The Selective Endothelin Receptor Antagonist SC0062 in IgA Nephropathy: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

IgA nephropathy (IgAN) in India is reported to have an onset at a younger age with faster progression to kidney failure requiring replacement therapy, where safe immunosuppression may improve the outcome. The gut-renal connection and multihit pathogenesis of IgAN targeted by an oral targeted-release formulation of budesonide available in the Western world showed that the molecule is safe and effective. In this study, we aimed to assess the safety and efficacy of oral controlled-release budesonide preparation in Indian patients with IgAN. We report a single-center open-label randomized controlled trial conducted in a tertiary care hospital in Eastern India, where adult patients with biopsy-proven IgAN with proteinuria > 1 g and estimated glomerular filtration rate (eGFR) > 45 mL/min/1.73 m2 were included after they had completed a run-in phase of 6 months with a maximized dose of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker. 53 patients were randomized to the control (26, only therapy angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, standard-of-care [SOC]) and intervention arms (27, 18 mg budesonide daily on top of SOC). The primary outcome was efficacy evaluation in terms of change in proteinuria and eGFR in the intervention arm; secondary outcomes mainly included treatment-emergent adverse events. All baseline parameters, including blood pressure, glycemic status, 24-hour urine protein levels, and eGFR, were comparable in both arms. At the end of 9 months, the mean 24-hour proteinuria was lower (P-value < 0.001) and the mean eGFR was significantly better (P-value < 0.001) in the intervention arm receiving budesonide plus SOC than in the control arm receiving only SOC. The total incidence of treatment-emergent adverse events was similar across both groups. Controlled-release budesonide may be considered an effective and safe disease-specific therapy in Indian patients with IgAN.

POS-045 Evaluating BCX9930, an Oral Factor D Inhibitor for Treatment of Complement-Mediated Kidney Disease: A Proof-of-Concept Study (RENEW)

Randomized Controlled Trial of Mycophenolate Mofetil in Children, Adolescents, and Adults With IgA Nephropathy

Background and Aims Most patients with IgA nephropathy (IgAN) will progress to kidney failure within 10-15 years of diagnosis. Sustained proteinuria is the best predictor of adverse long-term kidney outcomes and is a surrogate marker for efficacy. CD38+ plasma cells are likely the main source of pathogenic Gd-IgA1, and the related autoantibodies in IgAN. Felzartamab (felza; HIB202) is a recombinant purified human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that binds to CD38 on plasma cells and is being studied across immune-mediated kidney diseases such as IgAN, Primary Membranous Nephropathy, Lupus Nephritis, and Antibody Mediated Rejection. The primary aims of the IGNAZ study were to assess: 1) efficacy of felza compared to placebo on urine protein:creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) change from baseline, and 2) the relationship between exposure, safety, and efficacy in each of 3 dose groups vs. placebo. Interim results with 15 months of follow-up from this 24-month trial are presented. Method In Part 1, 48 IgAN subjects were randomized in a 1:1:1:1 ratio across a placebo and 3 active arms in this multicenter, double-blind placebo-controlled, phase IIa trial. The M1, M2, and M3 active arms received 2 doses in 15 days, 5 doses in 2 months, and 9 doses in 5 months, respectively. In Part 2, 6 Japanese subjects received the M3 regimen, open-label, and have been followed for 9 months. Key inclusion criteria included ages 18-80 years, biopsy confirmed diagnosis of IgAN within the past 8 years, proteinuria at screening ≥1.0 g/d, eGFR ≥30 ml/min/1.73 m2 (by CKD-EPI), and background stable and maximally tolerated renin angiotensin system inhibitors. Results 48 randomized subjects were enrolled at 28 sites in the US and in 14 different countries in Europe and in Asia, of which 46 completed the treatment phase. Mean (SD) baseline characteristics (Parts 1 and 2 combined): age 41.6 (12.3) yrs, UPCR 1.67 (1.0) g/g, eGFR 74.6 (30.3) ml/min/1.73 m2. 67% of subjects were male. Intention-to-treat with felza demonstrated rapid, clinically meaningful reductions in UPCR with the maximal treatment effect being observed in the M3 9-dose regimen. In Part 1, percentage change from baseline in UPCR was −14% for placebo and −25% for M3 9-dose arm at month 3, and +9% for placebo and −35% for M3 at month 6 (Fig. A). Reductions in proteinuria observed at month 6 persisted until Month 15, 10 months after the last dose: +6% and −38% mean UPCR change from baseline for placebo and the M3 9-dose arm, respectively (Fig. B). Relatively stable eGFR values were observed for the felza arms compared to loss of eGFR in the placebo arm. Rapid, durable reductions in IgA and Gd-IgA1 levels were seen across the dosing arms, with reductions lasting 10 months after the last dose (Fig. C). IgG recovery occurred faster off-treatment than IgA. Results in the Part 2 subjects were similar to the Part 1 M3 cohort through 9 months. There were no apparent dose-dependent adverse events and no exposure-safety relationship. Treatment-emergent adverse events (TEAEs) were generally of mild or moderate intensity or toxicity grade. The most common TEAE assessed as related by study investigator was infusion related reactions (IRR), most of which occurred on the first infusion. There was one treatment-related serious AE due to an IRR. Five subjects discontinued treatment due to IRRs or drug hypersensitivity; for four of the five subjects, the infusion rate was higher than protocol-specified or had an error in pre-medication. TEAE infections were comparable between placebo and felza arms: Placebo (33.3%), M1 (33.3%), M2 (36.4%), M3 (38.5%), Part 2 (50.0%); all were Grades 1 or 2, and non-serious. Conclusion This proof-of-concept study highlights the potential for disease modification in IgAN with the anti-CD38 mAb felza and supports continued research as a potential treatment for high-risk IgAN patients. Felza treatment resulted in clinically meaningful, prolonged UPCR reductions and eGFR stabilization sustained ≥10 months after dosing was completed. Felza was generally well tolerated with rapid recovery of IgG with durable reductions in IgA and pathogenic Gd-IgA1 levels.

Background and Aims Immunoglobulin A (IgA) nephropathy is the most common primary glomerular disease in the world characterized by the deposition of IgA in the glomeruli. Selective endothelin receptor antagonists have shown positive effects on IgA nephropathy, while certain potential side effects exist. The outcomes of the recent trials need to be confirmed through a combined analysis. Therefore, we aim to assess the efficacy and safety of endothelin receptor antagonists (ERAs) for patients with IgA nephropathy. Method A systematic review and meta-analysis of randomized controlled trials was conducted by systematically searching PUBMED, EMBASE, Web of Science, Cochrane and Clinical Trails databases through January 2025. Study quality was assessed using the Cochrane Collaboration risk-of-bias 2.0 tools. Adults with biopsy-proven IgA nephropathy were included regardless of the use of SGLT2i. The primary outcome was reduction of urine protein to creatinine ratio (UPCR) from baseline. The secondary outcomes included changes in body weight, systolic and diastolic blood pressure (SBP and DBP) from baseline, frequency of treatment emerging adverse events (TEAEs) and safety outcomes of interest. We used Review Manager v.5.4 to pool binary outcomes using risk ratio (RR) and continuous data using mean difference (MD), both with a 95% confidence interval (CI). The protocol was registered in the PROSPERO database (CRD 42024611746). Results Three studies with a total of 875 patients were included. Endothelin receptor antagonists showed a positive impact on improving UPCR compared with placebo or Irbesartan [MD −36.79, 95% CI (−44.93 to −28.65), P &amp;lt; 0.001]. Regarding the effect on adverse events, no significant difference in frequency of TEAEs or serious TEAEs was found. ERAs reduced systolic blood pressure [MD −4.13, 95% CI (−7.94 to −0.33), P = 0.03] and were associated with increased risk of developing hypotension or vasodialation [RR 2.51, 95% CI (1.37 to 4.58), P = 0.003]. There's a higher rate of anemia [RR 2.32, 95% CI (1.29 to 4.17), P = 0.005] and dizziness [RR 2.20, 95% CI (1.24 to 3.89), P = 0.007] in ERAs group. No difference of other adverse effects including fluid retention were found. Conclusion Endothelin receptor antagonists reduce UPCR in IgA patients compared to placebo or Irbesartan, while were associated with increased risk of causing hypotension, anemia and dizziness. Additional evidence from large, well-designed randomized controlled trials and real-world research are urgently needed to further clarify the efficacy and safety of ERAs.

ABSTRACTBackgroundImprovement of proteinuria as a marker for disease activity is associated with a better renal outcome in immunoglobulin A nephropathy (IgAN). Complement is an effector pathway in IgA-mediated kidney injury. Avacopan, a selective C5a receptor inhibitor, has previously shown efficacy in anti-neutrophil cytoplasmic antibody–associated vasculitis. The aim of this study was to evaluate the safety and efficacy of avacopan in patients with IgAN with persistent proteinuria despite a maximally tolerated dose of renin–angiotensin–aldosterone system blockade. The efficacy evaluation was based on the change in proteinuria.MethodsThis open-label pilot trial enrolled adult patients with biopsy-proven IgAN, urinary protein:creatinine ratio (UPCR) >1 g/g creatinine and an estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 or >45 mL/min/1.73 m2 if eGFR has not declined >10 mL/min/1.73 m2 over the previous 24 weeks. If the UPCR remained at >1 g/g creatinine after an 8-week run-in period, patients started avacopan 30 mg twice daily. The primary efficacy endpoint was the change in the slope of the UPCR from the 8-week run-in period to the slope in the 12-week avacopan dosing period.ResultsA total of 10 of 15 screened patients entered the run-in period. Seven patients with a UPCR >1 g/g creatinine received avacopan. Six of seven patients had numerical improvement in the UPCR during the avacopan treatment period, three of whom had a numerical improvement of ∼50% at week 12. At week 24, five of seven patients still showed numerical improvement in the UPCR compared with baseline. The urinary monocyte chemoattractant protein-1:creatinine ratio decreased numerically 30% by week 8, possibly reflecting the anti-inflammatory activity of avacopan. Avacopan was well tolerated. There was one serious adverse event of unstable angina, which was deemed to be unrelated to avacopan.ConclusionsThis short-term pilot study showed an improvement in the slope of the UPCR, with ∼50% improvement in three of seven patients with IgAN. Longer avacopan treatment duration may be indicated for maximal benefit.

Background and Aims IgA nephropathy (IgAN), the most common primary glomerulonephritis and a significant contributor to ESKD worldwide, is characterized by elevated serum levels of galactose-deficient IgA1 (Gd-IgA1). The production of Gd-IgA1 and its autoantibodies is driven by both the B-cell Activating Factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL) signaling pathways that stimulate maturation, differentiation, and effector function of B cells and plasma cells. Atacicept is a fusion protein targeting both BAFF and APRIL in clinical development for IgAN treatment. The Phase 2b ORIGIN study met the primary endpoint with statistically significant urine protein:creatinine ratio (UPCR) reduction at 24 weeks vs placebo. At 36 weeks, atacicept 150 mg achieved statistically significant and clinically meaningful UPCR reduction, eGFR stabilization, and Gd-IgA1 reduction vs placebo, with similar safety to placebo. This interim analysis reports 72-week results from the open-label extension period. Method The randomized, double-blind, placebo-controlled Phase 2b ORIGIN study included 116 participants with biopsy-proven IgAN, 24 h urine protein &amp;gt;0.75 g/day or UPCR &amp;gt;0.75 g/g, and eGFR ≥30 mL/min/1.73 m2 despite optimized renin–angiotensin system blockade. Participants were randomized to atacicept 150, 75, or 25 mg, vs placebo (2:2:1:2), self-administered by subcutaneous injection once weekly for up to 36 weeks. The double-blind randomized treatment period was followed by an open-label extension in which participants could receive atacicept 150 mg for up to 60 additional weeks, for a total of 96 weeks. For this interim analysis, changes from baseline in eGFR, natural log transformed UPCR, and Gd-IgA1 through 72 weeks were analyzed using a mixed-effects model for repeated measurements. Microscopic hematuria was evaluated on urine dipstick and participants with hematuria grade 1+ or higher at baseline were evaluated for resolution, defined as a decrease to negative/trace, at 72 weeks. Results Of 116 randomized participants in the double-blind period, 106 participants (91%) completed 72 weeks of treatment. At 72 weeks, eGFR total slope estimate was 0.0 mL/min/1.73m2/year and eGFR change from baseline was 0 mL/min/1.73m2 in all participants originally randomized to atacicept (all-atacicept group; n = 82). After switching to open-label atacicept 150 mg, the original placebo group showed eGFR stabilization with −3.2 mL/min/1.73m2 change from baseline at 72 weeks vs −4.9 mL/min/1.73m2 at 36 weeks (Figure 1). At 72 weeks, UPCR change from baseline was −45% in the all-atacicept group and the placebo switch group showed a −47% UPCR change from baseline at 72 weeks vs +3% at 36 weeks (Figure 2). Open-label atacicept 150 mg was also associated with rapid Gd-IgA1 reduction in the placebo switch group at 48 weeks that was sustained through 72 weeks. Hematuria resolution was observed at 72 weeks in 81% (35/43) of participants in the all-atacicept group and 59% (10/17) in the placebo switch group. Atacicept was generally well tolerated during the open-label extension, with a similar rate of infections compared to the double-blind period and one study drug-related serious adverse event. Conclusion At 72 weeks, treatment with atacicept 150 mg was associated with sustained eGFR stability and deepening UPCR reductions, as well as a reversal of the downward eGFR decline in the placebo switch group. Sustained reductions in hematuria were also observed. The open-label extension showed a favorable safety profile similar to the double-blind period. These results support atacicept 150 mg as a potential disease-modifying treatment for IgAN.

Background and Aims IgA nephropathy (IgAN) is the most prevalent form of primary glomerulonephritis worldwide and is associated with a poor prognosis, including progression to end-stage kidney disease or death in some cases. Despite recent approvals, an unmet need remains for safe and effective medications. Mezagitamab is a fully human anti-CD38 monoclonal antibody that depletes the plasma cells that produce galactose-deficient IgA1 (Gd-IgA1) and autoantibodies against Gd-IgA1. This mechanism of action is expected to result in decreased immune complex formation, potentially reducing proteinuria and thus promoting stabilization of kidney function over time. Method This open-label, single-arm, phase 1b, multicentre study (NCT05174221), evaluated mezagitamab as an add-on to stable IgAN standard of care therapy. Eligible participants were receiving stable background therapy (angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker) for ≥12 weeks, had biopsy-proven disease, proteinuria assessed by urine protein to creatinine ratio (UPCR) ≥1 mg/mg or urine protein excretion ≥1 g/24 h, and estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2. Participants received subcutaneous mezagitamab 600 mg once weekly for 8 weeks, then 600 mg every 2 weeks for 16 weeks (for a total of 16 doses), followed by a 24-week safety follow-up period. The primary endpoint was percentage of participants with treatment emergent adverse events (AEs). Secondary and exploratory endpoints included serum IgA, Gd-IgA1, and IgG levels, percentage change from baseline in UPCR, and change from baseline in eGFR. This abstract focuses on data from the 48-week visit. Results Seventeen participants enrolled (mean age 40.8 years, 53% female, and 71% Asian). Characteristics at study entry included mean disease duration of 4.6 years, UPCR of 1.5 mg/mg, and eGFR of 74.0 mL/min/1.73 m2. Sixteen (94.1%) participants reported ≥1 AE. There were no serious AEs and no study discontinuations due to AEs. No Grade 3 or higher infections or opportunistic infections were reported. The most common AEs were upper respiratory tract infection (35%), pyrexia (24%), and oropharyngeal pain (24%). At week 48, the reduction from baseline was 52.4% in serum IgA, 57.8% in Gd-IgA1, and 18.9% in IgG. At Week 48, UPCR was reduced from baseline by a mean of 54.1 (95% CI 63.7, 42.0) % (Fig. 1A), and the mean change from baseline in eGFR was +1.1 (95% CI −2.6, +4.8) mL/min/1.73 m2 (Fig. 1B). Conclusion Mezagitamab was generally well tolerated as an add-on to standard of care therapy in IgAN without any opportunistic infections or Grade 3 or higher infections. Rapid and sustained reductions in proteinuria, serum IgA, Gd-IgA1, and IgG were seen while renal function remained stable during the first year of this study. Funding statement The study was funded by Takeda Development Center Americas, Inc., Cambridge, MA, USA.

Targeting the Alternative Complement Pathway With Iptacopan to Treat IgA Nephropathy: Design and Rationale of the APPLAUSE-IgAN Study

Proteinuria and hematuria are both significant predictors of impaired kidney function in IgA nephropathy (IgAN). We evaluated the efficacy and safety of ambrisentan, a selective endothelin A receptor antagonist, as adjunctive therapy in a real-world cohort of high-risk IgAN patients. In this retrospective, single-center study, we analyzed 169 patients with biopsy-proven IgAN who received adjunctive ambrisentan for ≥6 months. A propensity score-matched historical control group (138 pairs) was generated from patients receiving standard care prior to the ambrisentan era. Laboratory test results were gathered at baseline, and at 3 and 6 months. A generalized estimating equation model was employed to adjust for potential confounders. In the full ambrisentan cohort (n = 169), median urinary protein-to-creatinine ratio (UPCR) decreased significantly by 58.4% (95% confidence interval [CI], 49.8-62.3) at 6 months, with 75.7% of patients achieving a ≥30% reduction. Hematuria was also significantly reduced (P < .001), and kidney function remained stable. Compared to the matched controls, the ambrisentan group (n = 138 after propensity score-matching) demonstrated a greater median relative reduction in UPCR (-59.7% vs. -53.7%; P = .015). However, a decrease in hemoglobin levels was observed, with an increased incidence of anemia. The proteinuria-lowering effect was enhanced in patients concurrently receiving angiotensin converting enzyme inhibitors (ACEi)/ angiotensin receptor blockers (ARBs) or finerenone. In this analysis incorporating a matched historical control, adjunctive ambrisentan significantly reduced proteinuria and hematuria in patients with IgAN without affecting kidney function. The proteinuria-lowering effect was more pronounced when ambrisentan was added to an ACEi/ARB or finerenone. Notably, a significant decline in hemoglobin levels was observed, indicating a need for monitoring. These results warrant further prospective trials to confirm the long-term renal benefits and safety of ambrisentan in IgAN.

The role of obesity in the progression of primary glomerular diseases is controversial. A few studies report overweight/obesity as a risk factor for disease progression in immunoglobulin A nephropathy (IgAN), and the real impact of it still remains unclear. The aim of this study was to elucidate the effect of body mass index (BMI) on disease progression and proteinuria in patients with IgAN in Indian population. A cohort of biopsy-proven primary IgAN patients diagnosed between March 2010 and February 2015 who had a follow-up for a minimum of 12 months were included in the study. We defined two groups of patients according to the BMI value at diagnosis: non-obese group (Group N) with BMI <23 Kg/m2 and the overweight/obese group (Group O) with BMI >23 Kg/m2 as per Asia-Pacific task force criteria. Baseline characteristics were compared between the groups. The estimated glomerular filtration rate (eGFR) and urine protein-creatinine ratio (UPCR) were followed up at entry time, 6 months, 12 months, and at the end of follow-up. Outcomes studied were change in eGFR, proteinuria, and progression to end-stage renal disease. Statistical analysis was done using the Statistical Package for the Social Sciences version 15.0. Of 51 patients, 25 (49%) had BMI <23 kg/m2 (Group N) and 26 (51%) had BMI >23 kg/m2 (Group O) (P = 0.01). The baseline clinical, histopathological, and treatment characteristics of both the groups were comparable. The BMI at the time of diagnosis did not have any significant effect on eGFR (P = 0.41) or proteinuria (P = 0.99) at presentation. At the end of follow-up, both the groups had a similar reduction of proteinuria (UPCR) (P = 0.46) and eGFR (P = 0.20). Two patients in each group have reached chronic kidney disease Stage 5. In the present study, BMI at presentation did not have any impact on eGFR or proteinuria, either at diagnosis or at follow-up. It needs further large multicenter randomized control studies to see the effect of BMI on progression of IgAN.

Targeted-release budesonide (TRF-budesonide) is a therapy developed to deliver corticosteroid to ileal Peyer's patches and has demonstrated efficacy in randomized trials (NEFIGAN, NefIgArd) for patients with immunoglobulin A nephropathy (IgAN). We performed a systematic review and meta-analysis to evaluate the efficacy and safety of budesonide formulations in IgAN. We searched PubMed, Embase, and Cochrane through September 10, 2025. Eligible studies assessed budesonide in biopsy-proven IgAN. Outcomes included change in eGFR, percentage and absolute change in urine protein-to-creatinine ratio (UPCR), and adverse events. Random-effects meta-analyses were performed. Nine studies (total N = 465; two RCTs) were included. In the comparative analysis of placebo-controlled trials, TRF-budesonide significantly attenuated eGFR decline compared to placebo (weighted mean difference [WMD] 4.53mL/min/1.73 m2; 95% CI 3.08-5.99). In the single-arm analysis assessing absolute change from baseline, the pooled mean eGFR increase was 3.07mL/min/1.73m2 (95% CI 0.12-6.03). Regarding proteinuria, TRF-budesonide significantly reduced UPCR compared to placebo (percentage change MD - 28.96%; 95% CI - 45.94 to - 11.99). Safety analysis showed budesonide was associated with a higher risk of adverse events versus placebo (RR 1.18; 95% CI 1.01-1.38). In uncontrolled cohorts, pooled adverse event rates were 40% for TRF-budesonide and 44% for enteric-coated formulations. Current evidence indicates that TRF-budesonide improves kidney function and reduces proteinuria in adults with IgAN, but conclusions are tempered by limited RCT data, heterogeneity, short follow-up, and sparse histologic end points. Larger, longer randomized trials with standardized outcomes are needed to confirm long-term benefit and safety.

IgA Nephropathy

Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Background and Aims In immunoglobulin A nephropathy (IgAN), immune complex formation and deposition leads to activation of the complement system. Complement activation leads to glomerular damage and is implicated in tubulointerstitial fibrosis [1]. IgA vasculitis-associated nephritis (IgAVN) is an autoimmune disease with similar pathogenesis to that of IgAN [2]. Currently, there are no approved treatments for children and adolescents with IgAN; treatment recommendations are largely informed by evidence generated in adults [3]. Similarly, there are no treatments specifically for IgAVN. Ravulizumab, a complement C5 inhibitor, is currently approved to treat atypical hemolytic uremic syndrome (including pediatric), paroxysmal nocturnal hemoglobinuria (including pediatric), generalized myasthenia gravis, and neuromyelitis optica spectrum disorder. In a phase 2 trial in adults with IgAN, a rapid and clinically meaningful reduction in proteinuria was observed with ravulizumab [4]. A phase 3 trial of ravulizumab in adults with IgAN (I CAN study, NCT06291376; EU CT 2023-507851-31-00) is ongoing. Here, we describe the design of a phase 3 study of ravulizumab in pediatric patients with IgAN or IgAVN. Method This phase 3, open-label, single-arm, multicenter study evaluates the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of ravulizumab in pediatric patients (N≈18) with IgAN (cohort 1, n = 12) or IgAVN (cohort 2, n ≈ 6). Patients with a diagnosis of IgAN or IgAVN based on kidney biopsy, an estimated glomerular filtration rate (eGFR) of ≥30 mL/min/1.73 m2 during screening, and a urine protein to creatinine ratio (UPCR) of ≥0.5 g/g from first morning void (FMV) during screening will be included (Table 1). The study consists of a 6-week screening, a 34-week primary evaluation, and a 72-week extension period. Patients will receive weight-based loading dose of ravulizumab intravenously on Day 1, followed by weight-based maintenance dose on Day 15, and every 8 weeks (if body weight ≥20 kg) or 4 weeks (if body weight &amp;lt;20 kg) thereafter up to Week 106 (Fig. 1). Formal sample size calculation and statistical hypothesis testing will not be performed due to the descriptive nature of the study. Results The primary endpoints (PK and PD) are ravulizumab maximum serum concentration, trough serum concentration, and change in serum free C5 concentration through Week 34. Secondary endpoints include change from baseline in UPCR up to Week 34, partial remission (≥50% reduction in UPCR from baseline and UPCR &amp;lt;3 g/g) at Week 34, and change from baseline in eGFR up to Week 106. Safety, tolerability, and immunogenicity will also be evaluated. Conclusion IgAN and IgAVN may lead to kidney failure and need for dialysis or transplant if left untreated. This study aims to characterize the PK, PD, efficacy, and safety of ravulizumab in pediatric patients with IgAN or IgAVN. Data from this study could inform future management of these conditions in the pediatric population.