Sibeprenlimab in IgA Nephropathy — Interim Analysis of a Phase 3 Trial
Bibliographic record
Abstract
BACKGROUND: The cytokine A proliferation-inducing ligand (APRIL) is considered a key driver of the pathogenesis of IgA nephropathy. Sibeprenlimab, a humanized IgG2 monoclonal antibody, selectively binds to and inhibits APRIL. METHODS: In this phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned adults with biopsy-confirmed IgA nephropathy in a 1:1 ratio to receive either subcutaneous sibeprenlimab at a dose of 400 mg or placebo administered every 4 weeks for 100 weeks. The primary end point for this interim analysis was the 24-hour urinary protein-to-creatinine ratio at 9 months as compared with baseline. The key secondary end point, to be reported at trial completion, is the annualized slope of estimated glomerular filtration rate over 24 months. Other secondary end points included the change in the level of serum immunoglobulin and safety. Exploratory end points included the change in galactose-deficient IgA1 and APRIL concentrations, the spot 24-hour urinary protein-to-creatinine ratio, hematuria, and remission of proteinuria. RESULTS: A total of 510 patients underwent randomization - 259 to the sibeprenlimab group and 251 to the placebo group. The prespecified interim analysis included the first 320 patients (152 who received sibeprenlimab and 168 who received placebo) who had the opportunity to complete the 9-month evaluation of the 24-hour urinary protein-to-creatinine ratio. At 9 months, a significant reduction in 24-hour urinary protein-to-creatinine ratio was observed with sibeprenlimab (-50.2%) as compared with an increase with placebo (2.1%), corresponding to an adjusted geometric least-squares mean 24-hour urinary protein-to-creatinine ratio that was 51.2% (96.5% confidence interval [CI], 42.9 to 58.2) lower with sibeprenlimab than with placebo (P<0.001). The levels of APRIL and pathogenic galactose-deficient IgA1 at week 48 were reduced from baseline by 95.8% and 67.1%, respectively, with sibeprenlimab. The safety profile appeared to be similar with sibeprenlimab and placebo. No deaths were reported, and the incidence of serious adverse events that occurred during the treatment period was 3.5% with sibeprenlimab and 4.4% with placebo. CONCLUSIONS: Sibeprenlimab resulted in a significant reduction in proteinuria as compared with placebo in patients with IgA nephropathy. (Funded by Otsuka Pharmaceutical Development and Commercialization. VISIONARY ClinicalTrials.gov number, NCT05248646.).
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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 | 0.010 | 0.006 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.005 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 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".