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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 Purpose

Primary Membranous Nephropathy

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
B007
B007
B007
Sponsored by
Shanghai Jiaolian Drug Research and Development Co., Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Membranous Nephropathy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Subjects who have fully understood this study and voluntarily signed the informed consent form; Male or female subjects, aged between 18 and 75 years; Subjects with primary membranous nephropathy pathologically confirmed by renal biopsy; Subjects with systolic blood pressure ≤ 140 mmHg and diastolic blood pressure ≤ 90 mmHg at screening; 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; If taking ACEI(Angiotensin converting enzyme inhibitors), ARB(Angiotensin receptor blocker), a stable dose within 8 weeks before screening is required; Subjects who are able to follow the study protocol as judged by the investigator. Exclusion Criteria: Subjects with secondary membranous nephropathy; Subjects with uncontrolled blood pressure as judged by the investigator within 3 months before screening; Subjects with decreases in urine protein ≥ 50% within 6 months before screening; Subjects who have received or are receiving renal replacement therapy; Subjects with type 1 diabetes mellitus, or those with type 2 diabetes mellitus who are diagnosed as diabetic nephropathy by percutaneous renal biopsy; Subjects who have a clear history of tuberculosis or have received anti-tuberculosis treatment; Subjects with active bacterial, viral, fungal, mycobacterial, parasitic or other infections requiring systemic antibiotics or antiviral therapy; Subjects with known history of severe allergic reactions to humanized monoclonal antibodies; Subjects who received live vaccination, major surgery, or participated in other clinical trials within 28 days before receiving the study drug; 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; Subjects with serious, progressive, or uncontrolled disease that may increase risks during the participation in the study as assessed by the investigator; Subjects with a history of alcoholism or drug abuse within 12 months; 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; Subjects with CD4+ T lymphocyte count < 300 cells/μL; Other conditions unsuitable for participation in this study determined by the Investigator.

Sites / Locations

  • Hebei General HospitalRecruiting
  • The First Affiliated Hospital of Zhengzhou UniversityRecruiting
  • The First Affiliated Hospital,College of Medicine,Zhejiang UniversityRecruiting
  • Peking university first hospitalRecruiting
  • Longhua Hospital Shanghai University of Traditional Chinese MedicineRecruiting
  • Longhua Hospital Shanghai University of Traditional Chinese MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

B007:350mg

B007:700mg

B007:1000mg

Arm Description

B007:350mg Subcutaneous injection was administered on days 1 and 15 B007 matched Placebo Subcutaneous injection was administered on days 1 and 15

B007: 700mg Subcutaneous injection was administered on days 1 and 15 B007 matched Placebo Subcutaneous injection was administered on days 1 and 15

B007: 1000mg Subcutaneous injection was administered on days 1 and 15 B007 matched Placebo Subcutaneous injection was administered on days 1 and 15

Outcomes

Primary Outcome Measures

Dose limiting toxicity(DLT)
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
Adverse event type, incidence, duration, correlation with study drug

Secondary Outcome Measures

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

Full Information

First Posted
December 12, 2022
Last Updated
May 31, 2023
Sponsor
Shanghai Jiaolian Drug Research and Development Co., Ltd
Collaborators
Shanghai Pharmaceuticals Holding Co., Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05668403
Brief Title
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

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 2, 2023 (Actual)
Primary Completion Date
March 31, 2024 (Anticipated)
Study Completion Date
September 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Jiaolian Drug Research and Development Co., Ltd
Collaborators
Shanghai Pharmaceuticals Holding Co., Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Membranous Nephropathy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
52 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
B007:350mg
Arm Type
Experimental
Arm Description
B007:350mg Subcutaneous injection was administered on days 1 and 15 B007 matched Placebo Subcutaneous injection was administered on days 1 and 15
Arm Title
B007:700mg
Arm Type
Experimental
Arm Description
B007: 700mg Subcutaneous injection was administered on days 1 and 15 B007 matched Placebo Subcutaneous injection was administered on days 1 and 15
Arm Title
B007:1000mg
Arm Type
Experimental
Arm Description
B007: 1000mg Subcutaneous injection was administered on days 1 and 15 B007 matched Placebo Subcutaneous injection was administered on days 1 and 15
Intervention Type
Drug
Intervention Name(s)
B007
Intervention Description
Drug: B007 injection Drug: Placebo injection
Intervention Type
Drug
Intervention Name(s)
B007
Intervention Description
Drug: B007 injection Drug: Placebo injection
Intervention Type
Drug
Intervention Name(s)
B007
Intervention Description
Drug: B007 injection Drug: Placebo injection
Primary Outcome Measure Information:
Title
Dose limiting toxicity(DLT)
Description
Adverse reactions that are certainly or possibly related to the drug being tested during the dose escalation phase.
Time Frame
Approximately 1 years
Title
Security: Incidence of Treatment-Emergent Adverse Events
Description
Adverse event type, incidence, duration, correlation with study drug
Time Frame
Approximately 2 years
Secondary Outcome Measure Information:
Title
PK (Pharmacokinetics)
Description
Cmax
Time Frame
Approximately 1 years
Title
PK (Pharmacokinetics)
Description
Tmax
Time Frame
Approximately 1 years
Title
PK (Pharmacokinetics)
Description
AUC0-last(Area Under Curve of 0-last)
Time Frame
Approximately 1 years
Title
Biomarkers
Description
Changes in serum anti-PLA2R(Antiphospholipase A2 receptor) antibody levels relative to baseline
Time Frame
Approximately 1 years
Title
Immunogenicity
Description
Incidence of ADA(Adenosine deaminase)
Time Frame
Approximately 1 years
Title
Dynamics of pharmacodynamics
Description
Changes of peripheral blood CD19+B cells(B-lymphocyte antigen CD19) relative to baseline
Time Frame
Approximately 1 years
Title
Proportion of subjects achieving clinical remission
Description
Proportion of subjects achieving clinical remission
Time Frame
Approximately 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects who have fully understood this study and voluntarily signed the informed consent form; Male or female subjects, aged between 18 and 75 years; Subjects with primary membranous nephropathy pathologically confirmed by renal biopsy; Subjects with systolic blood pressure ≤ 140 mmHg and diastolic blood pressure ≤ 90 mmHg at screening; 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; If taking ACEI(Angiotensin converting enzyme inhibitors), ARB(Angiotensin receptor blocker), a stable dose within 8 weeks before screening is required; Subjects who are able to follow the study protocol as judged by the investigator. Exclusion Criteria: Subjects with secondary membranous nephropathy; Subjects with uncontrolled blood pressure as judged by the investigator within 3 months before screening; Subjects with decreases in urine protein ≥ 50% within 6 months before screening; Subjects who have received or are receiving renal replacement therapy; Subjects with type 1 diabetes mellitus, or those with type 2 diabetes mellitus who are diagnosed as diabetic nephropathy by percutaneous renal biopsy; Subjects who have a clear history of tuberculosis or have received anti-tuberculosis treatment; Subjects with active bacterial, viral, fungal, mycobacterial, parasitic or other infections requiring systemic antibiotics or antiviral therapy; Subjects with known history of severe allergic reactions to humanized monoclonal antibodies; Subjects who received live vaccination, major surgery, or participated in other clinical trials within 28 days before receiving the study drug; 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; Subjects with serious, progressive, or uncontrolled disease that may increase risks during the participation in the study as assessed by the investigator; Subjects with a history of alcoholism or drug abuse within 12 months; 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; Subjects with CD4+ T lymphocyte count < 300 cells/μL; Other conditions unsuitable for participation in this study determined by the Investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Minghui Zhao
Phone
0086-13501243815
Email
mhzhao@bjmu.edu.cn
Facility Information:
Facility Name
Hebei General Hospital
City
Shijiazhuang
State/Province
Hebei
ZIP/Postal Code
050057
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kai Niu
Phone
0086-0311-85989696
Email
hbpphosp@126.com
Facility Name
The First Affiliated Hospital of Zhengzhou University
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
410100
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhangsuo Liu
Phone
0086-0371-66913114
Email
66862001@163.com
Facility Name
The First Affiliated Hospital,College of Medicine,Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heng Li
Phone
0086-0571-87236114
Email
zdyy6616@126.com
Facility Name
Peking university first hospital
City
Beijing
ZIP/Postal Code
100010
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Minghui Zhao
Phone
0086-13501243815
Email
mhzhao@bjmu.edu.cn
Facility Name
Longhua Hospital Shanghai University of Traditional Chinese Medicine
City
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ming Yang
Phone
0086-021-64385700
Email
lhgcpoffice@126.com
Facility Name
Longhua Hospital Shanghai University of Traditional Chinese Medicine
City
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yueyi Deng
Phone
0086-021-64385700
Email
lhgcpoffice@126.com

12. IPD Sharing Statement

Learn more about this trial

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

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