A Phase I Clinical Study of Recombinant Humanized Anti-CD20(B-lymphocyte Antigen CD20) Monoclonal Antibody Subcutaneous Injection in the Treatment of Primary Membranous Nephropathy

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profiles and Preliminary Efficacy of Subcutaneous Injection of Recombinant Humanized Anti-CD20 Monoclonal Antibody in the Treatment of Primary Membranous Nephropathy

This Phase I Clinical Study assessed the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profiles and Preliminary Efficacy of Subcutaneous Injection of Recombinant Humanized Anti-CD20 Monoclonal Antibody in the Treatment of Primary Membranous Nephropathy

Study Overview

• Status: Recruiting
• Conditions: Primary Membranous Nephropathy
• Intervention / Treatment: Drug: B007

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Minghui Zhao; Phone Number: 0086-13501243815; Email: mhzhao@bjmu.edu.cn

Study Locations

• China
  • Beijing, China, 100010
    • Recruiting
    • Peking University First Hospital
    • Contact: Minghui Zhao; Phone Number: 0086-13501243815; Email: mhzhao@bjmu.edu.cn
  • Shanghai, China, 200032
    • Recruiting
    • Longhua Hospital Shanghai University of Traditional Chinese Medicine
    • Contact: Yueyi Deng; Phone Number: 0086-021-64385700; Email: lhgcpoffice@126.com
  • He'nan
    • Zhengzhou, He'nan, China, 410100
      • Recruiting
      • The First Affiliated Hospital of Zhengzhou University
      • Contact: Zhangsuo Liu; Phone Number: 0086-0371-66913114; Email: 66862001@163.com
  • Hebei
    • Shijiazhuang, Hebei, China, 050057
      • Recruiting
      • Hebei General Hospital
      • Contact: Kai Niu; Phone Number: 0086-0311-85989696; Email: hbpphosp@126.com
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • the First Affiliated Hospital,College of Medicine,Zhejiang University
      • Contact: Heng Li; Phone Number: 0086-0571-87236114; Email: zdyy6616@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects who have fully understood this study and voluntarily signed the informed consent form;
2. Male or female subjects, aged between 18 and 75 years;
3. Subjects with primary membranous nephropathy pathologically confirmed by renal biopsy;
4. Subjects with systolic blood pressure ≤ 140 mmHg and diastolic blood pressure ≤ 90 mmHg at screening;
5. If taking ACEI(Angiotensin converting enzyme inhibitors), ARB(Angiotensin receptor blocker), a stable dose within 4 weeks before screening is required;
6. Subjects who are able to follow the study protocol as judged by the investigator.

Exclusion Criteria:

1. Subjects with secondary membranous nephropathy;
2. Subjects with uncontrolled blood pressure as judged by the investigator within 3 months before screening;
3. Subjects with decreases in urine protein ≥ 50% within 6 months before screening;
4. Subjects who have received or are receiving renal replacement therapy;
5. Subjects with type 1 diabetes mellitus, or those with type 2 diabetes mellitus who are diagnosed as diabetic nephropathy by percutaneous renal biopsy;
6. Subjects who have a clear history of tuberculosis or have received anti-tuberculosis treatment;
7. Subjects with active bacterial, viral, fungal, mycobacterial, parasitic or other infections requiring systemic antibiotics or antiviral therapy;
8. Subjects with known history of severe allergic reactions to humanized monoclonal antibodies；
9. Subjects who received live vaccination, major surgery, or participated in other clinical trials within 28 days before receiving the study drug;
10. Pregnant or lactating women; women of childbearing potential who have not been sterilized do not agree to use appropriate contraceptive measures during treatment and for at least 12 months after the last dose of the study drug;
11. Subjects with serious, progressive, or uncontrolled disease that may increase risks during the participation in the study as assessed by the investigator;
12. Subjects with a history of alcoholism or drug abuse within 12 months;
13. Subjects with positive hepatitis B surface antigen; those with positive hepatitis C virus antibody; those with a history of immunodeficiency;
14. Subjects with CD4+ T lymphocyte count < 300 cells/μL;
15. Other conditions unsuitable for participation in this study determined by the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: B007:350mg; B007:350mg Subcutaneous injection was administered on days 1 and 15 B007 matched Placebo Subcutaneous injection was administered on days 1 and 15	Drug: B007; Drug: B007 injection Drug: Placebo injection
Experimental: B007:700mg; B007: 700mg Subcutaneous injection was administered on days 1 and 15 B007 matched Placebo Subcutaneous injection was administered on days 1 and 15	Drug: B007; Drug: B007 injection Drug: Placebo injection
Experimental: B007:1000mg; B007: 1000mg Subcutaneous injection was administered on days 1 and 15 B007 matched Placebo Subcutaneous injection was administered on days 1 and 15	Drug: B007; Drug: B007 injection Drug: Placebo injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity（DLT）	Adverse reactions that are certainly or possibly related to the drug being tested during the dose escalation phase.	Approximately 1 years
Security: Incidence of Treatment-Emergent Adverse Events	Adverse event type, incidence, duration, correlation with study drug	Approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK (Pharmacokinetics)	Cmax	Approximately 1 years
PK (Pharmacokinetics)	Tmax	Approximately 1 years
PK (Pharmacokinetics)	AUC0-last（Area Under Curve of 0-last）	Approximately 1 years
Biomarkers	Changes in serum anti-PLA2R(Antiphospholipase A2 receptor) antibody levels relative to baseline	Approximately 1 years
Immunogenicity	Incidence of ADA(Adenosine deaminase)	Approximately 1 years
Dynamics of pharmacodynamics	Changes of peripheral blood CD19+B cells(B-lymphocyte antigen CD19) relative to baseline	Approximately 1 years
Proportion of subjects achieving clinical remission	Proportion of subjects achieving clinical remission	Approximately 2 years

Collaborators and Investigators

• Sponsor: Shanghai Jiaolian Drug Research and Development Co., Ltd
• Collaborators: Shanghai Pharmaceuticals Holding Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: December 12, 2022
• First Submitted That Met QC Criteria: December 20, 2022
• First Posted (Actual): December 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Kidney Diseases; Glomerulonephritis, Membranous
• Other Study ID Numbers: B007-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No