VALIANT: Randomized, multicenter, double-blind, placebo-controlled, phase 3 trial of pegcetacoplan for patients with native or post-transplant recurrent C3G or primary (idiopathic) IC-MPGN
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
C3 glomerulopathy (C3G) and primary immune complex-membranoproliferative glomerulonephritis (IC-MPGN) are complement-mediated diseases driven by C3 dysregulation with excessive accumulation of C3 breakdown products in the kidney. Pegcetacoplan (PEG) a C3/C3b inhibitor, targets the central components of the complement pathway, directly inhibiting C3 overactivation and preventing further deposition of C3 breakdown products in the glomeruli. VALIANT (NCT05067127) is the first Phase 3 trial investigating PEG in a broad cohort, including adolescents (≥12 yrs) and adults with native or post-transplant recurrent C3G or primary IC-MPGN. VALIANT is a randomized, multicenter, double-blind, placebo (PBO)-controlled trial evaluating PEG efficacy and safety. 124 pts were randomized to PEG (n = 63) (twice weekly subcutaneous infusion) or PBO (n = 61) for 26 weeks (wks). The primary endpoint was log-transformed UPCR ratio at wk 26 vs baseline, assessing proteinuria reduction vs PBO. Key secondary endpoints at wk 26 were a composite renal endpoint (proportion of pts achieving ≥50% UPCR and ≤15% eGFR decline), proportion of patients achieving ≥50% UPCR reduction, C3G histologic index activity score change (adjusted LS mean change), reduced C3c renal biopsy staining of ≥2 OOM, eGFR change, (LS mean change), mL/min/1.73 m 2 . Safety was assessed by treatment-emergent adverse events (TEAE) frequency and severity. The primary endpoint was met, with PEG demonstrating a 68.1% (95% CI: –76.2, –57.3) mean UPCR reduction vs. PBO at wk 26 (p < 0.0001). Results were consistent across disease type, age, and transplant status subgroups. PEG also led to robust reductions in C3c staining and clinically meaningful eGFR stabilization vs PBO. Treatment-emergent AE frequency and severity were similar between arms. None of the 4 serious infections (3 PEG; 1 PBO) were attributed to encapsulated bacteria. PEG is the first therapy to achieve significant and clinically meaningful reductions in proteinuria (68.1% vs. PBO), C3c staining and eGFR stabilization in pts ≥12 yrs with C3G or primary IC-MPGN. PEG was well tolerated with no new safety signals observed.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it