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

Phase 2

Completed

• Conditions: Primary IgA Nephropathy
• Interventions: Biological: placebo; Biological: RC18 160mg; Biological: RC18 240mg

• Registration Number: NCT04291781
• Lead Sponsor: RemeGen Co., Ltd.

Brief Summary

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.

Detailed Description

Both RC18 and Recombinant Human B Lymphocyte Stimulator Receptor-Antibody Fusion Protein for Injection are other names of Tai Ai.

After a 35-day screen period, subjects are randomly allocated into 3 groups receiving subcutaneous injection of Tai Ai 160mg, Tai Ai 240mg, and placebo once a week individually. The treatment lasts 24 weeks. Subjects, the sponsor, investigators are blinded in the whole process of the trial.

Study Timeline

• Study First Submitted: 2020-02-27
• Study First Submitted QC: 2020-02-28
• Study First Posted: 2020-03-02
• Study Start: 2020-04-13
• Primary Completion: 2021-05-20
• Study Completion: 2021-05-20
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-16
• Last Update Posted: 2021-07-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

1. Signing the informed consent;
2. Biopsy confirmed diagnosis of IgA nephropathy;
3. Male or female, between 18 and 70 years age;
4. Before randomization, 24-hour urine protein excretion of ≥1g/24h in every screening visit;
5. Estimated glomerular filtration rate (eGFR) (CKD-EPI formula) of >45 ml/min per 1.73m2;
6. 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

1. 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

2. 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.;

3. 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.

4. 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;

5. Treating with systemic corticosteroids drug(excluding topical or nasal steroids) within 6 months prior to randomizing;

6. Treating with systemic immunosuppressor within 6 months prior to randomizing: cyclophosphamide, azathioprine, mycophenolate mofetil, leflunomide, tacrolimus, cyclosporine, rituximab, tripterygium wilfordii, etc.;

7. Requiring hospitalization or intravenous antibiotics treatment due to active infection within 6 months prior to randomizing;

8. Active tuberculosis or latent carrier;

9. Positive in herpes zoster, HIV antibody or HCV antibody;

10. 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.)

11. With malignant tumors;

12. Pregnancy or lactation, or patients with family planning during the experiment;

13. Inevitably administrate nephrotoxic drugs during the study period;

14. Allergy to human biological products;

15. Receiving any other experimental drug 4 weeks or 5 times half-life of the experimental drug (up to the longer time) prior to randomizing;

16. Not suitable for the study judged by investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	Placebo S.C. once weekly ,and a total of 24 doses
RC18 160mg	RC18 160mg	RC18 160mg subcutaneous injection (S.C.) once weekly ,and a total of 24 doses
RC18 240mg	RC18 240mg	RC18 240mg S.C. once weekly ,and a total of 24 doses

Primary Outcome Measures

Name	Time	Method
Change from baseline in 24-hour urine protein excretion at Week 24;	week 24	based on the 24 -hour urine collection

Secondary Outcome Measures

Name	Time	Method
Change from baseline in estimated Glomerular Filtration Rate(eGFR)	week 0, 4, 8, 12, 16, 20, 24	eGFR is calculated using the CKD-EPI method.
Change from baseline in urine protein/creatine ratio(UPCR) and/or urine albumin/ creatine ratio(UACR)	week 0, 4, 8, 12, 16, 20, 24
Change from baseline in Immunoglobulin G(IgG);	week 0, 4, 8, 12, 16, 20, 24
Change from baseline in Immunoglobulin M(IgM);	week 0, 4, 8, 12, 16, 20, 24
Change from baseline in Immunoglobulin A(IgA);	week 0, 4, 8, 12, 16, 20, 24
Change from baseline in the count of urine red blood cells	week 0, 4, 8, 12, 16, 20, 24
Change from baseline in the count of B-lymphocytes (CD19+)	week 0, 4, 8, 12, 16, 20, 24
Change from baseline in complement 3（C3）	week 0, 4, 8, 12, 16, 20, 24
Change from baseline in complement 4 (C4)	week 0, 4, 8, 12, 16, 20, 24
The incidence rate and severity of adverse events.	week 0, 4, 8, 12, 16, 20, 24	An adverse event is any undesirable experience associated with the use of a medical product in a patient.

Trial Locations

Locations (1)

Peking University First Hospital.; 🇨🇳 Beijing, Beijing, China