Effect of Zigakibart on Histologic, Circulating, and Excreted Markers of Kidney Disease and Dysfunction in Adults with IgA Nephropathy: An Open-Label Study

The primary objective is to evaluate whether zigakibart treatment alters the disease course in adults with IgA nephropathy. 5

Secondary objectives include:

• Assessment of safety and tolerability. 4
• Evaluation of the impact of the treatment on kidney tissue, renal function, and overall disease status. 5
• Investigation of the pharmacokinetics of the study drug. 6
• Analysis of the immunogenicity of the treatment. 10

This clinical trial involves 17 participants diagnosed with IgA nephropathy. The study population consists of adults, including both males and females, within the specified age ranges. Eligible subjects must weigh at least 45 kg with a body mass index no greater than 35.0 kg/m2. Inclusion requires a diagnosis of the condition within the previous 5 years and moderate kidney function, defined as an estimated glomerular filtration rate ≥45 mL/min/1.73 m². Additionally, participants must exhibit persistent proteinuria, characterized by total urine protein ≥0.5 g/day or a urine protein-creatinine ratio ≥0.5 g/g despite supportive therapy. For those diagnosed within the past 6 months, the threshold for proteinuria is total urine protein >1.5 g/day or a ratio >1.5 g/g.

This phase II, open-label, uncontrolled, multicenter study is designed to evaluate the efficacy of zigakibart in adults diagnosed with IgA nephropathy. Following an initial screening visit to confirm eligibility, participants will receive 600 mg of zigakibart via subcutaneous injection. The research methodology involves assessing changes in histologic, circulating, and excreted markers of kidney disease and dysfunction. The primary endpoint is the change in IgA deposition in kidney tissue after 1 or 2 years of treatment compared to baseline. Secondary endpoints include assessments of kidney function, such as estimated glomerular filtration rate and urine protein, as well as changes in the MEST-C score, inflammation markers, immunoglobulin levels, and zigakibart concentrations in the blood. Participant involvement is expected to last up to 2 years, with multiple follow-up assessments conducted throughout the treatment period to monitor clinical and laboratory parameters and adverse events.

The investigational medicinal product, zigakibart, is administered as a solution for injection. The dosage is 600 mg, delivered via subcutaneous injection.

The primary efficacy endpoint is the change in the level of IgA deposition in kidney tissue after 1 or 2 years of zigakibart treatment relative to baseline. Secondary assessments include kidney biopsy measures, specifically changes in the MEST-C score, CD68, and C3c after 1 or 2 years of treatment compared to baseline.

Efficacy is further evaluated through kidney function tests, including urine protein and estimated glomerular filtration rate, measured at multiple timepoints during the 2-year treatment period. Immunoglobulin levels, specifically IgA, IgM, and IgG, are monitored in the blood at multiple intervals. The impact on the immune response to vaccination is assessed between 6 and 23 months following the initial treatment. Additionally, zigakibart concentrations and the presence of antibodies against the study drug in the blood are measured at multiple timepoints throughout the 2-year duration.