ALIGN Subgroup Analyses: Clinically Meaningful Urinary Protein-to-Creatinine Ratio Reductions across Subgroups
Bibliographic record
Abstract
Background: Approximately 30% of IgAN patients (pts) with proteinuria 1–2 g/day develop kidney failure within 10 years; even pts with low levels of persistent proteinuria (<1 g/d) are at risk. Endothelin (ET)-1 upregulation and ETA receptor activation drive proteinuria, kidney inflammation and fibrosis in IgAN. Atrasentan is a potent and selective ETA receptor antagonist. ALIGN is a Phase 3, randomized, double-blind, placebo-controlled study of the efficacy and safety of atrasentan vs placebo in adult IgAN pts on optimized supportive care (SC). Methods: Pts with biopsy-proven IgAN and proteinuria of ≥ 1g/day were randomized to receive atrasentan 0.75 mg or placebo orally once daily for 132 weeks while continuing SC. The primary endpoint, the change from baseline (CFB) in proteinuria at Week 36, based on UPCR from 24-hour urine collection was evaluated in a prespecified interim analysis of the first 270/340 patients randomized to the main stratum. Subgroups evaluated included key demographic (gender, age, race, ethnicity and region), and baseline disease characteristics (baseline UPCR, BP, eGFR and diuretic use). Results: The prespecified interim analysis of the primary endpoint showed a 36.1% (26.4%, 44.6%; p<0.0001) relative reduction in LS mean % UPCR CFB at Week 36. Proteinuria reduction was of similar magnitude regardless of age, sex, race, ethnicity or region, and baseline levels of proteinuria, eGFR, BP or diuretic usage (Fig). Atrasentan was well-tolerated with a favorable safety profile. Results for an exploratory SGLT2i stratum were consistent with the main stratum. Conclusion: Clinically meaningful proteinuria reductions were observed with atrasentan in all subgroups regardless of baseline demographic or disease characteristics. Funding: Commercial Support - Chinook Therapeutics, a Novartis company
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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 | 0.014 |
| Meta-epidemiology (narrow) | 0.002 | 0.000 |
| Meta-epidemiology (broad) | 0.005 | 0.010 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 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) | 0.005 | 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 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".