#123 Impact of atacicept on hematuria in IGA nephropathy: post-hoc analysis of the phase 2b ORIGIN study
Bibliographic record
Abstract
Abstract Background and Aims Patients with IgA nephropathy (IgAN) and persistent hematuria during follow up have a greater decline in renal function than those with minimal or no hematuria, while hematuria resolution has been independently associated with less decline in renal function [1, 2]. Atacicept is a fusion protein targeting both BAFF and APRIL in clinical development for IgAN. The Phase 2b ORIGIN study met the primary endpoint with statistically significant urine protein:creatinine ratio (UPCR) reduction at 24 weeks for atacicept vs placebo. At 36 weeks, atacicept 150 mg achieved statistically significant and clinically meaningful UPCR reduction, eGFR stabilization, and robust reduction of galactose-deficient IgA1 vs placebo, with similar safety to placebo. This post-hoc analysis evaluates changes in hematuria during treatment with atacicept vs placebo over 36 weeks. Method The randomized, double-blind, placebo-controlled Phase 2b ORIGIN study included 116 participants with biopsy-proven IgAN, 24h urine protein >0.75 g/day or UPCR >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. Microscopic hematuria was evaluated at weeks 2, 4, 12, 24, and 36 via urine dipstick at a centralized lab, and hematuria levels were graded negative/trace, 1+, 2+, or 3+. Hematuria improvement was defined as a decrease by ≥1 grade, and resolution was defined as a decrease to negative/trace. Results In the intent-to-treat population, 15 of 33 (45%) participants who received atacicept 150 mg and 19 of 34 (56%) who received placebo had hematuria (1+ or greater) at baseline. Of these, 87% (n = 13/15) on atacicept 150 mg had improved hematuria at 36 weeks vs 32% (n = 6/19) on placebo (p = 0.002), with 80% (n = 12/15) on atacicept 150 mg achieving resolution to negative/trace hematuria vs 5% (n = 1/19) on placebo (p < 0.0001) (Figure). The atacicept 150 mg group steadily improved to lower hematuria grades over 36 weeks, with improvement occurring as early as 4 weeks, while the placebo group had no improvement in hematuria over time. The majority of participants without hematuria at baseline maintained negative or trace levels at 36 weeks. Conclusion In a post-hoc analysis, atacicept treatment was associated with hematuria resolution at 36 weeks in a substantially greater percentage of participants as compared with placebo, with improvements seen as early as 4 weeks. These results add to the growing body of evidence supporting atacicept as a potential disease-modifying treatment for IgAN. Atacicept 150 mg is currently being evaluated in a global Phase 3 randomized placebo-controlled trial.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.014 | 0.007 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.005 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".