Efficacy and Safety of Ravulizumab in IgAN: Week 50 Results from a Phase 2 Randomized Controlled Trial
Bibliographic record
Abstract
Background: In IgA nephropathy (IgAN), terminal complement pathway activation contributes to inflammation and glomerular damage. Early and meaningful reductions in proteinuria were demonstrated with complement C5 inhibitor ravulizumab (RAV) in the phase 2 SANCTUARY trial (NCT04564339) through 26wks; efficacy and safety data through 50wks are presented. Methods: Adults with primary IgAN, proteinuria ≥1 g/d, eGFR ≥30 mL/min/1.73 m2, and on stable/optimal RASi were randomized 2:1 to RAV or placebo (PBO) (IV; q8w) for 26wks. At wk26, PBO group switched to open label RAV (PBO-RAV). Primary endpoint: change in proteinuria at 26wks; secondary endpoints: change in proteinuria and eGFR at 50wks. Safety and PK/PD were assessed. Results: Of 66 randomized patients (pts; RAV n=43; PBO n=23), 64 completed wk50. In RAV and PBO arms, respective baseline (BL) UPCR was 1.7 and 1.8 g/g; BL eGFR was 76.0 and 70.4 mL/min/1.73 m2. At 26wks, a –33.2% treatment effect on UPCR was demonstrated with RAV vs PBO (p=0.0011). At 50wks, RAV pts had a 41.1% reduction from BL in UPCR. PBO-RAV pts had a 43.1% decrease in UPCR from BL (wk0) to wk50 (Figure). Annualized eGFR slope in RAV pts was –1.4 at 26wks and –2.3 at 50wks and in PBO-RAV pts was –6.7 and –4.1 at 26 and 50wks, respectively. The majority of AEs were mild; no serious treatment-related AEs, discontinuations from AEs, or deaths occurred. Conclusion: Treatment with RAV was well-tolerated and demonstrated early and sustained proteinuria reduction through ~1 year, and after wk26 switch from PBO to RAV. Funding: Commercial Support - Alexion, AstraZeneca Rare Disease
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.003 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".