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

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

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.

Study Overview

• Status: Completed
• Conditions: Primary IgA Nephropathy
• Intervention / Treatment: Biological: RC18 160mg; Biological: RC18 240mg; Biological: placebo

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 Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100010
      • Peking University First Hospital.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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. During screening, 24-hour urine protein excretion ≥0.75 g/24h at Visit 1 and/or Visit 2 and at Visit 3;
5. Estimated glomerular filtration rate (eGFR) (CKD-EPI ) >35 ml/min per 1.73m^2;
6. Have received the Angiotension converting enzyme Inhibitors(ACEI)/Angiotensin receptor blocker(ARB) standard treatment for 12 weeks prior to randomization, and have stabled the dosage (within the maximum tolerated dosage) for 4 weeks prior to randomization.

Exclusion Criteria:

1. Abnormal laboratory tests;
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), minimal change disease with IgA deposition; 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 3 months prior to randomizing;
6. Treating with systemic immunosuppressor within 3 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 3 months prior to randomizing;
8. Active tuberculosis or latent carrier without treatment;
9. Herpes zoster infected patients or patients with positive HIV antibody or positive HCV antibody;
10. Active hepatitis or severe liver disease, and HBV infection (According to the HBV screening test, ① 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 ，lactation, or patients with childbearing plans during the trial;
13. Nephrotoxic drugs is unavoidable during the study period;
14. Allergy to human-derived biologics;
15. Receiving any other investigating drug 4 weeks or 5 times half-life of the experimental drug (whichever is longer) prior to randomization;
16. Not suitable for the study judged by investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RC18 160mg; RC18 160mg subcutaneous injection (S.C.) once weekly ,and a total of 24 doses	Biological: RC18 160mg; subcutaneous injection on the upper arm, abdomen, or upper thigh outside; Other Names: Tai Ai, Recombinant Human B-Lymphocyte Stimulator Receptor- Antibody Fusion Protein
Experimental: RC18 240mg; RC18 240mg S.C. once weekly ,and a total of 24 doses	Biological: RC18 240mg; subcutaneous injection on the upper arm, abdomen, or upper thigh outside; Other Names: Tai Ai, Recombinant Human B-Lymphocyte Stimulator Receptor- Antibody Fusion Protein
Placebo Comparator: Placebo; Placebo S.C. once weekly ,and a total of 24 doses	Biological: placebo; subcutaneous injection on the upper arm, abdomen, or upper thigh outside;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in 24-hour urine protein excretion at Week 24;	based on the 24 -hour urine collection	week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in estimated Glomerular Filtration Rate(eGFR)	eGFR is calculated using the CKD-EPI method.	week 0, 4, 8, 12, 16, 20, 24
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.	An adverse event is any undesirable experience associated with the use of a medical product in a patient.	week 0, 4, 8, 12, 16, 20, 24

Collaborators and Investigators

• Sponsor: RemeGen Co., Ltd.
• Investigators: Principal Investigator: Hong Zhang, M.D., Peking University First Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2020
• Primary Completion (Actual): May 20, 2021
• Study Completion (Actual): May 20, 2021

Study Registration Dates

• First Submitted: February 27, 2020
• First Submitted That Met QC Criteria: February 28, 2020
• First Posted (Actual): March 2, 2020

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 13, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Glomerulonephritis, IGA; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins
• Other Study ID Numbers: 18C014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No