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

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）

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

Study Overview

• Status: Recruiting
• Conditions: Glomerulonephritis, Membranous; Nephrotic Syndrome，Idiopathic
• Intervention / Treatment: Drug: Rituximab (genetical recombination); Drug: Rituximab (genetical recombination); Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 88
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Shoichi Maruyama, PhD, MD; Phone Number: +81527442192; Email: marus@med.nagoya-u.ac.jp
• Study Contact Backup: Name: Shinobu Shimizu, PhD; Phone Number: +81527442942; Email: shimizu.shinobu.w3@f.mail.nagoya-u.ac.jp

Study Locations

• Japan
  • Fukuoka, Japan, 8128582
    • Recruiting
    • Kyushu University Hospital
    • Contact: Toshiaki Nakano, PhD, MD; Phone Number: +81926425256; Email: nakano.toshiaki.455@m.kyushu-u.ac.jp
    • Contact: Kenji Ueki, PhD, MD; Phone Number: +81926425256; Email: ueki.kenji.982@m.kyushu-u.ac.jp
  • Kumamoto, Japan, 8608556
    • Recruiting
    • Kumamoto University Hospital
    • Contact: Hideki Yokoi, PhD, MD; Phone Number: +81963442111
  • Kyoto, Japan, 6028566
    • Recruiting
    • University Hospital,Kyoto Prefectural University of Medicine
    • Contact: Tetsuro Kusaba, PhD, MD; Phone Number: +81752515111; Email: kusaba@koto.kpu-m.ac.jp
  • Kyoto, Japan, 6068507
    • Recruiting
    • Kyoto University Hospital
    • Contact: Shigenori Yamamoto, PhD, MD; Phone Number: +81757513111
  • Osaka, Japan, 5650871
    • Recruiting
    • Osaka University Hospital
    • Contact: Yoshitaka Isaka, PhD, MD; Phone Number: +81668795111
  • Osaka, Japan, 5308480
    • Recruiting
    • Tazuke Kofukai, Medical Research Institute, Kitano Hospital
    • Contact: Tatsuo Tsukamoto, PhD, MD; Phone Number: +81663121221
  • Aichi
    • Anjo, Aichi, Japan, 4468602
      • Recruiting
      • Anjo Kosei Hospital
      • Contact: Nobuhide Endo, PhD, MD; Phone Number: +81566752111; Email: ennob08@yahoo.co.jp
    • Kasugai, Aichi, Japan, 486-8510
      • Recruiting
      • Kasugai Municipal Hospital
      • Contact: Yosuke Saka, PhD, MD; Phone Number: +81568570057; Email: yosukesaka@hospital.kasugai.aichi.jp
      • Contact: Toshiaki Sawada; Phone Number: +81568570057; Email: chikenjimukyoku@hospital.kasugai.aichi.jp
    • Kōnan, Aichi, Japan, 4838704
      • Recruiting
      • Konan Kosei Hospital
      • Contact: Hiroshi Kojima, PhD, MD; Phone Number: +81587513333; Email: h-kojima@konan.jaaikosei.or.jp
    • Nagoya, Aichi, Japan, 4668560
      • Recruiting
      • Nagoya University Hospital
      • Contact: Akihito Tanaka, PhD, MD; Phone Number: +81527442111; Email: tanaka17@med.nagoya-u.ac.jp
    • Toyoake, Aichi, Japan, 4701192
      • Recruiting
      • Fujita Health University Hospital
      • Contact: Naotake Tsuboi, PhD, MD; Phone Number: +81562932111; Email: nao-take@fujita-hu.ac.jp
      • Contact: Michiko Nakano; Phone Number: +81562932139; Email: nakanom@fujita-hu.ac.jp
  • Chiba
    • Urayasu, Chiba, Japan, 2790021
      • Recruiting
      • Juntendo University Urayasu Hospital
      • Contact: Hitoshi Suzuki, PhD, MD; Phone Number: +81473533111; Email: shitoshi@juntendo.ac.jp
  • Fukuoka
    • Kurume, Fukuoka, Japan, 8300011
      • Recruiting
      • Kurume University Hospial
      • Contact: Kei Fukami, PhD, MD; Phone Number: +81942317002; Email: fukami@kurume-u.ac.jp
      • Contact: Yusuke Kaida, PhD, MD; Phone Number: +81942317002; Email: kaida_yuusuke@kurume-u.ac.jp
  • Hokkaido
    • Asahikawa, Hokkaido, Japan, 0788510
      • Recruiting
      • Asahikawa Medical University Hospital
      • Contact: Naoki Nakagawa, PhD, MD; Phone Number: +81166682442; Email: naka-nao@asahikawa-med.ac.jp
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 9208641
      • Recruiting
      • Kanazawa University Hospital
      • Contact: Yasunori Iwata, PhD, MD; Phone Number: +81762652499; Email: iwatay@staff.kanazawa-u.ac.jp
  • Mie
    • Tsu, Mie, Japan, 5148507
      • Recruiting
      • Mie University Hospial
      • Contact: Tomoko Sugiura; Phone Number: +81592315403; Email: renal@med.mie-u.ac.jp
      • Contact: Kan Katayama, PhD, MD; Phone Number: +81592321111; Email: katayamk@med.mie-u.ac.jp
  • Miyagi
    • Sendai, Miyagi, Japan, 9808574
      • Recruiting
      • Tohoku University Hospital
      • Contact: Tasuku Nagasawa, PhD, MD; Phone Number: +81227177000
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 4313129
      • Recruiting
      • Hamamatsu University Hosptial
      • Contact: Hideo Yasuda, PhD, MD; Phone Number: +81534352261; Email: ysdh@hama-med.ac.jp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Rituximab group in double-blind phase	Drug: Rituximab (genetical recombination); Administer 1,000 mg of rituximab (genetical recombination) IV infusion every two weeks for two doses in double-blind phase.; Drug: 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.
Placebo Comparator: Placebo group in double-blind phase	Drug: Placebo; Administer placebo IV infusion every two weeks for two doses in double-blind phase.
Other: Rituximab group in open-label phase	Drug: Rituximab (genetical recombination); Administer 1,000 mg of rituximab (genetical recombination) IV infusion every two weeks for two doses in double-blind phase.; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients achieving ICR I	Achieving ICR I is defined as "Urine protein-creatinine ratio < 1.0 g/gCr".	up to 26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients who are CR, ICR I, ICR II, NR or PR	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	up to 26 weeks
Duration before achieving CR, ICR I, ICR II or PR	Duration of achieving CR, ICR I, ICR II or PR is summarized.	up to 26 weeks
Urine protein-creatinine ratio	The differences of urine protein-creatinine ratio between prior to treatment and at each timepoint are summarized.	up to 26 weeks
eGFR	The differences of eGFR between prior to treatment and at each timepoint are summarized.	up to 26 weeks
B-cells (CD19-positive and CD20-positive cells)	B cell counts (CD19 positive and CD20 positive cell counts) at each timepoint are summarized.	up to 26 weeks
Expression of HACA	The number of patients expressing HACA, and the proportion of these patients at each timepoint are summarized.	up to 26 weeks
Serum rituximab (genetical recombination) concentration	Serum rituximab (genetical recombination) level at each timepoint are summarized.	up to 26 weeks

Collaborators and Investigators

• Sponsor: Shoichi Maruyama MD PhD
• Investigators: Principal Investigator: Shoichi Shoichi, PhD, MD, Nagoya University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: June 13, 2023
• First Submitted That Met QC Criteria: June 13, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 9, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Disease; Nephritis; Syndrome; Glomerulonephritis; Nephrotic Syndrome; Nephrosis; Glomerulonephritis, Membranous; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Rituximab
• Other Study ID Numbers: CAMCR-020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: If the principal investigator, clinical trial office, main stakeholder conclude that secondary use of individual data obtained in this clinical trial is beneficial for additional analysis, the secondary use of data excluding personal information will be acceptable after publication of results.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No