Clinical Study of Rituximab for the Treatment for Idiopathic Membranous Nephropathy with Nephrotic Syndrome

Официальное название

The Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Rituximab (Genetical Recombination) for the Treatment for Idiopathic Membranous Nephropathy with Nephrotic Syndrome （PRIME Study）

Обзор

To confirm the efficacy and safety of rituximab (genetical recombination) intravenously administered to idiopathic membranous nephropathy with nephrotic syndrome.

Вмешательства

• Препарат Rituximab (genetical recombination)
  Administer 1,000 mg of rituximab (genetical recombination) IV infusion every two weeks for two doses in double-blind phase.
• Препарат Placebo
  Administer placebo IV infusion every two weeks for two doses in double-blind phase.
• Препарат Rituximab (genetical recombination)
  Patients who remain to be ICR II (Incomplete Remission Type II) or NR (No Response) until Week 26 in the double-blind phase, if the patients wish to move to the open-label phase and the investigator or a subinvestigator considers the move necessary, the patient will move to the open-label phase and receive 1,000 mg of rituximab (genetical recombination) IV infusion every two weeks for two doses after the readministration criteria are confirmed to be met.

Первичные конечные точки

• Percentage of patients achieving ICR I [Срок оценки: up to 26 weeks]

Вторичные конечные точки (7)

• Percentage of patients who are CR, ICR I, ICR II, NR or PR [Срок оценки: up to 26 weeks]
• Duration before achieving CR, ICR I, ICR II or PR [Срок оценки: up to 26 weeks]
• Urine protein-creatinine ratio [Срок оценки: up to 26 weeks]
• eGFR [Срок оценки: up to 26 weeks]
• B-cells (CD19-positive and CD20-positive cells) [Срок оценки: up to 26 weeks]
• Expression of HACA [Срок оценки: up to 26 weeks]
• Serum rituximab (genetical recombination) concentration [Срок оценки: up to 26 weeks]

Критерии участия

Критерии включения

• Patients who undergo kidney biopsy and are diagnosed as having idiopathic membranous nephropathy prior to the obtainment of informed consent
• Patients who are diagnosed as having nephrotic syndrome prior to the obtainment of informed consent and receive no steroids or immunosuppressants within 12 weeks prior to the obtainment of informed consent
• Patients with urine protein-creatinine ratio ≥ 3.5 g/gCr at the screening
• Patients with hypoalbuminemia (serum albumin ≤ 3.0 g/dL) at the screening
• Patients aged 15 years or older at informed consent
• Patients who give voluntary written consent after having received adequate information on this study (legally acceptable representatives should also give consent for underage patients, and informed assent should be obtained from children)

Критерии исключения

• Patients with primary nephrotic syndrome other than membranous nephropathy (IgA nephropathy, minimal change disease, focal segmental glomerulosclerosis and so forth), and patients with secondary nephrotic syndrome (autoimmune disease, metabolic disease, infection, allergic/hypersensitive disease, tumor, and drug-induced disease)
• Patients with the renal function lowered (eGFR <30 mL/min/1.73 m2 based on CKD-EPIcr formula) at the screening
• Patients who have used anti-CD20 antibody including rituximab (genetical recombination) prior to the informed consent for idiopathic membranous nephropathy
• Patients who have participated in another clinical study within 12 weeks prior to the informed consent (enrollment is allowed for those participating in a clinical study in the range of 'Indications' or 'Dosage and Administration' in Japan) or patients who are participating in another study
• Patients with history of renal transplant
• Patients with poorly controlled diabetes (HbA1c of 8.0% or higher)
• Patients who have or are suspected to have active infection (infection requiring treatment with systemic antimicrobial, antifungal, or antiviral agents) at the time of informed consent
• Patients tested positive for HBs antigen, HBs antibody, HBc antibody, and/or HCV antibody (patients with positive HBs antibody and/or HBc antibody can be enrolled only when HBV-DNA test is negative \[less than the detection limit\]), or patients with positive HIV antibody or HTLV-1 antibody at the time of the screening
• Patients with leukopenia (less than 2,000 /mm3), neutropenia (less than 1,000 /mm3), or lymphopenia (less than 500 /mm3) at the time of the screening
• Patients with history of serious hypersensitivity or anaphylactic reaction to one of the ingredients in the investigational drug or murine protein-containing products
• Patients who are judged to be life-threatening nephrotic syndrome by the investigator or a subinvestigator
• Patients with serious comorbidity (e.g., hepatic, renal (excluding idiopathic membranous nephropathy with nephrotic syndrome), cardiac, lung, hematologic, or brain disease)
• Female patients who are pregnant, lactating, or potentially pregnant, patients who are not willing to use contraceptive measures during the study period, or female patients not willing to use contraceptive measures until 12 months after the last dose of study drug (except for female patients who are unale to pregnant)
• Patients who are judged to be unsuitable by the investigator or a subinvestigator

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Япония · 18 центров

• Anjo Kosei Hospital — Anjo
• Kasugai Municipal Hospital — Kasugai
• Konan Kosei Hospital — Kōnan
• Nagoya University Hospital — Nagoya
• Fujita Health University hospital — Toyoake
• Juntendo University Urayasu Hospital — Urayasu
• Kyushu University Hospital — Fukuoka
• Kurume University Hospial — Kurume
• … и ещё 10 центров

Публикации

• Shimizu S, Tanaka A, Matsuyama N, Kinoshita F, Furuhashi K, Maruyama S; PRIME Study Group. Randomised, double-blind study to evaluate the efficacy of rituximab in the treatment of idiopathic membranous nephropathy: A clinical trial protocol. PLoS One. 2025 Mar 18;20(3):e0320070. doi: 10.1371/journal.pone.0320070. eCollection 2025. PMID 40100934
• Larkins NG, Hahn D, Liu ID, Willis NS, Craig JC, Hodson EM. Non-corticosteroid immunosuppressive medications for steroid-sensitive nephrotic syndrome in children. Cochrane Database Syst Rev. 2024 Nov 8;11(11):CD002290. doi: 10.1002/14651858.CD002290.pub6. PMID 39513526

Идентификаторы

NCT: NCT05914155 · CAMCR-020

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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