RNA interference targeting ANGPTL3 for triglyceride and cholesterol lowering: phase 1 basket trial cohorts
Bibliographic record
Abstract
Abstract Elevated triglycerides and non-high-density lipoprotein cholesterol (HDL-C) are risk factors for atherosclerotic cardiovascular disease (ASCVD). ARO-ANG3 is an RNA interference therapy that targets angiopoietin-like protein 3 (ANGPTL3), a regulator of lipoprotein metabolism. This first-in-human, phase 1, randomized, placebo-controlled, open-label trial investigated single and repeat ARO-ANG3 doses in four cohorts of fifty-two healthy participants and one cohort of nine participants with hepatic steatosis, part of a basket trial. Safety (primary objective) and pharmacokinetics (in healthy participants) and pharmacodynamics (secondary objectives) of ARO-ANG3 were evaluated. ARO-ANG3 was generally well tolerated, with similar frequencies of treatment-emergent adverse events in active and placebo groups. Systemic absorption of ARO-ANG3 in healthy participants was rapid and sustained, with a mean T max of 6.0–10.5 h and clearance from plasma within 24–48 h after dosing with a mean t ½ of 3.9–6.6 h. In healthy participants, ARO-ANG3 treatment reduced ANGPTL3 (mean −45% to −78%) 85 days after dose. Reductions in triglyceride (median −34% to −54%) and non-HDL-C (mean −18% to −29%) (exploratory endpoints) concentrations occurred with the three highest doses. These early-phase data support ANGPTL3 as a potential therapeutic target for ASCVD treatment. ClinicalTrials.gov identifier: NCT03747224
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| 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".