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

Phase 3

Recruiting

• Conditions: Glomerulonephritis, Membranous; Nephrotic Syndrome，Idiopathic
• Interventions: Drug: Rituximab (genetical recombination); Drug: Placebo

• Registration Number: NCT05914155
• Lead Sponsor: Shoichi Maruyama MD PhD

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-06-13
• Study First Submitted QC: 2023-06-13
• Study First Posted: 2023-06-22
• Study Start: 2023-06-24
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-09
• Last Update Posted: 2025-02-11
• Primary Completion: 2027-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 88

Inclusion Criteria

1. Patients who undergo kidney biopsy and are diagnosed as having idiopathic membranous nephropathy prior to the obtainment of informed consent
2. 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
3. Patients with urine protein-creatinine ratio ≥ 3.5 g/gCr at the screening
4. Patients with hypoalbuminemia (serum albumin ≤ 3.0 g/dL) at the screening
5. Patients aged 15 years or older at informed consent
6. 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)

Exclusion Criteria

1. 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)
2. Patients with the renal function lowered (eGFR <30 mL/min/1.73 m2 based on CKD-EPIcr formula) at the screening
3. Patients who have used anti-CD20 antibody including rituximab (genetical recombination) prior to the informed consent for idiopathic membranous nephropathy
4. 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
5. Patients with history of renal transplant
6. Patients with poorly controlled diabetes (HbA1c of 8.0% or higher)
7. 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
8. 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
9. 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
10. Patients with history of serious hypersensitivity or anaphylactic reaction to one of the ingredients in the investigational drug or murine protein-containing products
11. Patients who are judged to be life-threatening nephrotic syndrome by the investigator or a subinvestigator
12. Patients with serious comorbidity (e.g., hepatic, renal (excluding idiopathic membranous nephropathy with nephrotic syndrome), cardiac, lung, hematologic, or brain disease)
13. 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)
14. Patients who are judged to be unsuitable by the investigator or a subinvestigator

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rituximab group in double-blind phase	Rituximab (genetical recombination)	-
Rituximab group in open-label phase	Rituximab (genetical recombination)	-
Placebo group in double-blind phase	Placebo	-

Primary Outcome Measures

Name	Time	Method
Percentage of patients achieving ICR I	up to 26 weeks	Achieving ICR I is defined as "Urine protein-creatinine ratio \< 1.0 g/gCr".

Secondary Outcome Measures

Name	Time	Method
Duration before achieving CR, ICR I, ICR II or PR	up to 26 weeks	Duration of achieving CR, ICR I, ICR II or PR is summarized.
eGFR	up to 26 weeks	The differences of eGFR between prior to treatment and at each timepoint are summarized.
B-cells (CD19-positive and CD20-positive cells)	up to 26 weeks	B cell counts (CD19 positive and CD20 positive cell counts) at each timepoint are summarized.
Percentage of patients who are CR, ICR I, ICR II, NR or PR	up to 26 weeks	CR, ICR I, ICR II, NR or PR are defied as below; CR (Complete Remission): Urine protein-creatinine ratio \< 0.3 g/gCr ICR I (Incomplete Remission Type I): 0.3 g/gCr ≤ Urine protein-creatinine ratio \< 1.0 g/gCr ICR II (Incomplete Remission Type II): 1.0 g/gCr ≤ Urine protein-creatinine ratio \< 3.5 g/gCr NR (No Response): 3.5 g/gCr ≤ Urine protein-creatinine ratio PR (Partial Remission): Decrease in urine protein-creatinine ratio from base line ≥50%, and urine protein-creatinine ratio 0.3 to 3.5 g/gCr
Expression of HACA	up to 26 weeks	The number of patients expressing HACA, and the proportion of these patients at each timepoint are summarized.
Serum rituximab (genetical recombination) concentration	up to 26 weeks	Serum rituximab (genetical recombination) level at each timepoint are summarized.
Urine protein-creatinine ratio	up to 26 weeks	The differences of urine protein-creatinine ratio between prior to treatment and at each timepoint are summarized.

Trial Locations

Locations (18)

Osaka University Hospital; 🇯🇵 Osaka, Japan

Tohoku University Hospital; 🇯🇵 Sendai, Miyagi, Japan

Kasugai Municipal Hospital; 🇯🇵 Kasugai, Aichi, Japan

Kumamoto University Hospital; 🇯🇵 Kumamoto, Japan

Konan Kosei Hospital; 🇯🇵 Kōnan, Aichi, Japan

Juntendo University Urayasu Hospital; 🇯🇵 Urayasu, Chiba, Japan

Kyushu University Hospital; 🇯🇵 Fukuoka, Japan

Nagoya University Hospital; 🇯🇵 Nagoya, Aichi, Japan

Kurume University Hospial; 🇯🇵 Kurume, Fukuoka, Japan

Asahikawa Medical University Hospital; 🇯🇵 Asahikawa, Hokkaido, Japan

Mie University Hospial; 🇯🇵 Tsu, Mie, Japan

Hamamatsu University Hosptial; 🇯🇵 Hamamatsu, Shizuoka, Japan

University Hospital,Kyoto Prefectural University of Medicine; 🇯🇵 Kyoto, Japan

Kyoto University Hospital; 🇯🇵 Kyoto, Japan

Fujita Health University hospital; 🇯🇵 Toyoake, Aichi, Japan

Kanazawa University Hospital; 🇯🇵 Kanazawa, Ishikawa, Japan

Anjo Kosei Hospital; 🇯🇵 Anjo, Aichi, Japan

Tazuke Kofukai, Medical Research Institute, Kitano Hospital; 🇯🇵 Osaka, Japan