ORIGIN 3: A Phase 3 Trial of Atacicept in IgAN
Bibliographic record
Abstract
Background: IgA nephropathy (IgAN) is a B-cell mediated immune complex glomerulonephritis. Atacicept is a native human TACI-Fc fusion protein that binds and inhibits B-cell Activating Factor (BAFF) and A PRoliferation-Inducing Ligand (APRIL), key immunoregulatory cytokines central to the pathophysiology of IgAN, thereby modulating B-cell activity. Methods: In this ongoing double-blind, placebo-controlled, multinational Phase 3 trial, patients with biopsy-proven IgAN were randomized 1:1 to 150 mg of atacicept, self-administered subcutaneously once weekly at home, or placebo. The primary endpoint was percentage change from baseline (BL) at Week 36 in the urinary protein-to-creatinine ratio (UPCR) from a 24-hour collection. Secondary endpoints of galactose-deficient IgA1 (Gd-IgA1) percentage change from BL, hematuria resolution, and safety were also evaluated. Results: The interim analysis included 203 patients (atacicept n=106; placebo n=97). At Week 36, atacicept treatment resulted in a 45.7% UPCR reduction from BL vs. a 6.8% reduction with placebo, with a statistically significant 41.8% (95% CI, 28.9%–52.3%; P<0.0001) treatment difference (Figure). Significant improvements were also observed in Gd-IgA1 and hematuria with atacicept (Figure). The incidence of adverse events was similar between both groups, and most were mild or moderate. Conclusion: Atacicept treatment resulted in a statistically significant proteinuria reduction compared with placebo at Week 36, as well as Gd-IgA1 reduction, hematuria improvement, and a favorable safety profile. The results demonstrate the potential for atacicept to address the underlying pathophysiology of IgAN and provide a targeted, disease-modifying therapy. Funding: Commercial Support - Vera Therapeutics, Inc.
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How this classification was reachedexpand
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) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".