A Study of RC18 Administered Subcutaneously to Subjects With IgA(Immunoglobulin A) Nephropathy

Study Overview
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Brief Summary
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To evaluate the safety and efficacy of Tai Ai (Recombinant Human B Lymphocyte Stimulator Receptor-Antibody Fusion Protein for Injection) in the treatment of IgA nephropathy.

Official Title
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Phase II Clinical Trial of RC18(Recombinant Human B Lymphocyte Stimulator Receptor - Antibody Fusion Protein for Injection) in the Treatment of IgA Nephropathy

Conditions
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IgA Nephropathy

Intervention / Treatment
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* Biological: RC18 160mg
* Biological: RC18 240mg
* Biological: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signing the informed consent; Biopsy confirmed diagnosis of IgA nephropathy; Male or female, between 18 and 70 years age; Before randomization, 24-hour urine protein excretion of ≥1g/24h in every screening visit; Estimated glomerular filtration rate (eGFR) (CKD-EPI formula) of >45 ml/min per 1.73m2; Have received the ACEI(Angiotension converting enzyme inhibitors)/ARB(Angiotensin receptor blocker) standard treatment for 24 weeks prior to randomization, and have stabled the dosage (within the maximum tolerated dosage) for 4 weeks prior to randomization. Exclusion Criteria: Significant abnormalities in clinical laboratory values (including, but not limited to, the following indicators)： Items Abnormal value WBC(white blood cell count) <3*10^9/L PMN(Neutrophil count) <1.5*10^9/L HGB(hemoglobin) <85g/L PLT(blood platelet count) <80*10^9/L TBil(total bilirubin) >1.5*ULN ALT(Alanine aminotransferase) >3*ULN AST( Aspartate transaminase) >3*ULN ALP(alkaline phosphatase) >2*ULN CK(creatine kinase) >5*ULN Any secondary IgA nephropathy caused by Henoch-Schönlein purpura, ankylosing spondylitis, systemic lupus erythematosus, sjogren syndrome, viral hepatitis, liver cirrhosis, rheumatoid arthritis, mixed connective tissue disease, polyarteritis nodosa, erythema nodosum, psoriasis, ulcerative colitis, crohn's disease, tumor, AIDS ,etc.; Any nephropathy with special pathologic or clinical types, such as nephrotic syndrome, crescentic glomerulonephritis(with >50% of biopsied glomeruli), IgA nephropathy with minimal change disease (MCD-IgAN); and IgA nephropathy requiring corticosteroids treatment. Suffering from cardiovascular and cerebrovascular events (myocardial infarction, unstable angina, ventricular arrhythmia, New York heart association grade III-IV heart failure, stroke, etc.) within the last 12 weeks; Treating with systemic corticosteroids drug(excluding topical or nasal steroids) within 6 months prior to randomizing; Treating with systemic immunosuppressor within 6 months prior to randomizing: cyclophosphamide, azathioprine, mycophenolate mofetil, leflunomide, tacrolimus, cyclosporine, rituximab, tripterygium wilfordii, etc.; Requiring hospitalization or intravenous antibiotics treatment due to active infection within 6 months prior to randomizing; Active tuberculosis or latent carrier; Positive in herpes zoster, HIV antibody or HCV antibody; Active hepatitis or severe liver disease, and HBV infection (According to the HBV screening test, ①excluded the HBsAg-positive; ②HBsAg-negative and HBcAb-positive, the HBV-DNA should be tested to determine the situation: the HBV-DNA positive subjects should be excluded, while the HBV-DNA negative subjects can participated in.) With malignant tumors; Pregnancy or lactation, or patients with family planning during the experiment; Inevitably administrate nephrotoxic drugs during the study period; Allergy to human biological products; Receiving any other experimental drug 4 weeks or 5 times half-life of the experimental drug (up to the longer time) prior to randomizing; Not suitable for the study judged by investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RC18 160mg<br>RC18 160mg SC once weekly ,and total of 24 doses | Biological: RC18 160mg<br>* subcutaneous injection RC18 160mg on the upper arm, abdomen, or upper thigh outside;<br>|
| Experimental: RC18 240mg<br>RC18 240mg SC once weekly ,and total of 24 doses | Biological: RC18 240mg<br>* subcutaneous injection RC18 240mg on the upper arm, abdomen, or upper thigh outside;<br>|
| Placebo Comparator: Placebo<br>Placebo SC once weekly ,and total of 24 doses | Biological: placebo<br>* subcutaneous injection placebo on the upper arm, abdomen, or upper thigh outside;<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in 24-hour urine protein excretion level at Week 24; | 24-hour urine protein measures the amount of protein released in urine over a 24-hour period. | week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in eGFR | eGFR=Estimated Glomerular Filtration Rate | week 0、4、8、12、16、20、24 | 
| Change from baseline in urine protein/creatine ratio(UPCR) and/or urine albumin/ creatine ratio(UACR) | Each center tested for UPCR and / or UACR needs to be as consistent as possible. | week 0、4、8、12、16、20、24 | 
| Change from baseline in the count of urine red blood cells | The method of measuring the urine red blood cells in each center needs to be as consistent as possible. | week 0、4、8、12、16、20、24 | 
| Change from baseline in the values of Immunoglobulin G(IgG); | The content of IgG was detected by immunological index. | week 0、4、8、12、16、20、24 | 
| Change from baseline in the values of Immunoglobulin M(IgM); | The content of IgM was detected by immunological index. | week 0、4、8、12、16、20、24 | 
| Change from baseline in the values of Immunoglobulin A(IgA); | The content of IgG was detected by immunological index. | week 0、4、8、12、16、20、24 | 
| 1. Change from baseline in the values of B-lymphocyte (CD19+) | The content of B-lymphocyte was detected by immunological index. | week 0、4、8、12、16、20、24 | 
| 1. Change from baseline in the values of complement 3（C3） | The content of complement 3 was detected by immunological index. | week 0、4、8、12、16、20、24 | 
| 1. Change from baseline in the values of complement 4 (C4) | The content of complement 4 was detected by immunological index. | week 0、4、8、12、16、20、24 | 
| The incidence rate and severity of adverse events. | To evaluate the safety of multiple intravitreal injection of each group. | week 0、4、8、12、16、20、24 |