Wcn26-9116 Efficacy of Pegcetacoplan in Patients With Lower Baseline Proteinuria: A Subgroup Analysis From the Valiant Trial

Q: What is the clinical evidence from this study?

Study design: RCT. Population: C3 glomerulopathy (C3G) and primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN) (n=40). Intervention: Pegcetacoplan vs. Placebo. Primary outcome: Change in log-transformed urine protein-to-creatinine ratio (UPCR) from baseline to Week 26 (Geometric mean ratio 0.288, 95% CI 0.172-0.483).

Seung Hyeok Han; H J Kang; Nicholas Webb; Johan Szamosi; Regina Horneff; K. Gordon; Yiwei Zhang; Eli Khankin; C. Nester

doi:10.1016/j.ekir.2026.106328

March 25, 2026Kidney International ReportsOpen Access

Wcn26-9116 Efficacy of Pegcetacoplan in Patients With Lower Baseline Proteinuria: A Subgroup Analysis From the Valiant Trial

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Key result

Pegcetacoplan reduces proteinuria ~71% vs. placebo at 26 weeks in C3G or IC-MPGN.

Geometric mean ratio 0.288
95% CI 0.172-0.483
n=40

Why the study?

Does pegcetacoplan reduce proteinuria and stabilize eGFR in patients with C3G and IC-MPGN with lower baseline proteinuria?

Key Points

To evaluate the efficacy and safety of pegcetacoplan in patients with C3 glomerulopathy or immune-complex membranoproliferative glomerulonephritis presenting with lower baseline proteinuria.
Post hoc subgroup analysis of the randomized, multicenter, double-blind, placebo-controlled VALIANT trial examining pegcetacoplan versus placebo over 26 weeks.
Included 40 patients with baseline urine protein-to-creatinine ratio (UPCR) ≤1.5 g/g (pegcetacoplan, n=15; placebo, n=25).
Endpoints included change in UPCR and eGFR at Week 26, rates of ≥50% UPCR reduction, and achievement of partial (≤0.5 g/g) or complete (≤0.2 g/g) remission.
At Week 26, pegcetacoplan led to a 71.2% reduction in UPCR compared with placebo, with a geometric mean ratio of 0.288 (95% CI, 0.172 to 0.483).
Significantly more patients receiving pegcetacoplan achieved a ≥50% reduction in UPCR compared to placebo (66.7% [n=10/15] vs 8.0% [n=2/25]; p=0.0012).
Pegcetacoplan achieved higher rates of partial remission (66.7% vs 8.0%) and complete remission (46.7% vs 0.0%) compared to placebo at Week 26.

Study Design

Type

RCT (n=40)

Blinding

Double-blind

Randomization

Randomized

Multicenter

Yes

Structured PICO

Does pegcetacoplan reduce proteinuria and stabilize eGFR in patients with C3G and IC-MPGN with lower baseline proteinuria?

P

Population

40 patients with C3 glomerulopathy or primary immune-complex membranoproliferative glomerulonephritis and baseline proteinuria ≤1.5 g/g, randomized to pegcetacoplan or placebo for 26 weeks.

I

Intervention

Pegcetacoplan subcutaneous infusion twice weekly for 26 weeks

C

Comparator

Placebo for 26 weeks

O

Outcome

Change from baseline to Week 26 in log-transformed urine protein-to-creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR)surrogate

Main Result

Effect estimate: Geometric mean ratio 0.288 (95% CI 0.172-0.483)

In a subgroup analysis of the VALIANT trial, pegcetacoplan significantly reduced proteinuria and stabilized eGFR in patients with C3G and IC-MPGN who had lower baseline proteinuria (≤1.5 g/g).

Limitations

Post hoc analysis
Small sample size in the subgroup

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

Supports pegcetacoplan in lower-proteinuria C3G/IC-MPGN; extends VALIANT RCT findings with consistent efficacy.

Abstract

Conclusion: Clinical efficacy of 52 weeks of pegcetacoplan treatment for adolescents was consistent with the overall population of VALIANT, confirming its sustained benefit in broad patient populations.Previously presented at ASN 2025 (Journal of the American Society of Nephrology) I have potential conflict of interest to disclose.

Discussion

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Cite This Study

Han et al. (2026) conducted an RCT in C3 glomerulopathy (C3G) and primary immune-complex membranoproliferative glomerulonephritis (IC-MPGN) (n=40). Pegcetacoplan vs. Placebo was evaluated on Change in log-transformed urine protein-to-creatinine ratio (UPCR) from baseline to Week 26 (Geometric mean ratio 0.288, 95% CI 0.172-0.483). Pegcetacoplan reduced proteinuria by 71.2% compared to placebo at 26 weeks in patients with C3 glomerulopathy or IC-MPGN and baseline proteinuria ≤1.5 g/g.

synapsesocial.com/papers/69c770418bbfbc51511e0723 https://doi.org/10.1016/j.ekir.2026.106328

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Wcn26-9116 Efficacy of Pegcetacoplan in Patients With Lower Baseline Proteinuria: A Subgroup Analysis From the Valiant Trial

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Wcn26-9116 Efficacy of Pegcetacoplan in Patients With Lower Baseline Proteinuria: A Subgroup Analysis From the Valiant Trial

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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