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
Study Details
Study Description
Brief 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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Dose limiting toxicity（DLT） [Approximately 1 years]
Adverse reactions that are certainly or possibly related to the drug being tested during the dose escalation phase.
- Security: Incidence of Treatment-Emergent Adverse Events [Approximately 2 years]
Adverse event type, incidence, duration, correlation with study drug
Secondary Outcome Measures
- PK (Pharmacokinetics) [Approximately 1 years]
Cmax
- PK (Pharmacokinetics) [Approximately 1 years]
Tmax
- PK (Pharmacokinetics) [Approximately 1 years]
AUC0-last（Area Under Curve of 0-last）
- Biomarkers [Approximately 1 years]
Changes in serum anti-PLA2R(Antiphospholipase A2 receptor) antibody levels relative to baseline
- Immunogenicity [Approximately 1 years]
Incidence of ADA(Adenosine deaminase)
- Dynamics of pharmacodynamics [Approximately 1 years]
Changes of peripheral blood CD19+B cells(B-lymphocyte antigen CD19) relative to baseline
- Proportion of subjects achieving clinical remission [Approximately 2 years]
Proportion of subjects achieving clinical remission
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subjects who have fully understood this study and voluntarily signed the informed consent form;
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Male or female subjects, aged between 18 and 75 years;
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Subjects with primary membranous nephropathy pathologically confirmed by renal biopsy;
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Subjects with systolic blood pressure ≤ 140 mmHg and diastolic blood pressure ≤ 90 mmHg at screening;
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Subjects with glomerular filtration rate ≥ 45 mL/min/1.73 m2 estimated by CKD-EPI equation(the Chronic Kidney Disease Epidemiology Collaboration equation), or endogenous creatinine clearance ≥ 45 mL/min based on 24-hour urine collection;
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If taking ACEI(Angiotensin converting enzyme inhibitors), ARB(Angiotensin receptor blocker), a stable dose within 8 weeks before screening is required;
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Subjects who are able to follow the study protocol as judged by the investigator.
Exclusion Criteria:
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Subjects with secondary membranous nephropathy;
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Subjects with uncontrolled blood pressure as judged by the investigator within 3 months before screening;
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Subjects with decreases in urine protein ≥ 50% within 6 months before screening;
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Subjects who have received or are receiving renal replacement therapy;
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Subjects with type 1 diabetes mellitus, or those with type 2 diabetes mellitus who are diagnosed as diabetic nephropathy by percutaneous renal biopsy;
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Subjects who have a clear history of tuberculosis or have received anti-tuberculosis treatment;
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Subjects with active bacterial, viral, fungal, mycobacterial, parasitic or other infections requiring systemic antibiotics or antiviral therapy;
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Subjects with known history of severe allergic reactions to humanized monoclonal antibodies；
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Subjects who received live vaccination, major surgery, or participated in other clinical trials within 28 days before receiving the study drug;
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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;
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Subjects with serious, progressive, or uncontrolled disease that may increase risks during the participation in the study as assessed by the investigator;
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Subjects with a history of alcoholism or drug abuse within 12 months;
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Subjects with positive hepatitis B surface antigen or HBV(hepatitisBvirus) DNA ≥ the upper limit of laboratory normal at screening; those with positive hepatitis C virus antibody or HCV(hepatitis C virus) RNA ≥ the upper limit of laboratory normal at screening; those with a history of immunodeficiency;
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Subjects with CD4+ T lymphocyte count < 300 cells/μL;
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Other conditions unsuitable for participation in this study determined by the Investigator.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peking university first hospital | Beijing | China | 100010 |
Sponsors and Collaborators
- Shanghai Jiaolian Drug Research and Development Co., Ltd
- Shanghai Pharmaceuticals Holding Co., Ltd
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- B007-102