Phase II Basket Trial of BI 764198 in Adults and Adolescents With Proteinuric Kidney Diseases

The primary objective is to estimate the mean relative change from baseline to Week 20 in 24-hour urinary protein-to-creatinine ratio in each cohort of proteinuric kidney diseases. This endpoint is clinically relevant because reduction in proteinuria is a key marker of disease activity and renal risk. Secondary objectives are to compare the proportion of participants achieving at least a 25% or 40% reduction in 24-hour urinary protein-to-creatinine ratio between treatment arms, and to estimate the between-arm difference in mean within-participant absolute change in estimated glomerular filtration rate based on cystatin C from baseline to Week 20 in each cohort. These outcomes further assess treatment effect on proteinuria response and kidney function.

The trial enrolled 83 participants with proteinuric kidney diseases, including male and female patients aged 18 years or older and adolescents aged 12 years or older for the TR-pMCD cohort. The study population was selected from participants with a body mass index of ≤40 kg/m2, a screening weight of at least 40 kg, estimated glomerular filtration rate of ≥25 mL/min/1.73 m2, and seated systolic blood pressure within the specified limits for age. Participants were required to be on stable background treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and some were also receiving stable doses of non-steroidal mineralocorticoid receptor antagonists, endothelin receptor antagonists, glucagon-like peptide-1 receptor agonists, SGLT2 inhibitors, or oral immunosuppressive therapy. Further inclusion criteria applied.

The study is a phase II, multicentre, randomized, 2-arm, parallel-group, double-blind, placebo-controlled basket trial evaluating BI 764198 versus matching placebo in four proteinuric kidney diseases. The trial is designed to assess safety, tolerability, pharmacokinetics, and efficacy, with the primary endpoint defined as the mean relative change from baseline to Week 20 in 24-hour urinary protein-to-creatinine ratio. Study participation begins with a screening visit, where eligibility is assessed and baseline criteria are confirmed. Eligible participants are then randomized to receive study treatment during the double-blind treatment period. Follow-up assessments are performed during the trial to monitor study outcomes and treatment response. The end-of-study visit occurs at Week 20, which marks the end of the randomized treatment period. The expected duration of participant involvement is up to 20 weeks. Early termination from the study may occur if a participant withdraws consent, no longer meets eligibility or safety requirements, or if discontinuation is judged necessary by the investigator.

The investigational treatment was BI 764198, supplied as a film-coated tabletoral use. The active substance was [4-(6-aminopyridazin-3-yl)piperidin-1-yl][5-(4-fluorophenoxy)-4-methoxypyridin-2-yl]methanone. The administered dose was 00 mg, with dosing given once daily as part of the study regimen. The trial also included a placebo matching BI 764198, presented as a comparator treatment. No additional details on dosing schedule modifications or compliance monitoring were provided in the source data.

Efficacy will be assessed by the mean relative change from baseline to Week 20 in 24-hr urinary protein-to-creatinine ratio (UPCR) measured in mg/g in each of the four glomerular disease cohorts. Additional efficacy assessments will include treatment response, defined as at least 25% relative reduction in 24-hr UPCR from baseline to Week 20, treatment response, defined as at least 40% relative reduction in 24-hr UPCR from baseline to Week 20, and absolute change in eGFR in mL/min/1.73m2 based on cystatin C from baseline to Week 20.