Clinical trial NCT05914155: Clinical Study of Rituximab for the Treatment for Idiopathic Membranous Nephropathy with Nephrotic Syndrome
Official title: 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）
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Glomerulonephritis, Membranous
Nephrotic Syndrome，Idiopathic
Lead sponsor: Nagoya University
Sponsor class: OTHER
First posted: 2023-06-22
Enrollment: 88
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of patients achieving ICR I
timeFrame: up to 26 weeks
Secondary outcomes:
measure: Percentage of patients who are CR, ICR I, ICR II, NR or PR
timeFrame: up to 26 weeks
measure: Duration before achieving CR, ICR I, ICR II or PR
timeFrame: up to 26 weeks
measure: Urine protein-creatinine ratio
timeFrame: up to 26 weeks
measure: eGFR
timeFrame: up to 26 weeks
measure: B-cells (CD19-positive and CD20-positive cells)
timeFrame: up to 26 weeks
measure: Expression of HACA
timeFrame: up to 26 weeks
measure: Serum rituximab (genetical recombination) concentration
timeFrame: up to 26 weeks
Other outcomes:
Locations:
city: Anjo
country: Japan
facility: Anjo Kosei Hospital
state: Aichi
city: Kasugai
country: Japan
facility: Kasugai Municipal Hospital
state: Aichi
city: Kōnan
country: Japan
facility: Konan Kosei Hospital
state: Aichi
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Toyoake
country: Japan
facility: Fujita Health University hospital
state: Aichi
city: Urayasu
country: Japan
facility: Juntendo University Urayasu Hospital
state: Chiba
city: Kurume
country: Japan
facility: Kurume University Hospial
state: Fukuoka
city: Asahikawa
country: Japan
facility: Asahikawa Medical University Hospital
state: Hokkaido
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
state: Ishikawa
city: Tsu
country: Japan
facility: Mie University Hospial
state: Mie
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Hamamatsu
country: Japan
facility: Hamamatsu University Hosptial
state: Shizuoka
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Kyoto
country: Japan
facility: University Hospital,Kyoto Prefectural University of Medicine
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Osaka
country: Japan
facility: Tazuke Kofukai, Medical Research Institute, Kitano Hospital
city: Osaka
country: Japan
facility: Osaka University Hospital
Study officials:
affiliation: Nagoya University Hospital
name: Shoichi Shoichi, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References: