A randomized phase 1b trial of the active site polymerase inhibitor nucleotide <scp>ATI</scp>‐2173 in patients with chronic hepatitis B virus infection
Bibliographic record
Abstract
Abstract ATI‐2173 is an active site polymerase inhibitor nucleotide in development as part of a potentially curative regimen for chronic hepatitis B virus (HBV) infection. This study evaluated the safety, tolerability, pharmacokinetics (PK) and antiviral activity of ATI‐2173. This was a phase 1b, randomized, double‐blind, placebo‐controlled trial in treatment‐naive adults with chronic HBV infection conducted in the Republic of Moldova and Ukraine ( ClinicalTrials.gov : NCT04248426). Patients positive for hepatitis B surface antigen were randomized 6:2 to receive once‐daily oral doses of ATI‐2173 10, 25, or 50 mg (n = 6 per dose) or placebo (n = 7) for 28 days, with off‐treatment monitoring for 24 weeks. Endpoints included PK parameters of ATI‐2173 and its metabolite clevudine, maximum reduction from baseline in HBV DNA, and safety and tolerability. Treatment‐emergent adverse events occurred in eight patients (47%) receiving ATI‐2173 and five (71%) receiving placebo; headache was the most common (n = 4). ATI‐2173 PK was generally dose proportional. Systemic clevudine exposure with ATI‐2173 dosing was substantially reduced compared with historical values observed with clevudine administration. On Day 28, mean changes from baseline in HBV DNA were −2.72 to −2.78 log10 IU/ml with ATI‐2173 and +0.17 log10 IU/ml with placebo. Off‐treatment sustained viral suppression and decreases in covalently closed circular DNA biomarkers were observed in most patients; one maintained undetectable HBV DNA at 24 weeks off treatment. In this 28‐day monotherapy study, ATI‐2173 demonstrated safety and antiviral activity, with sustained off‐treatment effects and substantially reduced systemic clevudine exposure. These results support evaluation of ATI‐2173 with tenofovir disoproxil fumarate in phase 2 studies.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 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".