Clinical trial NCT05668403: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Primary Membranous Nephropathy
Lead sponsor: Shanghai Jiaolian Drug Research and Development Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: Shanghai Pharmaceuticals Holding Co., Ltd
First posted: 2022-12-29
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Dose limiting toxicity（DLT）
timeFrame: Approximately 1 years
measure: Security: Incidence of Treatment-Emergent Adverse Events
timeFrame: Approximately 2 years
Secondary outcomes:
measure: PK (Pharmacokinetics)
timeFrame: Approximately 1 years
measure: PK (Pharmacokinetics)
timeFrame: Approximately 1 years
measure: PK (Pharmacokinetics)
timeFrame: Approximately 1 years
measure: Biomarkers
timeFrame: Approximately 1 years
measure: Immunogenicity
timeFrame: Approximately 1 years
measure: Dynamics of pharmacodynamics
timeFrame: Approximately 1 years
measure: Proportion of subjects achieving clinical remission
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Shijiazhuang
country: China
facility: Hebei General Hospital
state: Hebei
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Hangzhou
country: China
facility: The First Affiliated Hospital,College of Medicine,Zhejiang University
state: Zhejiang
city: Beijing
country: China
facility: Peking university first hospital
city: Shanghai
country: China
facility: Longhua Hospital Shanghai University of Traditional Chinese Medicine
city: Shanghai
country: China
facility: Longhua Hospital Shanghai University of Traditional Chinese Medicine
Study officials:
References: