Home > Nephrology > ERA 2024 > APPEAR-C3G: Iptacopan shows promise for Complement 3 Glomerulopathy

APPEAR-C3G: Iptacopan shows promise for Complement 3 Glomerulopathy

Presented by
Prof. David Kavanagh, Newcastle University, United Kingdom
Conference
ERA 2024
Trial
Phase 3, APPEAR-C3G
The APPEAR-C3G showed that the complement inhibitor iptacopan can improve proteinuria and delay the decline in eGFR in participants with complement 3 glomerulopathy (C3G).

Complement 3 glomerulopathy (C3G) is a rare renal disease characterised by the accumulation of C3 fragments in glomeruli, which in time can lead to end-stage kidney disease [1]. APPEAR-C3G (NCT04817618) trial is a randomised, double-blind, parallel-group, multicentre phase 3 trial of iptacopan versus placebo on top of supportive. Adults with biopsy-confirmed C3G, a urine protein-creatinine ratio ≥1.0 g/g and eGFR ≥30 mL/min/1.73 m2 were included. The initial treatment period consisted of 6 months of randomised iptacopan (38 participants) versus placebo (36 participants) treatment period, after which all participants received 6 months of iptacopan. The primary endpoint was 24-hour urine protein-creatinine ratio reduction after 6 months of therapy [2].

“The trial met its primary endpoint with a statistically significant and clinically meaningful reduction in proteinuria at 6 months”, said Prof. David Kavanagh (Newcastle University, United Kingdom). Overall, iptacopan led to a 30.2% reduction in 24-hour urine protein-creatinine ratio compared with a 7.6% increase seen with placebo after 6 months (mean 35.1% difference; P=0.0014). Iptacopan led to higher proportions of participants achieving both ≤15% degradation in eGFR and ≥50% reduction in urine protein-creatinine ratio (29.7% vs 5.6%; OR 7.145; 95% CI 1.429–35.723; P=0.0166). Furthermore, 6-month treatment with iptacopan reduced nephrotic-range proteinuria (31.6% vs 41.7%, iptacopan vs placebo) and led to a numerical improvement in eGFR scores. In total, 15.8% and 13.9% of participants had adverse events suspected to be related to iptacopan and placebo, respectively, while serious adverse events were reported in 5.3% and 2.8% of participants, respectively. However, there were no treatment discontinuations due to adverse events or deaths during the study.

“The study demonstrated a clinically significant and meaningful reduction on top of the standard-of-care with eGFR improvement”, said Prof. Kavanagh. “The safety profile was favourable in patients with C3G”.

  1. Schena FP, et al. Int J Mol Sci. 2020;21(2):525.
  2. Kavanagh D, et al. Efficacy and safety of iptacopan in patients with C3 glomerulopathy: results from the phase 3 APPEAR-C3G trial. Abstract #98, ERA 2024, 23–26 May, Stockholm, Sweden.

Medical writing support was provided by Mihai Surducan, PhD.

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