Clinical trial NCT04291781: A Study of RC18 Administered Subcutaneously to Subjects With Primary IgA(Immunoglobulin A) Nephropathy
Official title: Phase II Clinical Trial of RC18(Recombinant Human B Lymphocyte Stimulator Receptor - Antibody Fusion Protein for Injection) in the Treatment of Primary IgA Nephropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary IgA Nephropathy
Lead sponsor: RemeGen Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-03-02
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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\&#39;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.

Primary outcomes:
measure: Change from baseline in 24-hour urine protein excretion at Week 24;
timeFrame: week 24
Secondary outcomes:
measure: Change from baseline in estimated Glomerular Filtration Rate(eGFR)
timeFrame: week 0, 4, 8, 12, 16, 20, 24
measure: Change from baseline in urine protein/creatine ratio(UPCR) and/or urine albumin/ creatine ratio(UACR)
timeFrame: week 0, 4, 8, 12, 16, 20, 24
measure: Change from baseline in Immunoglobulin G(IgG);
timeFrame: week 0, 4, 8, 12, 16, 20, 24
measure: Change from baseline in Immunoglobulin M(IgM);
timeFrame: week 0, 4, 8, 12, 16, 20, 24
measure: Change from baseline in Immunoglobulin A(IgA);
timeFrame: week 0, 4, 8, 12, 16, 20, 24
measure: Change from baseline in the count of urine red blood cells
timeFrame: week 0, 4, 8, 12, 16, 20, 24
measure: Change from baseline in the count of B-lymphocytes (CD19+)
timeFrame: week 0, 4, 8, 12, 16, 20, 24
measure: Change from baseline in complement 3（C3）
timeFrame: week 0, 4, 8, 12, 16, 20, 24
measure: Change from baseline in complement 4 (C4)
timeFrame: week 0, 4, 8, 12, 16, 20, 24
measure: The incidence rate and severity of adverse events.
timeFrame: week 0, 4, 8, 12, 16, 20, 24
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital.
state: Beijing
Study officials:
affiliation: Peking University First Hospital
name: Hong Zhang, M.D.
role: PRINCIPAL_INVESTIGATOR
References: