SP323EFFECTS OF RVX-208, A FIRST IN CLASS EPIGENETIC BET INHIBITOR, ON KEY RENAL PARAMETERS IN SUBJECTS WITH A HISTORY OF CVD, AND CHRONIC KIDNEY DISEASE (CKD); A POST-HOC ANALYSIS OF PATIENTS FROM THE ASSERT, SUSTAIN AND ASSURE CLINICAL TRIALS
Bibliographic record
Abstract
Introduction and Aims: RVX-208 is a first in class of orally active small molecules that binds selectively to the second ligand domain of bromodomain extra-terminal proteins (BET). These proteins are epigenetic readers that bind acetylated lysine present in the tail of histones thus affecting chromatin structure. RVX-208 inhibits acetylated lysine from binding to BET proteins and thereby alters activity of selected genes. The epigenetic BET inhibitor RVX-208 is characterized by anti-inflammatory effects, activation of apolipoprotein A-I (apoA-I) transcription and improved metabolic effects. Reductions in alkaline phosphatase (ALP) have also been observed. A subpopulation analysis from the double-blind placebo controlled phase 2b program in cardiovascular disease (CVD) identified 81 subjects with CKD based on eGFR < 60 ml/min/1.73m2. The effect of selective BET inhibition on key renal parameters in this subgroup was assessed. Methods: Total of 81 CKD subjects (RVX-208 n=58/Placebo n=23) were treated with either RVX-200mg b.i.d, RVX-208 300mg b.i.d or matching placebo for 3 months and 48 subjects (RVX-208 n=35/Placebo n=13) were treated with RVX-208 200mg b.i.d or matching placebo for 6 months. A pooled analysis was performed to assess the changes from baseline for eGFR, ALP and creatinine at 3 and 6 months. Additional lipid markers assessed included ApoA-I, HDL-cholesterol and HDL particle parameters by nuclear magnetic resonance (NMR.)
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 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".