Table 3.

Objectives and related end points for the double-blind and open-label treatment periods

	Objectives	End points
Double-blind period
Primary objective	To demonstrate the superiority of iptacopan vs. placebo on reducing proteinuria at 6 months	Log-transformed ratio to baseline in UPCR (sampled from a 24-h urine collection) at 6 months
Secondary objectives	To demonstrate the superiority of iptacopan vs. placebo on improvement from baseline in eGFR at 6 months	Change from baseline in eGFR at 6 months
	To demonstrate the superiority of iptacopan vs. placebo in the proportion of patients who achieve a composite renal end point at 6 months	A participant meets the requirements of the composite renal end point if they satisfy the following criteria at the 6-month timepoint: (i) a stable or improved eGFR compared with baseline visit (≤15% reduction in eGFR) and (ii) a ≥50% reduction in UPCR compared with baseline visit
	To assess the effect of iptacopan vs. placebo on patient reported fatigue at 6 months	Change from baseline to 6 months in the FACIT-Fatigue score
	To assess the effect of iptacopan versus placebo on BP, HR, cardiac function, and biomarkers of cardiac injury in adolescents	Changes in HR, mean sitting DBP and msSBP, ECG parameters, and N-terminal pro-brain natriuretic peptide
	To evaluate the safety and tolerability of iptacopan vs. placebo during the 6-month double-blind period	Vital signs, ECGs, laboratory measurements, AEs, AESIs, and AE-related study drug discontinuation
Open-label period
Primary objective	To evaluate the effect of iptacopan on proteinuria at 12 months	Log-transformed ratio to baseline in UPCR at the 12-month visit (both study treatment arms) Log-transformed ratio to 6-month visit in UPCR at the 12-month visit in the placebo arm (iptacopan treatment period)
Secondary objectives	To evaluate the effect of iptacopan at 12 months on: •Improvement from baseline in eGFR •The proportion of patients who achieved a composite renal end point •Improvement of patient-reported fatigue	Change from baseline in eGFR at 12 months (both arms) and change in eGFR from 6 months to 12 months in the placebo arm (iptacopan treatment period) Proportion of patients who meet the criteria of achieving the composite renal end point at 12 months in both arms and from 6 months to 12 months in the placebo arm (iptacopan treatment period) Change from baseline in the FACIT-Fatigue score at 12 months in both arms and from 6 months to 12 months in the placebo arm (iptacopan treatment period)
	To assess the effect of iptacopan versus placebo on BP, HR, cardiac function, and biomarkers of cardiac injury in adolescents during the open-label period	Changes in HR, mean sitting DBP and msSBP, ECG parameters, and N-terminal pro-brain natriuretic peptide
	To evaluate the safety and tolerability of iptacopan during the open-label period as well as the whole treatment period	Vital signs, ECGs, laboratory measurements, AEs, AESIs, and AE-related study drug discontinuation

AEs, adverse events; AESIs, adverse events of special interest; BP, blood pressure; DBP, diastolic blood pressure; ECG, electrocardiogram; eGFR, estimated glomerular filtration rate; FACIT-Fatigue, functional assessment of chronic illness therapy-fatigue; HR, heart rate; msSBP, mean sitting systolic blood pressure; UPCR, urine protein–creatinine ratio.