WCN25-1585 A Phase 1/2 Trial of Zigakibart in IgA Nephropathy (IgAN)

108 out of 119 (91%) eligible cohort participants were randomised and 29 (56%) consented to intervention (Figure 1).Baseline maternal data are presented inTable 1. Cohort recruitment rate was 0.86 participants /site /month.No serious adverse events (SAEs) were assessed to be intervention related (N36: 5 intervention, 31 standard care) but two standard care SAEs were considered life threatening due to preeclampsia; 48 fetal/neonatal AEs included one fetal death in standard care arm at 17 weeks after premature rupture of membranes, but no major congenital abnormalities were reported.Special interest AEs were hyperkalemia >6 mmol/L (2 cases, one per arm and standard care required treatment); symptomatic hypotension (0 cases).Pregnancy outcomes are presented inTable 2. Mean gestational age and live birth rates were high with no difference between intervention and standard care arms.There was a trend for higher mean birthweight and lower neonatal intensive care admission with intervention compared to standard care but the study was underpowered to detect differences in these outcomes.Two standard care and no intervention participants started haemodialysis before delivery.There were no differences in pre-pregnancy renal function compared to 6 weeks or 6 months post-partum.However, there was a trend to reduced creatinine concentration after delivery in participants with pre-pregnancy eGFR <45ml/min comparted to > 45ml/min in the intervention arm compared to standard care.(Figure 2)Conclusions: This is the first interventional RCT embedded in observational cohort of CKD pregnancy.Sites were able to successfully recruit and randomise participants in these high-risk pregnancies.There was no evidence of maternal or neonatal harm related to the intervention with signals of overall neonatal benefit associated with dietary nitrate supplementation and prevention of progression of kidney disease in those with advanced CKD.Evidence of efficacy is needed from a fully powered RCT.I have no potential conflict of interest to disclose.I did not use generative AI and AI-assisted technologies in the writing process.