25-LB: Oral APX3330 Reduces the DRSS Worsening after 24-weeks of Daily Treatment—Efficacy and Safety Results of the ZETA-1 Phase 2 Trial in Diabetic Retinopathy
Bibliographic record
Abstract
APX3330 is an oral, novel, small-molecule inhibitor of Ref-1, in diabetic retinopathy (DR) patients. ZETA-1 was a multi-center, placebo-controlled, double-masked Phase 2 trial. Subjects were randomized 1:1 to receive APX3330 (total 600 mg/day) or placebo BID for 24 weeks. Eligible subjects had non-proliferative DR (NPDR) or mild proliferative DR, corresponding to DR severity scale (DRSS) scores of 47, 53, or 61 as confirmed by the Duke reading center. The primary efficacy endpoint was the % of subjects with ≥ 2-step DRSS improvement in the study eye at week 24 compared to baseline. Several key pre-specified endpoints were evaluated. Results: ZETA-1 trial enrolled 103 DR subjects with 90% having NPDR with a baseline DRSS of 47 or 53. The primary endpoint was not met with 8% of study eyes showing ≥ 2-step DRSS improvement in each treatment group. Consistent with its mechanism of action of bringing VEGF and inflammation to physiologic levels, APX3330 demonstrated a statistically significant reduction in binocular ≥ 3-step worsening after 24 weeks, with 16% of placebo subjects worsening compared to 0% of APX3330 subjects (p=0.04). 19% of placebo subjects lost ≥5 BCVA letters compared to 5% of APX3330 subjects (p=0.07). AEs that occurred in ≥5% of subjects were pruritis, rash, and worsening of DR or DME in the placebo group. No subjects withdrew due to rash or pruritis. Disclosure V. H. Gonzalez: Consultant; Alimera, Bausch + Lomb, Research Support; Adverum Biotechnologies, AbbVie Inc., Apellis, Genentech, Inc., IQVIA Inc., Iveric Bio, Regeneron. P. K. Kaiser: Consultant; Ocuphire, AbbVie Inc., Bausch + Lomb, Bayer Inc., Regeneron, Ocular Therapeutix, Novartis, REGENXBIO Inc. D. S. Boyer: Advisory Panel; 3Boehringer Ingelheim Canada Ltd. /Ltée, AbbVie Inc., Adverum Biotechnologies, Alexion Pharmaceuticals, Inc., Alkahest, Allergan, Amgen Inc., Apellis, Bausch + Lomb, Chengdu Pharmaceuticals, F. Hoffmann-La Roche Limited, Genentech, Inc., Iveric Bio, Gyroscope, Janssen Pharmaceuticals, Inc., Kodiak Pharmaceuticals, NGM Biopharmaceuticals, Oxurion, Novartis, ocuphire, Roche Pharmaceuticals, REGENXBIO Inc., Other Relationship; 4D Pharma PLC. M. G. Brigell: Consultant; Ocuphire Pharma, ONL Therapeutics. D. Su: None. R. Patel: Employee; Ocuphire Pharma. B. Withers: Employee; Ocuphire. M. Kelley: None. L. Haddad: None. M. Sooch: Board Member; Ocuphire Pharma, Employee; Ocuphire Pharma, Stock/Shareholder; Ocuphire Pharma. J. S. Pepose: Consultant; Acufocus, Bausch + Lomb, Brim Biotechnology, Johnson & Johnson Medical Devices Companies, Kala Pharmaceuticals, Mimetogen, Ocuphire Pharma, OKYO Pharma, Stuart Therapeutics, Thea Pharma.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".