pulse therapy (1 course; 3 consecutive days of methylprednisolone sodium succinate 30 mg / kg / day for a maximum of 5 courses) combined with IDEC-C2B8 (4 doses of 375 mg / m2 / dose at 1 week intervals)

Rituximab, SRNS

More than 50% reduction of urinary protein creatinine ratio from baseline at Day 169

(1) More than 50% reduction of urinary protein creatinine ratio from baseline at Day 169 and the urinary protein creatinine ratio is 0.2 g / g to 2.0 g / gC.
(2) Complete remission at Day 169
(3) Incomplete remission at Day 169
(4) Either incomplete remission (incomplete remission and complete remission at Day 169.
(5) Time to incomplete remission
(6) Time to complete remission
(7) Nephrotic status at Day 169
(8) Chronic renal failure development during the observation period
(9) Urinary protein creatinine ratio at each evaluation time point
(10) Estimated glomerular filtration rate at each evaluation point
(11) Serum albumin at each evaluation time point
(12) Peripheral blood B cell depletion period

+81-78-382-6669

April. 17, 2019

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. Those are 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 (nozu@med.kobe-u.ac.jp). To gain access, data requestors will need to sign a data access agreement.

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