A Phase 3 Trial of Atacicept in Patients with IgA Nephropathy
Bibliographic record
Abstract
BACKGROUND: IgA nephropathy, the most common primary glomerulopathy worldwide, is a kidney disorder of B-cell origin characterized by mesangial accumulation of IgA-containing immune complexes. In at least 50% of patients, IgA nephropathy leads to kidney failure or death within 10 to 20 years after diagnosis. Atacicept is a native human transmembrane activator and calcium-modulator and cyclophilin-ligand interactor (TACI)-Fc fusion protein that inhibits two key immunoregulatory cytokines - B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) - that are thought to be central to the pathophysiology of IgA nephropathy. METHODS: In this ongoing, phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients with IgA nephropathy in a 1:1 ratio to receive atacicept at a dose of 150 mg once weekly, administered subcutaneously by patients at home, or matching placebo. The primary end point was the percentage change from baseline in the 24-hour urinary protein-to-creatinine ratio at week 36. Safety was also evaluated. RESULTS: A total of 203 patients were included in the prespecified interim analysis: 106 patients in the atacicept group and 97 in the placebo group. At week 36, the percentage reduction from baseline in the urinary protein-to-creatinine ratio was 45.7% in the atacicept group and 6.8% in the placebo group, with a geometric mean between-group difference of 41.8 percentage points (95% confidence interval, 28.9 to 52.3; P<0.001). Adverse events were observed in 59.3% of the patients in the atacicept group and in 50.0% in the placebo group; most were mild or moderate in severity. CONCLUSIONS: In this prespecified interim analysis, treatment with atacicept resulted in a significantly greater reduction in proteinuria than placebo at week 36 in patients with IgA nephropathy. (Funded by Vera Therapeutics; ORIGIN 3 ClinicalTrials.gov number, NCT04716231.).
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.006 | 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".