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

Primary Membranous Nephropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05668403
• Other study ID #: B007-102
• Status: Recruiting
• Phase: Phase 1
• Start date: March 2, 2023
• Est. completion date: September 30, 2024

Study information

• Verified date: January 2024
• Source: Shanghai Jiaolian Drug Research and Development Co., Ltd
• Contact: Minghui Zhao
• Phone: 0086-13501243815
• Email: mhzhao[@]bjmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 52
• Est. completion date: September 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Glomerulonephritis, Membranous
• Kidney Diseases
• Primary Membranous Nephropathy

Intervention

Drug:
• B007
Drug: B007 injection Drug: Placebo injection
• B007
Drug: B007 injection Drug: Placebo injection
• B007
Drug: B007 injection Drug: Placebo injection

Locations

Country	Name	City	State
China	Peking university first hospital	Beijing
China	The First Affiliated Hospital,College of Medicine,Zhejiang University	Hangzhou	Zhejiang
China	Longhua Hospital Shanghai University of Traditional Chinese Medicine	Shanghai
China	Longhua Hospital Shanghai University of Traditional Chinese Medicine	Shanghai
China	Hebei General Hospital	Shijiazhuang	Hebei
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai Jiaolian Drug Research and Development Co., Ltd	Shanghai Pharmaceuticals Holding Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Security: Incidence of Treatment-Emergent Adverse Events	Adverse event type, incidence, duration, correlation with study drug	Approximately 2 years
Secondary	PK (Pharmacokinetics)	Cmax	Approximately 1 years
Secondary	PK (Pharmacokinetics)	Tmax	Approximately 1 years
Secondary	PK (Pharmacokinetics)	AUC0-last(Area Under Curve of 0-last)	Approximately 1 years
Secondary	Biomarkers	Changes in serum anti-PLA2R(Antiphospholipase A2 receptor) antibody levels relative to baseline	Approximately 1 years
Secondary	Immunogenicity	Incidence of ADA(Adenosine deaminase)	Approximately 1 years
Secondary	Dynamics of pharmacodynamics	Changes of peripheral blood CD19+B cells(B-lymphocyte antigen CD19) relative to baseline	Approximately 1 years
Secondary	Proportion of subjects achieving clinical remission	Proportion of subjects achieving clinical remission	Approximately 2 years