A Randomized, Controlled, Multicenter Phase II Clinical Study to Evaluate the Efficacy, Safety, and Tolerability of HLX79 (Human Sialidase Fusion Protein) in Combination With Rituximab Injection (HLX01, Anti-CD20 Antibody) Versus Placebo in Patients With Active Glomerulonephritis
The primary objectives of this clinical trial is to evaluate the safety and tolerability of HLX79 in combination with HLX01 versus placebo in combination with HLX01 in the treatment of glomerulonephritis. The secondary objective are to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of HLX79 and HLX01, the clinical efficacy, the dynamic changes of biomarkers of HLX79 in combination with HLX01 in the treatment of glomerulonephritis. The subjects will receive different doses of HLX79 (10, 20, or 30 mg/kg) or placebo, all in combination with HLX01. After the end of the first treatment period, subjects will enter a 20-week follow-up period and then undergo pre-second treatment period assessments. If the investigator determines that the subject does not require the second treatment period, the subject will continue in follow-up until completing the total 48-week follow-up period.
• Patients who voluntarily participate in this clinical study, fully understand and have been informed about the study, have signed the informed consent form (ICF), and are willing to follow and able to complete all study procedures.
• Male or female, aged 18-70 years (both inclusive) at the time of signing the ICF.
• Diagnosed with primary membranous nephropathy (MN) within 1 year prior to screening
• If a diagnosis of primary MN is confirmed, a renal biopsy pathological diagnosis prior to screening or a renal biopsy diagnosis obtained during screening should be available, or patients with nephrotic syndrome and a positive anti-PLA2R antibody test within 6 months prior to screening; secondary MN (secondary to infection, tumor, SLE, drugs, etc.) should be excluded; subjects should have received treatment with angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blocker (ARBs) at the highest tolerated dose judged by the investigator for 3 months prior to screening (unless intolerance to ACEI/ARB, contraindications to their use or a low blood pressure that could induce side effects, at the investigator's discretion) and also meet one of the following high-risk criteria:
‣ Urine protein \> 8 g/24 h at screening.
⁃ eGFR ≥ 60 mL/min/1.73 m2 and urine protein \> 3.5 g/24 h at screening, and must meet at least one of the following at screening:
• Anti-PLA2R antibody \> 50 relative units (RU)/mL;
∙ Serum albumin \< 25 g/L;
∙ Urine alpha 1 microglobulin \> 40 μg/min;
∙ Urine IgG \> 1 μg/min;
∙ Urine β2 microglobulin \> 250 mg/24 h;
∙ IgG clearance/albumin clearance \> 0.2.
• Women of childbearing potential (WOCBP) must undergo a pregnancy test at screening and obtain a negative result.
• WOCBP or male subjects must agree to take effective contraceptive measures starting from signing the ICF until 12 months after the last dose of the investigational medicinal product (IMP).